ORCID Profile
0000-0003-1785-3491
Current Organisations
Universitas Pattimura
,
National Research and Innovation Agency
,
Queensland University of Technology
,
Griffith University
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Publisher: Elsevier
Date: 2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9TB90066G
Abstract: Correction for ‘Nutrient element-based bioceramic coatings on titanium alloy stimulating osteogenesis by inducing beneficial osteoimmmunomodulation’ by Zetao Chen et al. , J. Mater. Chem. B , 2014, 2 , 6030–6043.
Publisher: American Chemical Society (ACS)
Date: 20-02-2019
Publisher: American Chemical Society (ACS)
Date: 11-12-2019
Publisher: The Royal Society
Date: 25-05-2011
Abstract: The efficient loading and sustained release of proteins from bioactive microspheres remain a significant challenge. In this study, we have developed bioactive microspheres which can be loaded with protein and then have a controlled rate of protein release into a surrounding medium. This was achieved by preparing a bioactive microsphere system with core-shell structure, combining a calcium silicate (CS) shell with an alginate (A) core by a one-step in situ method. The result was to improve the microspheres' protein adsorption and release, which yielded a highly bioactive material with potential uses in bone repair applications. The composition and the core-shell structure, as well as the formation mechanism of the obtained CS–A microspheres, were investigated by X-ray diffraction, optical microscopy, scanning electron microscopy, energy dispersive spectrometer dot and line-scanning analysis. The protein loading efficiency reached 75 per cent in CS–A microspheres with a core-shell structure by the in situ method. This is significantly higher than that of pure A or CS–A microspheres prepared by non- in situ method, which lack a core-shell structure. CS–A microspheres with a core-shell structure showed a significant decrease in the burst release of proteins, maintaining sustained release profile in phosphate-buffered saline (PBS) at both pH 7.4 and 4.3, compared with the controls. The protein release from CS–A microspheres is predominantly controlled by a Fickian diffusion mechanism. The CS–A microspheres with a core-shell structure were shown to have improved apatite-mineralization in simulated body fluids compared with the controls, most probably owing to the existence of bioactive CS shell on the surface of the microspheres. Our results indicate that the core-shell structure of CS–A microspheres play an important role in enhancing protein delivery and mineralization, which makes these composite materials promising candidates for application in bone tissue regeneration.
Publisher: American Chemical Society (ACS)
Publisher: American Association for the Advancement of Science (AAAS)
Date: 2020
Abstract: Stenting is currently the major therapeutic treatment for cardiovascular diseases. However, the nonbiogenic metal stents are inclined to trigger a cascade of cellular and molecular events including inflammatory response, thrombogenic reactions, smooth muscle cell hyperproliferation accompanied by the delayed arterial healing, and poor reendothelialization, thus leading to restenosis along with late stent thrombosis. To address prevalence critical problems, we present an endothelium-mimicking coating capable of rapid regeneration of a competently functioning new endothelial layer on stents through a stepwise metal (copper)-catechol-(amine) (MCA) surface chemistry strategy, leading to combinatorial endothelium-like functions with glutathione peroxidase-like catalytic activity and surface heparinization. Apart from the stable nitric oxide (NO) generating rate at the physiological level ( 2.2 × 10 − 10 mol / c m 2 / min lasting for 60 days), this proposed strategy could also generate abundant amine groups for allowing a high heparin conjugation efficacy up to ∼1 μ g/cm 2 , which is considerably higher than most of the conventional heparinized surfaces. The resultant coating could create an ideal microenvironment for bringing in enhanced anti-thrombogenicity, anti-inflammation, anti-proliferation of smooth muscle cells, re-endothelialization by regulating relevant gene expressions, hence preventing restenosis in vivo. We envision that the stepwise MCA coating strategy would facilitate the surface endothelium-mimicking engineering of vascular stents and be therefore helpful in the clinic to reduce complications associated with stenosis.
Publisher: Hindawi Limited
Date: 29-10-2020
DOI: 10.1155/2020/8865499
Abstract: Numerous biological processes are regulated by the intercellular communications arising from extracellular vesicles (EVs) released from cells. However, the mechanisms that regulate the quantity of EV discharged have yet to be understood. While it is known that ATP9A, a P4-ATPase, is involved in endosomal recycling, it is not clear whether it also contributes to the release of EVs and the makeup of exosomal lipids. This study is aimed at exploring the role of human ATP9A in the process of EV release and, further, to analyze the profiles of EV lipids regulated by ATP9A. Our results demonstrate that ATP9A is located in both the intracellular compartments and the plasma membrane. The percentage of ceramides and sphingosine was found to be significantly greater in the control cells than in the ATP9A overexpression and ATP9A knockout groups. However, EV release was greater in ATP9A knockout cells, indicating that ATP9A inhibits the release of EVs. This study revealed the effects of ATP9A on the release of EVs and the lipid composition of exosomes.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.BIOMATERIALS.2009.09.013
Abstract: To enhance and regulate cell affinity for poly (L-lactic acid) (PLLA) based materials, two hydrophilic ligands, poly (ethylene glycol) (PEG) and poly (L-lysine) (PLL), were used to develop triblock copolymers: methoxy-terminated poly (ethylene glycol)-block-poly (L-lactide)-block-poly (L-lysine) (MPEG-b-PLLA-b-PLL) in order to regulate protein absorption and cell adhesion. Bone marrow stromal cells (BMSCs) were cultured on different composition of MPEG-b-PLLA-b-PLL copolymer films to determine the effect of modified polymer surfaces on BMSC attachment. To understand the molecular mechanism governing the initial cell adhesion on difference polymer surfaces, the mRNA expression of 84 human extracellular matrix (ECM) and adhesion molecules was analysed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). It was found that down regulation of adhesion molecules was responsible for the impaired BMSC attachment on PLLA surface. MPEG-b-PLLA-b-PLL copolymer films improved significantly the cell adhesion and cytoskeleton expression by upregulation of relevant molecule genes significantly. Six adhesion genes (CDH1, ITGL, NCAM1, SGCE, COL16A1, and LAMA3) were most significantly influenced by the modified PLLA surfaces. In summary, polymer surfaces altered adhesion molecule gene expression of BMSCs, which consequently regulated cell initial attachment on modified PLLA surfaces.
Publisher: InTech
Date: 15-09-2011
DOI: 10.5772/23071
Publisher: Elsevier BV
Date: 03-2020
Publisher: American Chemical Society (ACS)
Date: 07-08-2019
DOI: 10.1021/ACS.NANOLETT.9B01459
Abstract: Sensory neurons promote profound suppressive effects on neutrophils during
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4TB00009A
Abstract: Most research virtually ignores the important role of a blood clot in supporting bone healing.
Publisher: Spandidos Publications
Date: 07-2015
Publisher: Wiley
Date: 04-2010
DOI: 10.1111/J.1600-0714.2009.00831.X
Abstract: The temporomandibular joint (TMJ) cartilage consists of condylar cartilage and disc and undergoes continuous remodeling throughout post-natal life. To maintain the integrity of the TMJ cartilage, anti-angiogenic factors play an important role during the remodeling process. In this study, we investigated the expression of the anti-angiogenic factor, chondromodulin-1 (ChM-1), in TMJ cartilage and evaluate its potential role in TMJ remodeling. Eight TMJ specimens were collected from six 4-month-old Japanese white rabbits. Safranin-O staining was performed to determine proteoglycan content. ChM-1 expression in TMJ condylar cartilage and disc was determined by immunohistochemistry. Three human perforated disc tissue s les were collected for investigation of ChM-1 and vascular endothelial growth factor (VEGF) distribution in perforated TMJ disc. Safranin-O stained weakly in TMJ compared with tibial articular and epiphyseal cartilage. In TMJ, ChM-1 was expressed in the proliferative and hypertrophic zone of condylar cartilage and chondrocyte-like cells in the disc. No expression of ChM-1 was observed in osteoblasts and subchondral bone. ChM-1 and VEGF were both similarly expressed in perforated disc tissues. ChM-1 may play a role in the regulation of TMJ remodeling by preventing blood vessel invasion of the cartilage, thereby maintaining condylar cartilage and disc integrity.
Publisher: Wiley
Date: 20-03-2020
Publisher: Wiley
Date: 10-05-2006
Publisher: Wiley
Date: 2000
Abstract: The levels of glycosaminoglycans in gingival crevicular fluid (GCF) are good indicators of underlying tissue turnover. We hypothesize that connective tissue elements in GCF may be used as indicators of tissue maturation underneath barrier membranes. Therefore, we investigated the levels of sulfated glycosaminoglycans in GCF at sites before and after guided tissue regeneration (GTR). Six patients were selected on the basis of having at least one Class II buccal furcation involvement on a molar tooth. Each molar furcation was treated with the standard GTR surgical protocol using a non-resorbable expanded polytetrafluoroethylene membrane. Gingival crevicular fluid s les were taken at baseline (immediately prior to insertion of the membrane) and at 1, 2, 3, 4, 5, and 6 weeks (immediately prior to removal of the membrane). Glycosaminoglycan levels were determined using an Alcian blue dye detection system. The mean levels of chondroitin sulfate and total sulfated glycosaminoglycans in GCF significantly decreased during the first 4 weeks after GTR surgery. By week 5, the levels began to rise, and by week 6 the levels had returned to baseline levels. Sulfated glycosaminoglycans can be monitored in GCF at healing GTR sites. It is proposed that this is a useful means of monitoring the status of the regenerating tissues. However, further longitudinal studies are required to assess if the sulfated glycosaminoglycans can be used as indicators of tissue maturation under guided tissue membranes used to treat periodontal defects.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.ACTBIO.2018.06.023
Abstract: Coating materials applied for intraosseous implants must be optimized to stimulate osseointegration. Osseointegration is a temporal and spatial physiological process that not only requires interactions between osteogenesis and angiogenesis but also necessitates a favorable immune microenvironment. It is now well-documented that hierarchical nano-micro surface structures promote the long-term stability of implants, the interactions between nano-micro structure and the immune response are largely unknown. Here, we report the effects of microporous titanium (Ti) surfaces coated with nano-hydroxyapatite (HA) produced by micro-arc oxidation and steam-hydrothermal treatment (SHT) on multiple cell behavior and osseointegration. By altering the processing time of SHT it was possible to shift HA structures from nano-particles to nano-rods on the microporous Ti surfaces. Ti surfaces coated with HA nano-particles were found to modulate the inflammatory response resulting in an osteoimmune microenvironment more favorable for osteo-/angio-genesis, most likely via the activation of certain key signaling pathways (TGF-β, OPG/RANKL, and VEGF). By contrast, Ti surfaces coated with nano-rod shaped HA particles had a negative impact on osteo-/angio-genesis and osteoimmunomodulation. In vivo results further demonstrated that Ti implant surfaces decorated with HA nano-particles can stimulate new bone formation and osseointegration with enhanced interaction between osteocytes and implant surfaces. This study demonstrated that Ti implants with micro-surfaces coated with nano-particle shaped HA have a positive impact on osseointegration. Osteo-/angio-genesis are of importance during osteointegration of the implants. Recent advances unravel that immune response of macrophages and its manipulated osteoimmunomodulation also exerts a pivotal role to determine the fate of the implant. Surface nano-micro modification has evidenced to be efficient to influence osteogenesis, however, little is known links nano-microstructured surface to immune response, as well the osteoimmunomodulation. This study demonstrates that the nano-particles decorated micro-surface, compared with the nano-rods decorated micro-surface enables osteogenesis and angiogenesis concurrently that has not been investigated previously. This study also unravels that the immune response of macrophages can be manipulated by the nano-micro surface, especially the nano-dimension matters, leading to a differential effect on osteointegration. The additional knowledge obtained from this study may provide foundation and reference for future design of the coating materials for implantable materials.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4TB00837E
Abstract: Nutrient element-based Sr 2 ZnSi 2 O 7 coatings induce favorable osteoimmunomodulation. Material chemistry of Sr 2 ZnSi 2 O 7 coating modulates the immune environment to induce osteogenic differentiation of BMSCs by activating BMP2 signalling pathway.
Publisher: Elsevier BV
Date: 03-2021
Publisher: American Chemical Society (ACS)
Date: 08-03-2018
Abstract: The treatment of melanoma requires complete removal of tumor cells and simultaneous tissue regeneration of tumor-initiated cutaneous defects. Herein, copper silicate hollow microspheres (CSO HMSs)-incorporated bioactive scaffolds were designed for chemo-photothermal therapy of skin cancers and regeneration of skin tissue. CSO HMSs were synthesized with interior hollow and external nanoneedle microstructure, showing excellent drug-loading capacity and photothermal effects. With incorporation of drug-loaded CSO HMSs into the electrospun scaffolds, the composite scaffolds exhibited excellent photothermal effects and controlled NIR-triggered drug release, leading to distinctly synergistic chemo-photothermal therapy of skin cancer both in vitro and in vivo. Furthermore, such CSO HMSs-incorporated scaffolds could promote proliferation and attachment of normal skin cells and accelerate skin tissue healing in tumor-bearing and diabetic mice. Taken together, CSO HMSs-incorporated scaffolds may be used for complete eradication of the remaining tumor cells after surgery and simultaneous tissue healing, which offers an effective strategy for therapy and regeneration of tumor-initiated tissue defects.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1038/LABINVEST.2017.117
Abstract: Of the many cell-based treatments that have been tested in an effort to regenerate osteoarthritic articular cartilage, none have ever produced cartilage that compare with native hyaline cartilage. Studies show that different cell types lead to inconsistent results and for cartilage regeneration to be considered successful, there must be an absence of fibrotic tissue. Here we report of a series of experiments in which bone marrow-derived stem cells (BMSCs) and articular cartilage chondrocytes (ACCs) were mixed in a 1:1 ratio and tested for their ability to enhance cartilage regeneration in three different conditions: (1) in an in vitro differentiation model (2) in an ex vivo cartilage defect model implanted subcutaneously in mice and (3) as an intra-articular injection in a meniscectomy-induced OA model in rats. The mixed cells were compared with monocultures of BMSCs and ACCs. In all three experimental models there was significantly enhanced cartilage regeneration and decreased fibrosis in the mixed BMSCs+ACCs group compared with the monocultures. Molecular analysis showed a reduction in vascularization and hypertrophy, coupled with higher chondrogenic gene expression resulting from the BMSCs+ACCs treatment. Together, our data suggest that mixed BMSCs+ACCs treatment is highly chondro-protective and is more effective in regenerating damaged cartilage in both the ex vivo cartilage defect and post-trauma OA disease models. The results from this approach could potentially be used for regeneration of cartilage in OA patients.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2017
DOI: 10.1038/SREP46457
Abstract: The predominant saturated fatty acids (SFA) in human diets are lauric acid (LA, C12:0), myristic acid (MA, C14:0), palmitic acid (PA, C16:0) and stearic acid (SA, C18:0). The aim of this study was to investigate whether diets containing in idual SFA together with excess simple carbohydrates induce osteoarthritis (OA)-like changes in knee joints and signs of metabolic syndrome in rats. Rats were given either a corn starch diet or a diet composed of simple carbohydrates together with 20% LA, MA, PA, SA or beef tallow for 16 weeks. Rats fed beef tallow, SA, MA or PA diets developed signs of metabolic syndrome, and also exhibited cartilage degradation and subchondral bone changes similar to OA. In contrast, replacement of beef tallow with LA decreased signs of metabolic syndrome together with decreased cartilage degradation. Furthermore, PA and SA but not LA increased release of matrix sulphated proteoglycans in cultures of bovine cartilage explants or human chondrocytes. In conclusion, we have shown that longer-chain dietary SFA in rats induce both metabolic syndrome and OA-like knee changes. Thus, diets containing SFA are strongly relevant to the development or prevention of both OA and metabolic syndrome.
Publisher: Oxford University Press (OUP)
Date: 12-01-2012
DOI: 10.1093/RHEUMATOLOGY/KER360
Abstract: The p38 mitogen-activated protein kinase (MAPK) signal transduction pathway is involved in a variety of inflammatory responses, including cytokine generation, cell differentiation proliferation and apoptosis. Here, we examined the effects of systemic p38 MAPK inhibition on cartilage cells and OA disease progression by both in vitro and in vivo approaches. p38 kinase activity was evaluated in normal and OA cartilage cells by measuring the amount of phosphorylated protein. To examine the function of p38 signalling pathway in vitro, normal chondrocytes were isolated and differentiated in the presence or absence of p38 inhibitor SB203580 and analysed for chondrogenic phenotype. Effect of systemic p38 MAPK inhibition in normal and OA (induced by menisectomy) rats were analysed by treating animals with vehicle alone [dimethylsulphoxide (DMSO)] or p38 inhibitor (SB203580). Damage to the femur and tibial plateau was evaluated by modified Mankin score, histology and immunohistochemistry. Our in vitro studies have revealed that a down-regulation of chondrogenic and an increase of hypertrophic gene expression occurs in the normal chondrocytes when p38 is neutralized by a pharmacological inhibitor. We further observed that the basal levels of p38 phosphorylation were decreased in OA chondrocytes compared with normal chondrocytes. These findings together indicate the importance of this pathway in the regulation of cartilage physiology and its relevance to OA pathogenesis. At the in vivo level, systematic administration of a specific p38 MAPK inhibitor, SB203580, continuously for more than a month led to a significant loss of proteoglycan, aggrecan and cartilage thickness. On the other hand, SB203580-treated normal rats showed a significant increase in Terminal dUTP nick end-labelling (TUNEL)-positive cells, cartilage hypertrophy markers such as Type 10 collagen, Runt-related transcription factor and MMP-13 and substantially induced OA-like phenotypic changes in the normal rats. In addition, menisectomy-induced OA rat models that were treated with p38 inhibitor showed aggravation of cartilage damage. In summary, this study has provided evidence that the component of the p38 MAPK pathway is important to maintain cartilage health, and its inhibition can lead to severe cartilage degenerative changes. The observations in this study highlight the possibility of using activators of the p38 pathway as an alternative approach in the treatment of OA.
Publisher: Wiley
Date: 11-1996
DOI: 10.1902/JOP.1996.67.11.1233
Abstract: In the present study histochemical techniques were used to identify specific macromolecular components of the extracellular matrix associated with the tissue reaction to demineralized freeze-dried bone allografts (DFDBA) placed under barrier membranes for ridge augmentation. Small biopsies were obtained from tissues underneath the membranes at various times after placement of the DFDBA and processed for routine immunohistochemistry. Sections were stained with antibodies to osteocalcin, collagen type I, collagen type III, decorin, and biglycan. Non-immune serum, irrelevant antibodies, and omission of the primary antibodies served as negative controls. Histologic examination of the biopsies revealed allograft particles surrounded by well-formed fibrous connective tissue with little or no evidence of new bone formation. Vital autogenous bone fragments were present in the peripheral portions of the biopsies and served as positive controls for comparative purposes with the DFDBA particles. Only 7 out of the 20 biopsies studied were found to have any signs of bone formation around the DFDBA particles and in these such bone formation was irregular and inconsistent around the DFDBA particles. Around the periphery of the allograft particles, osteocalcin, collagen type I, collagen type III, decorin, and biglycan all showed relatively strong staining. Osteocalcin staining was also noted within the vital bone matrix but not in the surrounding fibrous connective tissue. Decorin, biglycan, collagen type I, and collagen type III were also found within the vital bone matrix. None of these antibodies stained the DFDBA particles. The unremarkable osteogenic response of the tissues to the DFDBA particles after healing periods of up to 12 months raises questions as to the predictability of these agents in inducing new bone.
Publisher: Wiley
Date: 04-03-2023
Abstract: The treatment of irregular bone defects remains a clinical challenge since the current biomaterials (e.g., calcium phosphate bone cement (CPC)) mainly act as inert substitutes, which are incapable of transforming into a regenerated host bone (termed functional bone regeneration). Ideally, the implant degradation rate should adapt to that of bone regeneration, therefore providing sufficient physicochemical support and giving space for bone growth. This study aims to develop an injectable biomaterial with bone regeneration‐adapted degradability, to reconstruct a biomimetic bone‐like structure that can timely transform into new bone, facilitating functional bone regeneration. To achieve this goal, a hybrid (LP‐CPC@gelatin, LC) hydrogel is synthesized via one‐step incorporation of laponite (LP) and CPC into gelatin hydrogel, and the LC gel degradation rate is controlled by adjusting the LP/CPC ratio to match the bone regeneration rate. Such an LC hydrogel shows good osteoinduction, osteoconduction, and angiogenesis effects, with complete implant‐to‐new bone transformation capacity. This 2D nanoclay‐based bionic hydrogel can induce ectopic bone regeneration and promote ligament graft osseointegration in vivo by inducing functional bone regeneration. Therefore, this study provides an advanced strategy for functional bone regeneration and an injectable biomimetic biomaterial for functional skeletal muscle repair in a minimally invasive therapy.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.BIOMATERIALS.2015.04.044
Abstract: Osteoblast lineage cells are direct effectors of osteogenesis and are, therefore, commonly used to evaluate the in vitro osteogenic capacity of bone substitute materials. This method has served its purposes when testing novel bone biomaterials however, inconsistent results between in vitro and in vivo studies suggest the mechanisms that govern a material's capacity to mediate osteogenesis are not well understood. The emerging field of osteoimmunology and immunomodulation has informed a paradigm shift in our view of bone biomaterials-from one of an inert to an osteoimmunomodulatory material-highlighting the importance of immune cells in materials-mediated osteogenesis. Neglecting the importance of the immune response during this process is a major shortcoming of the current evaluation protocol. In this study we evaluated a potential angiogenic bone substitute material cobalt incorporated with β-tricalcium phosphate (CCP), comparing the traditional "one cell type" approach with a "multiple cell types" approach to assess osteogenesis, the latter including the use of immune cells. We found that CCP extract by itself was sufficient to enhance osteogenic differentiation of bone marrow stem cells (BMSCs), whereas this effect was cancelled out when macrophages were involved. In response to CCP, the macrophage phenotype switched to the M1 extreme, releasing pro-inflammatory cytokines and bone catabolic factors. When the CCP materials were implanted into a rat femur condyle defect model, there was a significant increase of inflammatory markers and bone destruction, coupled with fibrous encapsulation rather than new bone formation. These findings demonstrated that the inclusion of immune cells (macrophages) in the in vitro assessment matched the in vivo tissue response, and that this method provides a more accurate indication of the essential role of immune cells when assessing materials-stimulated osteogenesis in vitro.
Publisher: Mary Ann Liebert Inc
Date: 10-2017
DOI: 10.1089/TEN.TEA.2016.0501
Abstract: The design paradigm of biomaterials has been changed to ones with favorable immunomodulatory effects, indicating the importance of accurately evaluating the immunomodulatory properties of biomaterials. Among all the immune cells macrophages receive most attention, due to their plasticity and multiple roles in the materials and host interactions, and thereby become model immune cells for the evaluation of immunomodulatory properties of biomaterials in many studies. Lipopolysaccharides (LPS), a polysaccharide in the outer membrane of Gram-negative bacteria, elicit strong immune responses, which was often applied to activate macrophages, resulting in a proinflammatory M1 phenotype, and the release of proinflammatory cytokines, including tumor necrosis factor alpha (TNFα), interleukin (IL)-1, and IL-6. However, there is no consensus on how to apply macrophages and LPS to detect the immunomodulatory properties of biomaterials. The lack of scientific consideration of this issue has led to some inaccurate and insufficient conclusions on the immunomodulatory properties of biomaterials, and inconsistences between different research groups. In this study, we carried out a systemic study to investigate the stimulatory effects of LPS with different times, doses, and conditions on the activation of macrophages. An experimental pathway was proposed accordingly for the activation of macrophages using LPS for assessing the immunomodulatory property of biomaterials.
Publisher: Wiley
Date: 04-05-2023
DOI: 10.1002/BTM2.10528
Abstract: Periodontitis is an infection‐induced inflammation, evidenced by an increase in inflammatory macrophage infiltration. Recent research has highlighted the role of plasma‐activated medium (PAM) as a regulator of the innate immune system, where macrophages are the main effector cells. This study therefore aims to investigate the immunomodulatory effects of PAM on macrophages and its potential applications for periodontitis management. PAM was generated using an argon jet and applied to culture macrophages. Proinflammatory macrophage markers were significantly reduced after PAM stimulation, and this was correlated with the activation of autophagy via the Akt signaling pathway. Further investigations on the proregenerative effects of PAM‐treated macrophages on periodontal ligament cells (PDLCs) revealed a significant increase in the expression of osteogeneis/cementogenesis‐associated markers as well as mineralization nodule formation. Our findings suggest that PAM is an excellent candidate for periodontal therapeutic applications.
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.JOEN.2008.06.014
Abstract: Dental pulp cells (DPCs) are capable of differentiating into odontoblasts that secrete reparative dentin after pulp injury. The molecular mechanisms governing reparative dentinogenesis are yet to be fully understood. Here we investigated the differential protein profile of human DPCs undergoing odontogenic induction for 7 days. Using two-dimensional differential gel electrophoresis coupled with matrix-assisted laser adsorption ionization time of flight mass spectrometry, 23 protein spots related to the early odontogenic differentiation were identified. These proteins included cytoskeleton proteins, nuclear proteins, cell membrane-bound molecules, proteins involved in matrix synthesis, and metabolic enzymes. The expression of four identified proteins, which were heteronuclear ribonuclear proteins C, annexin VI, collagen type VI, and matrilin-2, was confirmed by Western blot and real-time real-time polymerase chain reaction analyses. This study generated a proteome reference map during odontoblast-like differentiation of human DPCs, which will be valuable to better understand the underlying molecular mechanisms in odontoblast-like differentiation.
Publisher: Springer Science and Business Media LLC
Date: 24-08-2016
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.ACTBIO.2014.03.035
Abstract: Polymer biomaterials have been widely used for bone replacement/regeneration because of their unique mechanical properties and workability. Their inherent low bioactivity makes them lack osseointegration with host bone tissue. For this reason, bioactive inorganic particles have been always incorporated into the matrix of polymers to improve their bioactivity. However, mixing inorganic particles with polymers always results in inhomogeneity of particle distribution in polymer matrix with limited bioactivity. This study sets out to apply the pulsed laser deposition (PLD) technique to prepare uniform akermanite (Ca2MgSi2O7, AKT) glass nanocoatings on the surface of two polymers (non-degradable polysulfone (PSU) and degradable polylactic acid (PDLLA)) in order to improve their surface osteogenic and angiogenic activity. The results show that a uniform nanolayer composed of amorphous AKT particles (∼30 nm) of thickness 130 nm forms on the surface of both PSU and PDLLA films with the PLD technique. The prepared AKT-PSU and AKT-PDLLA films significantly improved the surface roughness, hydrophilicity, hardness and apatite mineralization, compared with pure PSU and PDLLA, respectively. The prepared AKT nanocoatings distinctively enhance the alkaline phosphate (ALP) activity and bone-related gene expression (ALP, OCN, OPN and Col I) of bone-forming cells on both PSU and PDLLA films. Furthermore, AKT nanocoatings on two polymers improve the attachment, proliferation, VEGF secretion and expression of proangiogenic factors and their receptors of human umbilical vein endothelial cells (HUVEC). The results suggest that PLD-prepared bioceramic nanocoatings are very useful for enhancing the physicochemical, osteogenic and angiogenic properties of both degradable and non-degradable polymers for application in bone replacement/regeneration.
Publisher: Elsevier BV
Date: 09-2017
Publisher: MDPI AG
Date: 05-11-2021
DOI: 10.3390/NANO11112977
Abstract: Dental implants are used broadly in dental clinics as the most natural-looking restoration option for replacing missing or highly diseased teeth. However, dental implant failure is a crucial issue for diabetic patients in need of dentition restoration, particularly when a lack of osseointegration and immunoregulatory incompetency occur during the healing phase, resulting in infection and fibrous encapsulation. Bio-inspired or biomimetic materials, which can mimic the characteristics of natural elements, are being investigated for use in the implant industry. This review discusses different biomimetic dental implants in terms of structural changes that enable antibacterial properties, drug delivery, immunomodulation, and osseointegration. We subsequently summarize the modification of dental implants for diabetes patients utilizing carbon nanomaterials, which have been recently found to improve the characteristics of biomimetic dental implants, including through antibacterial and anti-inflammatory capabilities, and by offering drug delivery properties that are essential for the success of dental implants.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.COMPBIOMED.2012.07.006
Abstract: The finite element (FE) analysis is an effective method to study the strength and predict the fracture risk of endodontically-treated teeth. This paper presents a rapid method developed to generate a comprehensive tooth FE model using data retrieved from micro-computed tomography (μCT). With this method, the inhomogeneity of material properties of teeth was included into the model without iding the tooth model into different regions. The material properties of the tooth were assumed to be related to the mineral density. The fracture risk at different tooth portions was assessed for root canal treatments. The micro-CT images of a tooth were processed by a Matlab software programme and the CT numbers were retrieved. The tooth contours were obtained with thresholding segmentation using Amira. The inner and outer surfaces of the tooth were imported into Solidworks and a three-dimensional (3D) tooth model was constructed. An assembly of the tooth model with the periodontal ligament (PDL) layer and surrounding bone was imported into ABAQUS. The material properties of the tooth were calculated from the retrieved CT numbers via ABAQUS user's subroutines. Three root canal geometries (original and two enlargements) were investigated. The proposed method in this study can generate detailed 3D finite element models of a tooth with different root canal enlargements and filling materials, and would be very useful for the assessment of the fracture risk at different tooth portions after root canal treatments.
Publisher: American Chemical Society (ACS)
Date: 09-12-2009
DOI: 10.1021/BM800937G
Abstract: Amphiphilic triblock copolymers of methoxy-poly(ethylene glycol)-poly(L-lactide)-poly(L-lysine) (MPEG-b-PLLA-b-PLL) (Mn=8540-22 240) were synthesized through the ring-opening polymerization of Nepsilon-(Z)-lysine-N-carboxyanhydrides (N(epsilon)-(Z)-Lys-NCA) using MPEG-b-PLLA-NH2 as a macroinitiator. The triblock copolymers and diblock precursors were characterized by 1H NMR, ATR-FTIR, and GPC. The chain lengths of each block could be controlled by varying the feed ratios of the monomers. The surface properties of films of PLLA modified by blending with the triblock copolymers were investigated by XPS and AFM and demonstrated an enrichment of PLL blocks on the surface of the PLLA film. No cytotoxicity was detected on a range of modified PLLA films arising from the incorporation of the triblock copolymers. The triblock copolymers MPEG-b-PLLA-b-PLL showed better surface properties in promoting osteoblast adhesion and proliferation compared with pure PLLA and PLLA modified with MPEG-b-PLLA diblock copolymers. This study demonstrated that the triblock copolymers containing free amino groups, which self-segregate on the surface of biodegradable polyesters, have potential for applications in cell delivery and tissue engineering.
Publisher: Wiley
Date: 13-02-2012
DOI: 10.1111/J.1600-0722.2012.00942.X
Abstract: Stimulated human whole saliva (WS) was used to study the dynamics of papain hydrolysis at defined pH, ionic strength, and temperature with the view of reducing an acquired pellicle. A quartz crystal microbalance with dissipation (QCM-D) was used to monitor the changes in frequency caused by enzyme hydrolysis of WS films, and the hydrolytic parameters were calculated using an empirical model. The morphological and conformational changes of the salivary films before and after enzymatic hydrolysis were characterized by atomic force microscopy (AFM) imaging and grazing-angle Fourier transform infrared (GA-FTIR ) spectra, respectively. The characteristics of papain hydrolysis of WS films were pH-, ionic strength-, and temperature-dependent. The WS films were partially removed by the action of papain, resulting in thinner and smoother surfaces. The infrared data suggested that hydrolysis-induced deformation did not occur on the remnants of salivary films. The processes of papain hydrolysis of WS films can be controlled by properly regulating pH, ionic strength, and temperature.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2013
DOI: 10.1038/NCOMMS2905
Abstract: Small interfering RNA silences specific genes by interfering with mRNA translation, and acts to modulate or inhibit specific biological pathways a therapy that holds great promise in the cure of many diseases. However, the naked small interfering RNA is susceptible to degradation by plasma and tissue nucleases and due to its negative charge unable to cross the cell membrane. Here we report a new polymer carrier designed to mimic the influenza virus escape mechanism from the endosome, followed by a timed release of the small interfering RNA in the cytosol through a self-catalyzed polymer degradation process. Our polymer changes to a negatively charged and non-toxic polymer after the release of small interfering RNA, presenting potential for multiple repeat doses and long-term treatment of diseases.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6NR06421C
Abstract: The osteoimmune environment plays indispensable roles in bone regeneration because the early immune environment that exists during the regenerative process promotes the recruitment and differentiation of osteoblastic lineage cells. The response of immune cells growing on nanotopographic surfaces and the microenvironment they generate should be considered when evaluating nanotopography-mediated osteogenesis, which are topics that are generally neglected in the field. In this study, we investigated the modulatory effects of nanoporous anodic alumina with different sized pores on macrophage responses and their subsequent effects on the osteogenic differentiation of bone marrow stromal cells (BMSCs). The nanopore structure and the pore size were found to be important adhesive cues for macrophages, which affected their spreading and cell shape, subsequently regulated the expression and activation of autophagy pathway components (LC3A/B, Beclin-1, Atg3, Atg7, and P62) and modulated the inflammatory response, osteoclastic activities, and release of osteogenic factors. Subsequently, the osteogenic pathways (Wnt and BMP) of BMSCs were found to be regulated by different nanopore-induced inflammatory environments, which affected the osteogenic differentiation outcomes. This study is the first to emphasize the effects of immune cells on nanotopography-mediated osteogenesis, which could lead to a new strategy for the development of advanced nanobiomaterials for tissue engineering, nanomedicine and immunotherapeutic applications.
Publisher: Wiley
Date: 21-03-2011
DOI: 10.1111/J.1600-0765.2011.01356.X
Abstract: The molecular mechanism linking atherosclerosis formation and periodontal pathogens is not clear, although a positive correlation between periodontal infections and cardiovascular diseases has been reported. The aim of this study was to determine whether stimulation with Porphyromonas gingivalis lipopolysaccharide (LPS) affected the expression of atherosclerosis-related genes, during and after the formation of foam cells. Macrophages from human THP-1 monocytes were treated with oxidized low-density lipoprotein (oxLDL) to induce the formation of foam cells. P. gingivalis LPS was added to cultures of either oxLDL-induced macrophages or foam cells. The expression of atherosclerosis-related genes was assayed by quantitative real-time PCR, and the production of granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein-1, interleukin (IL)-1β, IL-10 and IL-12 proteins was determined using ELISA. Nuclear translocation of nuclear factor-kappaB (NF-κB) P(65) was detected by immunocytochemistry, and western blotting was used to evaluate inhibitory kappa B-α (IκΒ-α) degradation to confirm activation of the NF-κB pathway. P. gingivalis LPS stimulated atherosclerosis-related gene expression in foam cells and increased the oxLDL-induced expression of chemokines, adhesion molecules, growth factors, apoptotic genes and nuclear receptors in macrophages. Transcription of the proinflammatory cytokines IL1β and IL12 was elevated in response to LPS in both macrophages and foam cells, whereas transcription of the anti-inflammatory cytokine, IL10, was not affected. Increased activation of the NF-κB pathway was also observed in macrophages costimulated with LPS + oxLDL. P. gingivalis LPS appears to be an important factor in the development of atherosclerosis by stimulation of atherosclerosis-related gene expression in both macrophages and foam cells via activation of the NF-κB pathway.
Publisher: Elsevier
Date: 2019
Publisher: Elsevier BV
Date: 11-2021
Publisher: Mary Ann Liebert Inc
Date: 06-2013
Abstract: Recent studies demonstrated that the endogenous expression level of Sox2, Oct-4, and c-Myc is correlated with the pluripotency and successful induction of induced pluripotent stem cells. Periodontal ligament cells (PDLCs) have a multilineage differentiation capability and ability to maintain the undifferentiated stage, which makes PDLCs a suitable cell source for tissue repair and regeneration. To elucidate the effect of an in vitro culture condition on the stemness potential of PDLCs, we explored the cell growth, proliferation, cell cycle, and the expression of Sox2, Oct-4, and c-Myc in PDLCs from the passage 1 to 7 with or without the addition of recombinant human bone morphogenetic protein-4 (rhBMP4). Our results revealed that BMP-4 promoted cell growth and proliferation, arrested PDLCs in the S phase of cell cycle, and upregulated the propidium iodinate value. It was revealed that without the addition of rhBMP4, the expression of Sox2, Oct-4, and c-Myc in PDLCs only maintained the nucleus location until passage 3, and then lost the nucleus location subsequently. The mRNA expression in PDLCs further confirmed that the level of Sox2 and Oct-4 peaked at passage 3 and then decreased afterward, whereas c-Myc maintained consistently the upregulation along the passages. After the treatment with rhBMP4, the expression of Sox2, Oct-4, and c-Myc in PDLCs maintained the nucleus location even at passage 7, and the mRNA expression of Sox2 and Oct-4 significantly upregulated at the passages 5 and 7. These results demonstrated that addition of rhBMP-4 in the culture medium could improve the current culture condition for PDLCs to maintain in an undifferentiated stage.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2014
DOI: 10.1007/S00198-014-2735-0
Abstract: Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis. While much investigation is focused on preventing disease progression, here we fabricate strontium-containing scaffolds and show that they enhance bone defect healing in the femurs of rats induced by ovariectomy. Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis due to its ability to prevent bone loss in osteoporotic patients. Although much emphasis has been placed on using pharmacological agents for the prevention of disease, much less attention has been placed on the construction of biomaterials following osteoporotic-related fracture. The aim of the present study was to incorporate bioactive strontium (Sr) trace element into mesoporous bioactive glass (MBG) scaffolds and to investigate their in vivo efficacy for bone defect healing in the femurs of rats induced by ovariectomy. In total, 30 animals were ided into five groups as follows: (1) empty defect (control), (2) empty defects with estrogen replacement therapy, (3) defects filled with MBG scaffolds alone, (4) defects filled with MBG + estrogen replacement therapy, and (5) defects filled with strontium-incorporated mesopore-bioglass (Sr-MBG) scaffolds. The two groups demonstrating the highest levels of new bone formation were the defects treated with MBG + estrogen replacement therapy and the defects receiving Sr-MBG scaffolds as assessed by μ-CT and histological analysis. Furthermore, Sr scaffolds had a reduced number of tartrate-resistant acid phosphatase-positive cells when compared to other modalities. The results from the present study demonstrate that the local release of Sr from bone scaffolds may improve fracture repair. Future large animal models are necessary to investigate the future relationship of Sr incorporation into biomaterials.
Publisher: Elsevier BV
Date: 03-2008
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.JOEN.2010.12.012
Abstract: Dental pulp cells (DPCs) have shown promising potential in dental tissue repair and regeneration. However, during in vitro culture, these cells undergo replicative senescence and result in significant alteration in cell proliferation and differentiation. Recently, the transcription factors of Oct-4, Sox2, c-Myc, and Klf4 have been reported to play a regulatory role in the stem cell self-renewal process, namely cell reprogramming. Therefore, it is interesting to know whether the replicative senescence during the culture of dental pulp cells is related to the diminishing of the expression of these transcription factors. In this study, we investigated the expression of the reprogramming markers Oct-4, Sox2, and c-Myc in the in vitro explant cultured dental pulp tissues and explant cultured dental pulp cells (DPCs) at various passages by immunofluorescence staining and real-time polymerase chain reaction analysis. Our results demonstrated that Oct-4, Sox2, and c-Myc translocated from nucleus in the first 2 passages to cytoplasm after the third passage in explant cultured DPCs. The mRNA expression of Oct-4, Sox2, and c-Myc elevated significantly over the first 2 passages, peaked at second passage (P < .05), and then decreased along the number of passages afterwards (P < .05). For the first time we demonstrated that the expression of reprogramming markers Oct-4, Sox2, and c-Myc was detectable in the early passaged DPCs, and the sequential loss of these markers in the nucleus during DPC cultures might be related to the cell fate of dental pulp derived cells during the long-term in vitro cultivation under current culture conditions.
Publisher: Wiley
Date: 10-07-2016
DOI: 10.1111/CID.12257
Abstract: Osteocytes, the most abundant cells in bone, have multiple functions, including acting as mechanosensors and regulating mineralization. It is clear that osteocytes influence bone remodeling by controlling the differentiation and activity of osteoblasts and osteoclasts. Determining the relationship between titanium implants and osteocytes may therefore benefit our understanding of the process of osseointegration. The aim of this study was to visualize the ultrastructural relationship between osteocytes and the titanium implant surface following osseointegration in vivo. Titanium implants were placed in the maxillary molar regions of eight female Sprague Dawley rats, 3 months old. The animals were sacrificed 8 weeks after implantation, and undecalcified tissue sections were prepared. Resin-cast s les were subsequently acid-etched with 37% phosphoric acid prior to examination using scanning electron microscopy. Compared with mature bone, where the osteocytes were arranged in an ordered fashion, the osteocytes appeared less organized in the newly formed bone around the titanium implant. Further, a layer of mineralization with few organic components was observed on the implant surface. This study shows for the first time that osteocytes and their dendrites are directly connected with the implant surface. This study shows the direct anchorage of osteocytes via dendritic processes to a titanium implant surface in vivo. This suggests an important regulatory role for osteocytes and their lacunar-canalicular network in maintaining long-term osseointegration.
Publisher: Wiley
Date: 02-2001
DOI: 10.1034/J.1600-0765.2001.00608.X
Abstract: Both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2 (PAI-2) are important proteolysis factors present in inflamed human periodontal tissues. The aim of the present study was to investigate the effect of lipopolysaccharide (LPS) on the synthesis of t-PA and PAI-2 by human gingival fibroblasts (HGF). LPS from different periodontal pathogens including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum were extracted by the hot phenol water method. The levels of t-PA and PAI-2 secreted into the cell culture media were measured by enzyme-linked immunosorbent assays (ELISA). The mRNA for t-PA and PAI-2 were measured by RT-PCR. The results showed t-PA synthesis was increased in response to all types of LPS studied and PAI-2 level was increased by LPS from A. actinomycetemcomitans and F. nucleatum, but not P. gingivalis. When comparing the effects of LPS from non-periodontal bacteria (Escherichia coli and Salmonella enteritidis) with the LPS from periodontal pathogens, we found that the ratio of t-PA to PAI-2 was greater following exposure of the cells to LPS from periodontal pathogens. The highest ratio of t-PA to PAI-2 was found in those cells exposed to LPS from P. gingivalis. These results indicate that LPS derived from periodontal pathogens may cause unbalanced regulation of plasminogen activator and plasminogen activator inhibitor by HGF and such an effect may, in part, contribute to the destruction of periodontal connective tissue through dysregulated pericellular proteolysis.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.BIOMATERIALS.2017.11.020
Abstract: Bone tumor is one of major challenging issues clinically. After surgical intervention, a few bone tumor cells still remain around bone defects and then proliferate over days. Fabrication of specific biomaterials with dual functions of bone tumor therapy and bone regeneration is of great significance. In order to achieve this aim, we managed to prepare bioactive glass (BG) scaffolds functionalized by the CuFeSe
Publisher: Springer Science and Business Media LLC
Date: 21-10-2016
DOI: 10.1038/SREP35645
Abstract: The quality of hematomas are crucial for successful early bone defect healing, as the structure of fibrin clots can significantly influence the infiltration of cells, necessary for bone regeneration, from adjacent tissues into the fibrin network. This study investigated if there were structural differences between hematomas from normal and delayed healing bone defects and whether such differences were linked to changes in the expression of IL-1β. Using a bone defect model in rats, we found that the hematomas in the delayed healing model had thinner fibers and denser clot structures. Moreover, IL-1β protein levels were significantly higher in the delayed healing hematomas. The effects of IL-1β on the structural properties of human whole blood clots were evaluated by thrombelastograph (TEG), scanning electronic microscopy (SEM), compressive study, and thrombolytic assays. S-nitrosoglutathione (GSNO) was applied to modulate de novo hematoma structure and the impact on bone healing was evaluated in the delayed healing model. We found that GSNO produced more porous hematomas with thicker fibers and resulted in significantly enhanced bone healing. This study demonstrated that IL-1β and GSNO had opposing effects on clot architecture, the structure of which plays a pivotal role in early bone healing.
Publisher: Elsevier
Date: 2021
Publisher: Wiley
Date: 15-06-2015
DOI: 10.1002/JBMR.2445
Abstract: Canonical Wnt signaling is important in tooth development but it is unclear whether it can induce cementogenesis and promote the regeneration of periodontal tissues lost because of disease. Therefore, the aim of this study is to investigate the influence of canonical Wnt signaling enhancers on human periodontal ligament cell (hPDLCs) cementogenic differentiation in vitro and cementum repair in a rat periodontal defect model. Canonical Wnt signaling was induced by (1) local injection of lithium chloride (2) local injection of sclerostin antibody and (3) local injection of a lentiviral construct overexpressing β-catenin. The results showed that the local activation of canonical Wnt signaling resulted in significant new cellular cementum deposition and the formation of well-organized periodontal ligament fibers, which was absent in the control group. In vitro experiments using hPDLCs showed that the Wnt signaling pathway activators significantly increased mineralization, alkaline phosphatase (ALP) activity, and gene and protein expression of the bone and cementum markers osteocalcin (OCN), osteopontin (OPN), cementum protein 1 (CEMP1), and cementum attachment protein (CAP). Our results show that the activation of the canonical Wnt signaling pathway can induce in vivo cementum regeneration and in vitro cementogenic differentiation of hPDLCs.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB01747F
Abstract: When a bone substitute biomaterial is implanted into the body, the material's surface comes into contact with circulating blood, which results in the formation of a peri-implant hematoma or blood clot.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.ACTBIO.2019.01.051
Abstract: Titanium (Ti) based tissue engineering scaffolds can be used to repair damaged bone. However, successful orthopedic applications of these scaffolds rely on their ability to mimic the mechanical properties of trabecular bone. Selective laser melting (SLM) was used to manufacture scaffolds of a new β-Ti35Zr28Nb alloy for biomedical applications. Porosity values of the scaffolds were 83% for the FCCZ structure (face centered cubic unit cell with longitudinal struts) and 50% for the FBCCZ structure (face and body centered cubic unit cell with longitudinal struts). The scaffolds had an elastic modulus of ∼1 GPa and a plateau strength of 8-58 MPa, which fall within the values of trabecular bone (0.2-5 GPa for elastic modulus and 4-70 MPa for compressive strength). The SLM-manufactured β-Ti35Zr28Nb alloy showed good corrosion properties. MTS assay revealed that both the FCCZ and FBCCZ scaffolds had a cell viability similar to the control. SEM observation indicated that the osteoblast-like cells adhered, spread and grew healthily on the surface of both scaffolds after culture for 7, 14 and 28 d, demonstrating good biocompatibility. Overall, the SLM-manufactured Ti35Zr28Nb scaffolds possess promising potential as hard-tissue implant materials due to their appropriate mechanical properties, good corrosion behavior and biocompatibility. STATEMENT OF SIGNIFICANCE: Novel β Ti35Zr28Nb alloy scaffolds with FCCZ and FBCCZ structures were successfully fabricated by selective laser melting (SLM) for biomedical applications. The scaffolds showed values of elastic modulus of ∼1 GPa and plateau strength of 8-58 MPa, which fall within the ranges of the mechanical properties of trabecular bone. The SLM-manufactured β Ti35Zr28Nb alloy showed good corrosion properties. Both SLM-manufactured FCCZ and FBCCZ scaffolds exhibited good biocompatibility, with osteoblast-like cells attaching, growing, and spreading in a healthy way on their surfaces after culturing for different periods up to 28 d.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2020
Publisher: Mary Ann Liebert Inc
Date: 09-2009
Publisher: Elsevier BV
Date: 06-2023
Publisher: OMICS Publishing Group
Date: 2015
Publisher: Wiley
Date: 18-02-2016
DOI: 10.1111/CLR.12571
Abstract: Published information regarding the use of rat jawbones for dental implant osseointegration research is limited and often inconsistent. This study assessed the suitability and feasibility of placing dental implants into the rat maxilla and to establish parameters to be used for dental implant research using this model. Forty-two customized titanium implants (2 × 3 mm) were placed bilaterally in the maxillary first molar area of 21 Sprague-Dawley rats. Every animal received two implants. The animals were subsequently sacrificed at days 3, 7, 14, 28 and 56 post-surgery. Resin-embedded sections of the implant and surrounding maxilla were prepared for histological and histomorphometric analyses. The mesial root of the first molar in the rat maxilla was the optimal site to place the implant. Although the most apical 2-3 threads of the implant penetrated into the sinus cavity, 2 mm of the remaining implant was embedded in the bone. New bone formation at day 7 around the implant increased further at day 14, as measured by the percentage of bone-to-implant contact (%BIC) and new bone area (%BA) in the implant thread chambers (55.1 ± 8.9% and 63.7 ± 7.7%, respectively). There was a further significant increase between day 14 and 28 (P < 0.05), however, no significant differences were found between day 28 and 56 in either %BIC or %BA. The mesial root socket of the first molar in the rat maxilla is a useful model for dental implant research. Osseointegration following implant placement as measured by BIC plateaued after 28 days. The recommended implant dimensions are 1.5 mm in diameter and 2 mm in length.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Wiley
Date: 10-11-2017
DOI: 10.1002/JCB.25758
Abstract: Osteoarthritis (OA) is a progressive, age-related disease characterized by the degradation of the cartilage, abnormal bone remodeling, and joint pain eventually leading to disability. The occurrence of clinically diagnosed OA and the incidence of disability show geographic variations, which suggests that lifestyle and factors such as diet play a vital role in the formation and progression of OA. Obesity is associated with a state of low-grade inflammation and increased plasma concentrations of fatty acids such as the saturated fatty acids (SFA). Importantly, obesity is a major risk factor for the development of OA in both weight-bearing and non-weight-bearing joints. Further, obese in iduals bear the full brunt of OA which poses a huge health, social and economic problem, and hence it is essential to increase our understanding of OA and obesity to improve patient care and decrease disease progression. Hence, the current state of knowledge on the relationship between obesity and OA is reviewed, especially the influence of different diets. In particular, we emphasize the role and mechanisms of SFA to cause or worsen OA. J. Cell. Biochem. 118: 453-463, 2017. © 2016 Wiley Periodicals, Inc.
Publisher: Elsevier BV
Date: 03-2007
DOI: 10.1016/J.BONE.2006.10.021
Abstract: Osteoporosis is a multi-factorial, age-related disease with a complex etiology and mode of regulation involving a large numbers of genes. To better understand the possible relationships among genes, we fingerprinted genes in a rat model induced by ovariectomy to determine differences among osteoporotic, non-osteoporotic, aged and juvenile rats. We applied genome wide cDNA microarray technology to analyze genes expressed in bone marrow mesenchymal stromal cells (BMSC) and compared non-osteoporotic adult vs. osteoporotic, non-osteoporotic adult vs. aged, and non-osteoporotic adult vs. juvenile. Rigorous statistical analysis of functional annotation (EASE program) identified over-represented biological and molecular functions with significant group wide changes (p< or =0.05). Some of the expressed genes were further confirmed by quantitative RT-PCR (reverse transcription-polymerase chain reaction). Differences in gene expression were observed by identifying transcripts selected by t-test that were consistently changed by a minimum of two-fold. There were 195 transcripts that showed an increased expression and 109 transcripts that showed decreased expression relative to the osteoporotic condition. Of these, 75% transcripts were unknown gene products or ESTs (expressed sequence tag). A number of genes found in the aged and juvenile groups were not present in the osteoporotic rats. Functional clustering of the genes using the EASE bioinformatics program revealed that transcripts in osteoporosis were associated with signal transduction, lipid metabolism, protein metabolism, ionic and protein transport, neuropeptide and G protein signaling pathways. Although some of the genes have previously been shown to play a key role in osteoporosis, several genes were uniquely identified in this study and likely play a role in developing aged related osteoporosis that could have compelling implications in the development of new diagnostic strategies and therapeutics for osteoporosis. These data suggest that osteoporosis is associated with changes of multiple novel gene expression and that numerous pathways could play important roles in osteoporosis pathogenesis.
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.BIOMATERIALS.2013.11.014
Abstract: Immune reactions play important roles in determining the in vivo fate of bone substitute materials, either in new bone formation or inflammatory fibrous tissue encapsulation. The paradigm for the development of bone substitute materials has been shifted from inert to immunomodulatory materials, emphasizing the importance of immune cells in the material evaluation. Macrophages, the major effector cells in the immune reaction to implants, are indispensable for osteogenesis and their heterogeneity and plasticity render macrophages a primer target for immune system modulation. However, there are very few reports about the effects of macrophages on biomaterial-regulated osteogenesis. In this study, we used β-tricalcium phosphate (β-TCP) as a model biomaterial to investigate the role of macrophages on the material stimulated osteogenesis. The macrophage phenotype switched to M2 extreme in response to β-TCP extracts, which was related to the activation of calcium-sensing receptor (CaSR) pathway. Bone morphogenetic protein 2 (BMP2) was also significantly upregulated by the β-TCP stimulation, indicating that macrophage may participate in the β-TCP stimulated osteogenesis. Interestingly, when macrophage-conditioned β-TCP extracts were applied to bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of BMSCs was significantly enhanced, indicating the important role of macrophages in biomaterial-induced osteogenesis. These findings provided valuable insights into the mechanism of material-stimulated osteogenesis, and a strategy to optimize the evaluation system for the in vitro osteogenesis capacity of bone substitute materials.
Publisher: SAGE Publications
Date: 04-05-2011
Abstract: Collagen fibrillation within articular cartilage (AC) plays a key role in joint osteoarthritis (OA) progression and, therefore, studying collagen synthesis changes could be an indicator for use in the assessment of OA. Various staining techniques have been developed and used to determine the collagen network transformation under microscopy. However, because collagen and proteoglycan coexist and have the same index of refraction, conventional methods for specific visualization of collagen tissue is difficult. This study aimed to develop an advanced staining technique to distinguish collagen from proteoglycan and to determine its evolution in relation to OA progression using optical and laser scanning confocal microscopy (LSCM). A number of AC s les were obtained from sheep joints, including both healthy and abnormal joints with OA grades 1 to 3. The s les were stained using two different trichrome methods and immunohistochemistry (IHC) to stain both colourimetrically and with fluorescence. Using optical microscopy and LSCM, the present authors demonstrated that the IHC technique stains collagens only, allowing the collagen network to be separated and directly investigated. Fluorescently-stained IHC s les were also subjected to LSCM to obtain three-dimensional images of the collagen fibres. Changes in the collagen fibres were then correlated with the grade of OA in tissue. This study is the first to successfully utilize the IHC staining technique in conjunction with laser scanning confocal microscopy. This is a valuable tool for assessing changes to articular cartilage in OA.
Publisher: Bentham Science Publishers Ltd.
Date: 09-2021
DOI: 10.2174/0929867327666201118161232
Abstract: Osteoarthritis (OA) is a degenerative disease of cartilage and bones, which results in severely compromised quality of life in the aged population. However, currently, no ideal treatment strategies have been developed to prevent OA progression. Cell therapies, such as chondrocyte and MSC transplantation, have been extensively tested and evaluated in clinical trials. Yet, to day, the clinical efficacy of articular injection of stem cells in OA has not been convincingly demonstrated. Recent studies have indicated that exosomes, one type of Extracellular Vesicles (EVs) play an important regulatory role in the pathogenesis of OA, suggesting the prospective therapeutic application of exosomes in OA treatment. In this review, we systematically summarized the paracrine effects of exosomes derived from MSCs and chondrocytes on cartilage regeneration, the use of exosomes as a delivery vehicle for OA treatment, the effectiveness of such treatments in OA animal models, and the future perspective of exosome-mediated drug delivery as a cell- free therapy of OA.
Publisher: Hindawi Limited
Date: 07-08-2019
DOI: 10.1002/TERM.2947
Abstract: Bone marrow-derived mesenchymal stem/stromal cells (BMSCs) can differentiate into bone-forming osteoblasts, playing a crucial role in bone regeneration. Exosomes are naturally cell-secreted nanovesicles and are lately regraded as an emerging mediator of cellular communication in physiological and pathological conditions. The present study aimed at investigating the complex cellular communications, especially those among the differentiating BMSCs, immune cells (e.g., macrophages), and newly recruited BMSCs via exosome-mediated pathways. Exosomes were first isolated from osteogenically differentiating BMSCs at various stages (Day 0, Day 3, Day 7, and Day 14, respectively). The cellular uptake of isolated exosomes was examined in macrophages and human BMSCs (hBMSCs). The exosomes collected at various osteogenic differentiation stages (0d-exo, 3d-exo, 7d-exo, and 14d-exo) had no effect on the viability of hBMSCs. The uptake of exosomes (0d-exo, 3d-exo, and 7d-exo) significantly decreased proinflammatory-gene expression and the level of an M1 phenotypic marker. Our results then revealed that 3d-exo, 7d-exo, and 14d-exo led to a remarkable increase in mesenchymal stem/stromal cell migration. In addition, 0d-exo significantly promoted the expression of early osteogenic markers, such as alkaline phosphatase and bone morphogenetic protein 2, indicating a pro-osteogenic role of hBMSC-derived exosomes. Collectively, these results suggest that exosomes derived from differentiating mesenchymal stem/stromal cells play a unique osteoimmunomodulatory role in the regulation of bone dynamics.
Publisher: Mary Ann Liebert Inc
Date: 04-2018
Publisher: Wiley
Date: 22-04-2014
Publisher: Elsevier BV
Date: 12-2023
Publisher: Elsevier BV
Date: 10-2021
Publisher: Springer International Publishing
Date: 2015
Publisher: Springer International Publishing
Date: 2015
Publisher: Wiley
Date: 29-04-2023
Abstract: Tendon‐to‐bone interface has a hierarchical structure and gradient component that are conducive to distributing the stresses to achieve movement. Conventional biomaterials lack the capacity to induce synchronous repair of multiple tissues, resulting in the failure of the interface repair. Biomimetic strategies have attracted enormous attention in the field of complex structure regeneration because they can meet the different physiological requirements of multiple tissues. Herein, a biomimetic ink mimicking tendon/bone tissues is developed by combining tendon/bone‐related cells and Mo‐containing silicate (MS) bioceramics. Subsequently, biomimetic multicellular scaffolds are fabricated to achieve the simulation of the hierarchical structure and cellular composition of tendon‐to‐bone interfaces by the spatial distribution of the biomimetic inks via 3D bioprinting, which is of great significance for inducing the regeneration of complex structures in the interface region. In addition, attributed to the desirable ionic microenvironment created by MS bioceramics, the biomimetic scaffolds possess the dual function of inducing tendon/bone‐related cells tenogenic and osteogenic differentiation in vitro, and promote the integrated regeneration of tendon‐to‐bone interfaces in vivo. The study offers a feasible strategy to construct biomimetic multicellular scaffolds with bifunction for inducing multi‐lineage tissue regeneration, especially for regenerating soft‐to‐hard tissue interfaces.
Publisher: American Chemical Society (ACS)
Date: 21-02-2017
DOI: 10.1021/ACS.CHEMREV.6B00654
Abstract: Although the biological functions of cell and tissue can be regulated by biochemical factors (e.g., growth factors, hormones), the biophysical effects of materials on the regulation of biological activity are receiving more attention. In this Review, we systematically summarize the recent progress on how biomaterials with controllable properties (e.g., compositional/degradable dynamics, mechanical properties, 2D topography, and 3D geometry) can regulate cell behaviors (e.g., cell adhesion, spreading, proliferation, cell alignment, and the differentiation or self-maintenance of stem cells) and tissue/organ functions. How the biophysical features of materials influence tissue/organ regeneration have been elucidated. Current challenges and a perspective on the development of novel materials that can modulate specific biological functions are discussed. The interdependent relationship between biomaterials and biology leads us to propose the concept of "materiobiology", which is a scientific discipline that studies the biological effects of the properties of biomaterials on biological functions at cell, tissue, organ, and the whole organism levels. This Review highlights that it is more important to develop ECM-mimicking biomaterials having a self-regenerative capacity to stimulate tissue regeneration, instead of attempting to recreate the complexity of living tissues or tissue constructs ex vivo. The principles of materiobiology may benefit the development of novel biomaterials providing combinative bioactive cues to activate the migration of stem cells from endogenous reservoirs (i.e., cell niches), stimulate robust and scalable self-healing mechanisms, and unlock the body's innate powers of regeneration.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.BIOMATERIALS.2018.02.010
Abstract: A multifaceted coating for hard tissue implants, with favorable osteogenesis, angiogenesis, and osteoimmunomodulation abilities, would be of great value since it could improve osseointegration and alleviate prosthesis loosening. However, to date there are few coatings that fully satisfy these criteria. Herein we describe a microporous TiO
Publisher: Springer Science and Business Media LLC
Date: 21-11-2020
DOI: 10.1007/S40820-020-00540-Z
Abstract: The immune response of a biomaterial determines its osteoinductive effect. Although the mechanisms by which some immune cells promote regeneration have been revealed, the biomaterial-induced immune response is a dynamic process involving multiple cells. Currently, it is challenging to accurately regulate the innate and adaptive immune responses to promote osteoinduction in biomaterials. Herein, we investigated the roles of macrophages and dendritic cells (DCs) during the osteoinduction of biphasic calcium phosphate (BCP) scaffolds. We found that osteoinductive BCP directed M2 macrophage polarization and inhibited DC maturation, resulting in low T cell response and efficient osteogenesis. Accordingly, a dual-targeting nano-in-micro scaffold (BCP loaded with gold nanocage, BCP-GNC) was designed to regulate the immune responses of macrophages and DCs. Through a dual-wavelength photosensitive switch, BCP-GNC releases interleukin-4 in the early stage of osteoinduction to target M2 macrophages and then releases dexamethasone in the later stage to target immature DCs, creating a desirable inflammatory environment for osteogenesis. This study demonstrates that biomaterials developed to have specific regulatory capacities for immune cells can be used to control the early inflammatory responses of implanted materials and induce osteogenesis.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Elsevier BV
Date: 05-2017
Publisher: Wiley
Date: 26-01-2021
DOI: 10.1111/JDI.13477
Abstract: Periodontal disease, a chronic inflammation induced by bacteria, is closely linked with diabetes mellitus. Many complications associated with diabetes are related to epigenetic changes. However, the exact epigenetic changes whereby diabetes affects periodontal disease remain largely unknown. Thus, we sought to investigate the role of diabetes‐dependent epigenetic changes of gingival tissue in the susceptibility to periodontal disease. We studied the effect of streptozotocin‐induced diabetes in minipigs on gingival morphological and epigenetic tissue changes. Accordingly, we randomly ided six minipigs into two groups: streptozotocin‐induced diabetes group, n = 3 and non‐diabetes healthy control group, n = 3. After 85 days, all animals were killed, and gingival tissue was collected for histology, deoxyribonucleic acid methylation analysis and immunohistochemistry. A diabetes mellitus model was successfully created, as evidenced by significantly increased blood glucose levels, reduction of pancreatic insulin‐producing β‐cells and histopathological changes in the kidneys. The gingival tissues in the diabetes group presented acanthosis of both gingival squamous epithelium and sulcular/junctional epithelium, and a significant reduction in the number and length of rete pegs. Deoxyribonucleic acid methylation analysis showed a total of 1,163 affected genes, of which 599 and 564 were significantly hypermethylated and hypomethylated, respectively. Immunohistochemistry staining showed that the hypomethylated genes – tumor necrosis factor‐α and interleukin‐6 – were positively expressed under the junctional epithelium area in the diabetes group. Diabetes mellitus induces morphological and epigenetic changes in periodontal tissue, which might contribute to the increased susceptibility of periodontal diseases in patients with diabetes.
Publisher: Elsevier BV
Date: 03-2021
Publisher: MDPI AG
Date: 09-03-2021
DOI: 10.3390/NANO11030674
Abstract: Implant surfaces with a nanoscaled pattern can dominate the blood coagulation process resulting in a defined clot structure and its degradation behavior, which in turn influence cellular response and the early phase of osseointegration. Long non-coding (Lnc) RNAs are known to regulate many biological processes in the skeletal system however, the link between the LncRNA derived from the cells within the clot and osseointegration has not been investigated to date. Hence, the sequence analysis of LncRNAs expressed within the clot formed on titania nanotube arrays (TNAs) with distinct nano-scaled diameters (TNA 15 of 15 nm, TNA 60 of 60 nm, TNA 120 of 120 nm) on titanium surfaces was profiled for the first time. LncRNA LOC103346307, LOC103352121, LOC108175175, LOC103348180, LOC108176660, and LOC108176465 were identified as the pivotal players in the early formed clot on the nano-scaled surfaces. Further bioinformatic prediction results were used to generate co-expression networks of LncRNAs and mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that distinct nano-scaled surfaces could regulate the biological functions of target mRNAs in the clot. LOC103346307, LOC108175175, and LOC108176660 upregulated mRNAs related to cell metabolism and Wnt, TGF-beta, and VEGF signaling pathways in TNA 15 compared with P-Ti, TNA 60, and TNA 120, respectively, whereas LOC103352121, LOC103348180, and LOC108176465 downregulated mRNAs related to bone resorption and inflammation through negatively regulating osteoclast differentiation, TNF, and NF-kappa signaling pathways. The results indicated that surface nano-scaled characteristics can significantly influence the clot-derived LncRNAs expression profile, which affects osseointegration through multiple signaling pathways of the targeted mRNAs, thus paving a way for better interpreting the link between the properties of a blood clot formed on the nano-surface and de novo bone formation.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.BIOMATERIALS.2012.09.066
Abstract: It is of great importance to develop multifunctional bioactive scaffolds, which combine angiogenesis capacity, osteostimulation, and antibacterial properties for regenerating lost bone tissues. In order to achieve this aim, we prepared copper (Cu)-containing mesoporous bioactive glass (Cu-MBG) scaffolds with interconnective large pores (several hundred micrometer) and well-ordered mesopore channels (around 5 nm). Both Cu-MBG scaffolds and their ionic extracts could stimulate hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression in human bone marrow stromal cells (hBMSCs). In addition, both Cu-MBG scaffolds and their ionic extracts significantly promoted the osteogenic differentiation of hBMSCs by improving their bone-related gene expression (alkaline phosphatase (ALP), osteopontin (OPN) and osteocalcin (OCN)). Furthermore, Cu-MBG scaffolds could maintain a sustained release of ibuprofen and significantly inhibited the viability of bacteria. This study indicates that the incorporation of Cu(2+) ions into MBG scaffolds significantly enhances hypoxia-like tissue reaction leading to the coupling of angiogenesis and osteogenesis. Cu(2+) ions play an important role to offer the multifunctional properties of MBG scaffold system. This study has demonstrated that it is possible to develop multifunctional scaffolds by combining enhanced angiogenesis potential, osteostimulation, and antibacterial properties for the treatment of large bone defects.
Publisher: Elsevier BV
Date: 2017
Publisher: Springer Science and Business Media LLC
Date: 04-11-2016
DOI: 10.1038/IJOS.2016.33
Publisher: Public Library of Science (PLoS)
Date: 24-02-2016
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.JOEN.2009.07.005
Abstract: During development and regeneration, odontogenesis and osteogenesis are initiated by a cascade of signals driven by several master regulatory genes. In this study, we investigated the differential expression of 84 stem cell-related genes in dental pulp cells (DPCs) and periodontal ligament cells (PDLCs) undergoing odontogenic/osteogenic differentiation. Our results showed that, although there was considerable overlap, certain genes had more differential expression in PDLCs than in DPCs. CCND2, DLL1, and MME were the major upregulated genes in both PDLCs and DPCs, whereas KRT15 was the only gene significantly downregulated in PDLCs and DPCs in both odontogenic and osteogenic differentiation. Interestingly, a large number of regulatory genes in odontogenic and osteogenic differentiation interact or crosstalk via Notch, Wnt, transforming growth factor beta (TGF-beta)/bone morphogenic protein (BMP), and cadherin signaling pathways, such as the regulation of APC, DLL1, CCND2, BMP2, and CDH1. Using a rat dental pulp and periodontal defect model, the expression and distribution of both BMP2 and CDH1 have been verified for their spatial localization in dental pulp and periodontal tissue regeneration. This study has generated an overview of stem cell-related gene expression in DPCs and PDLCs during odontogenic/osteogenic differentiation and revealed that these genes may interact through the Notch, Wnt, TGF-beta/BMP, and cadherin signaling pathways to play a crucial role in determining the fate of dental derived cell and dental tissue regeneration. These findings provided a new insight into the molecular mechanisms of the dental tissue mineralization and regeneration.
Publisher: Wiley
Date: 1998
DOI: 10.1111/J.1600-0765.1998.TB02287.X
Abstract: The relative distribution of urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2) was studied in cultured human gingival fibroblasts, healthy gingival tissues and inflamed gingival tissues by immunohistochemistry. In cultured gingival fibroblasts t-PA, u-PA and PAI-1 were expressed in cytoplasm u-PA and PAI-1 were more intensely stained than t-PA PAI-2 was not detectable in gingival fibroblasts. Following interleukin 1 beta (IL-1 beta) stimulation, the intensity of intracellular staining for t-PA was increased and a number of cells staining strongly for PAI-2 were seen no difference in the intensity of immunostaining level was noted for the expression of u-PA and PAI-1 between IL-1 beta stimulated cells and unstimulated cells. In healthy gingival tissues, u-PA and PAI-1 displayed a wide distribution throughout all the connective tissue and epithelium t-PA localized mainly in the connective tissue while PAI-2 showed little association with the connective tissue but did faintly stain in the epithelial layer. In inflamed gingival tissues, staining for t-PA was significantly increased in the extracellular matrix of the connective tissue, whereas staining for u-PA, PAI-1 and PAI-2 was found to be slightly increased, but no significant difference was noted for staining when compared with the healthy gingival tissues. A granular distribution of t-PA, u-PA, PAI-1 and PAI-2 was noted around areas of inflammatory cell infiltration. These immunohistochemical findings indicate that the plasminogen activator system produced by fibroblasts may be influenced by the presence of the inflammatory mediator IL-1 beta. In addition, the significant increase of t-PA in inflamed connective tissue and the wide expression of these components around inflamed cells may contribute to connective tissue degradation and may relate to the migration and localization of monocytes/macrophages in inflamed tissue.
Publisher: Hindawi Limited
Date: 05-10-2015
DOI: 10.1002/TERM.1619
Abstract: The interaction between host and donor cells is believed to play an important role in osteogenesis. However, it is still unclear how donor osteogenic cells behave and interact with host cells in vivo. The purpose of this study was to track the interactions between transplanted osteogenic cells and host cells during osteogenesis. In vitro migration assay was carried out to investigate the ability of osteogenic differentiated human mesenchymal stem cells (O-hMSCs) to recruit MSCs. At the in vivo level, O-hMSCs were implanted subcutaneously or into skull defects in severe combined immunodeficient (SCID) mice. New bone formation was observed by micro-CT and histological procedures. In situ hybridization (ISH) against human Alu sequences was performed to distinguish donor osteogenic cells from host cells. In vitro migration assay revealed an increased migration potential of MSCs by co-culturing with O-hMSCs. In agreement with the results of in vitro studies, ISH against human Alu sequences showed that host mouse MSCs migrated in large numbers into the transplantation site in response to O-hMSCs. Interestingly, host cells recruited by O-hMSCs were the major cell populations in newly formed bone tissues, indicating that O-hMSCs can trigger and initiate osteogenesis when transplanted in orthotopic sites. The observations from this study demonstrated that in vitro induced O-hMSCs were able to attract host MSCs in vivo and were involved in osteogenesis together with host cells, which may be of importance for bone tissue-engineering applications.
Publisher: Springer Singapore
Date: 2020
Publisher: SAGE Publications
Date: 2009
DOI: 10.4137/BTRI.S3188
Abstract: Two common methods have been used to evaluate the in vitro bioactivity of bioceramics for the application of bone repair. One is to evaluate the ability of apatite formation by soaking ceramics in simulated body fluids (SBF) the other method is to evaluate the effect of ceramics on osteogenic differentiation using cell experiments. Both methods have their own drawbacks in evaluating the in vitro bioactivity of bioceramics. In this commentary paper we review the application of both methods in bioactivity of bioceramics and conclude that (i) SBF method is an efficient method to investigate the in vitro bioactivity of silicate-based bioceramics, (ii) cellular bioactivity of bioceramics should be investigated by evaluating their stimulatory ability using standard bioceramics as controls and (iii) the combination of these two methods to evaluate the in vitro bioactivity of bioceramics can improve the screening efficiency for the selection of bioactive ceramics for bone regeneration.
Publisher: MDPI AG
Date: 21-06-2016
DOI: 10.3390/IJMS17060977
Publisher: Wiley
Date: 26-10-2012
DOI: 10.1111/JACE.12059
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.BIOMATERIALS.2011.11.042
Abstract: Low oxygen pressure (hypoxia) plays an important role in stimulating angiogenesis there are, however, few studies to prepare hypoxia-mimicking tissue engineering scaffolds. Mesoporous bioactive glass (MBG) has been developed as scaffolds with excellent osteogenic properties for bone regeneration. Ionic cobalt (Co) is established as a chemical inducer of hypoxia-inducible factor (HIF)-1α, which induces hypoxia-like response. The aim of this study was to develop hypoxia-mimicking MBG scaffolds by incorporating ionic Co(2+) into MBG scaffolds and investigate if the addition of Co(2+) ions would induce a cellular hypoxic response in such a tissue engineering scaffold system. The composition, microstructure and mesopore properties (specific surface area, nano-pore volume and nano-pore distribution) of Co-containing MBG (Co-MBG) scaffolds were characterized and the cellular effects of Co on the proliferation, differentiation, vascular endothelial growth factor (VEGF) secretion, HIF-1α expression and bone-related gene expression of human bone marrow stromal cells (BMSCs) in MBG scaffolds were systematically investigated. The results showed that low amounts of Co (<5%) incorporated into MBG scaffolds had no significant cytotoxicity and that their incorporation significantly enhanced VEGF protein secretion, HIF-1α expression, and bone-related gene expression in BMSCs, and also that the Co-MBG scaffolds support BMSC attachment and proliferation. The scaffolds maintain a well-ordered mesopore channel structure and high specific surface area and have the capacity to efficiently deliver antibiotics drugs in fact, the sustained released of icillin by Co-MBG scaffolds gives them excellent anti-bacterial properties. Our results indicate that incorporating cobalt ions into MBG scaffolds is a viable option for preparing hypoxia-mimicking tissue engineering scaffolds and significantly enhanced hypoxia function. The hypoxia-mimicking MBG scaffolds have great potential for bone tissue engineering applications by combining enhanced angiogenesis with already existing osteogenic properties.
Publisher: MDPI AG
Date: 18-02-2020
DOI: 10.3390/NU12020509
Abstract: Osteoarthritis (OA) is a degenerative condition of joints, causing pain and swelling, and can be caused or worsened by trauma and obesity. The objectives of this study were to determine whether pain behaviour and progression of OA were increased in rats with trauma-induced OA fed dietary saturated fatty acids (SFA). Male Wistar rats were fed either a corn starch diet (C) or high-carbohydrate high-fat diet (H) with either 20% beef tallow or SFA (lauric (HLA), myristic (HMA), palmitic (HPA) or stearic (HSA) acids) for 16 weeks prior to and 8 weeks after excision of the medial meniscus of right knee joint to initiate OA when pain behaviour, glial activity, progression of knee OA, inflammatory mediators and signs of metabolic syndrome were assessed. Rats fed beef tallow, palmitic or stearic acids showed increased pain symptoms characterised by decreased hind paw/limb withdrawal thresholds and grip strengths and increased spinal astrogliosis and microgliosis compared to rats fed lauric or myristic acids. However, the severity of OA joint damage was unchanged by these dietary manipulations. We conclude that pain symptoms of trauma-induced OA in rats worsen with increased dietary beef tallow or palmitic or stearic acids, but improve with lauric or myristic acids, despite unchanged OA cartilage damage.
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.BONE.2009.10.014
Abstract: Osteoarthritic subchondral bone is characterized by abnormal bone density and enhanced production of bone turnover markers, an indication of osteoblast dysfunction. Several studies have proposed that pathological changes in articular cartilage influence the subchondral bone changes, which are typical of the progression of osteoarthritis however, direct evidence of this has yet to be reported. The aim of the present study was to investigate what effects articular cartilage cells, isolated from normal and osteoarthritic joints, may have on the subchondral bone osteoblast phenotype, and also the potential involvement of the mitogen activated protein kinase (MAPK) signalling pathway during this process. Our results suggest that chondrocytes isolated from a normal joint inhibited osteoblast differentiation, whereas chondrocytes isolated from an osteoarthritic joint enhanced osteoblast differentiation, both via a direct and indirect cell interaction mechanisms. Furthermore, the interaction of subchondral bone osteoblasts with osteoarthritic chondrocyte conditioned media appeared to significantly activate ERK1/2 phosphorylation. On the other hand, conditioned media from normal articular chondrocytes did not affect ERK1/2 phosphorylation. Inhibition of the MAPK-ERK1/2 pathways reversed the phenotype changes of subchondral bone osteoblast, which would otherwise be induced by the conditioned media from osteoarthritic chondrocytes. In conclusion, our findings provide evidence that osteoarthritic chondrocytes affect subchondral bone osteoblast metabolism via an ERK1/2 dependent pathway.
Publisher: Wiley
Date: 09-11-2020
Publisher: Springer Science and Business Media LLC
Date: 06-2010
Publisher: Spandidos Publications
Date: 31-10-2016
Publisher: Elsevier BV
Date: 02-2019
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/546097
Abstract: Periodontitis is an inflammatory disease that causes osteolysis and tooth loss. It is known that the nuclear factor kappa B (NF- κ B) signalling pathway plays a key role in the progression of inflammation and osteoclastogenesis in periodontitis. Parthenolide (PTL), a sesquiterpene lactone extracted from the shoots of Tanacetum parthenium , has been shown to possess anti-inflammatory properties in various diseases. In the study reported herein, we investigated the effects of PTL on the inflammatory and osteoclastogenic response of human periodontal ligament-derived cells (hPDLCs) and revealed the signalling pathways in this process. Our results showed that PTL decreased NF- κ B activation, I- κ B degradation, and ERK activation in hPDLCs. PTL significantly reduced the expression of inflammatory (IL-1 β , IL-6, and TNF- α ) and osteoclastogenic (RANKL, OPG, and M-CSF) genes in LPS-stimulated hPDLCs. In addition, PTL attenuated hPDLC-induced osteoclastogenic differentiation of macrophages (RAW264.7 cells), as well as reducing gene expression of osteoclast-related markers in RAW264.7 cells in an hPDLC-macrophage coculture model. Taken together, these results demonstrate the anti-inflammatory and antiosteoclastogenic activities of PTL in hPDLCs in vitro . These data offer fundamental evidence supporting the potential use of PTL in periodontitis treatment.
Publisher: Elsevier BV
Date: 05-2023
DOI: 10.1016/J.JOCA.2022.11.004
Abstract: Metabolic pathways are a series of chemical reactions by which cells take in nutrient substrates for energy and building blocks needed to maintain critical cellular processes. Details of chondrocyte metabolism and how it rewires during the progression of osteoarthritis (OA) are unknown. This research aims to identify what changes in the energy metabolic state occur in OA cartilage. Patient matched OA and non-OA cartilage specimens were harvested from total knee replacement patients. Cartilage was first collected for metabolomics, proteomics, and transcriptomics analyses to study global alterations in OA metabolism. We then determined the metabolic routes by tracking [U- OA chondrocytes showed increased basal ECAR and more lactate production compared to non-OA chondrocytes. [U- This study represents the first comprehensive comparative analysis of metabolism in OA chondrocytes and lays the groundwork for therapeutic targeting of metabolism in OA.
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.BIOMATERIALS.2015.08.027
Abstract: A number of coating materials have been developed over past two decades seeking to improve the osseointegration of orthopedic metal implants. Despite the many candidate materials trialed, their low rate of translation into clinical applications suggests there is room for improving the current strategies for their development. We therefore propose that the ideal coating material(s) should possess the following three properties: (i) high bonding strength, (ii) release of functional ions, and (iii) favourable osteoimmunomodulatory effects. To test this proposal, we developed clinoenstatite (CLT, MgSiO3), which as a coating material has high bonding strength, cytocompability and immunomodulatory effects that are favourable for in vivo osteogenesis. The bonding strength of CLT coatings was 50.1 ± 3.2 MPa, more than twice that of hydroxyapatite (HA) coatings, at 23.5 ± 3.5 MPa. CLT coatings released Mg and Si ions, and compared to HA coatings, induced an immunomodulation more conducive for osseointegration, demonstrated by downregurelation of pro-inflammatory cytokines, enhancement of osteogenesis, and inhibition of osteoclastogenesis. In vivo studies demonstrated that CLT coatings improved osseointegration with host bone, as shown by the enhanced biomechanical strength and increased de novo bone formation, when compared with HA coatings. These results support the notion that coating materials with the proposed properties can induce an in vivo environment better suited for osseointegration. These properties could, therefore, be fundamental when developing high-performance coating materials.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.BIOMATERIALS.2013.09.074
Abstract: Cell-based therapy is considered a promising approach to achieving predictable periodontal regeneration. In this study, the regenerative potential of cell sheets derived from different parts of the periodontium (gingival connective tissue, alveolar bone and periodontal ligament) were investigated in an athymic rat periodontal defect model. Periodontal ligament (PDLC), alveolar bone (ABC) and gingival margin-derived cells (GMC) were obtained from human donors. The osteogenic potential of the primary cultures was demonstrated in vitro. Cell sheets supported by a calcium phosphate coated melt electrospun polycaprolactone (CaP-PCL) scaffold were transplanted to denuded root surfaces in surgically created periodontal defects, and allowed to heal for 1 and 4 weeks. The CaP-PCL scaffold alone was able to promote alveolar bone formation within the defect after 4 weeks. The addition of ABC and PDLC sheets resulted in significant periodontal attachment formation. The GMC sheets did not promote periodontal regeneration on the root surface and inhibited bone formation within the CaP-PCL scaffold. In conclusion, the combination of either PDLC or ABC sheets with a CaP-PCL scaffold could promote periodontal regeneration, but ABC sheets were not as effective as PDLC sheets in promoting new attachment formation.
Publisher: MDPI AG
Date: 10-02-2023
DOI: 10.3390/NANO13040692
Abstract: Treatment of large bone fractures remains a challenge for orthopedists. Bone regeneration is a complex process that includes skeletal cells such as osteoblasts, osteoclasts, and immune cells to regulate bone formation and resorption. Osteoimmunology, studying this complicated process, has recently been used to develop biomaterials for advanced bone regeneration. Ideally, a biomaterial shall enable a timely switch from early stage inflammatory (to recruit osteogenic progenitor cells) to later-stage anti-inflammatory (to promote differentiation and terminal osteogenic mineralization and model the microstructure of bone tissue) in immune cells, especially the M1-to-M2 phenotype switch in macrophage populations, for bone regeneration. Nanoparticle (NP)-based advanced drug delivery systems can enable the controlled release of therapeutic reagents and the delivery of therapeutics into specific cell types, thereby benefiting bone regeneration through osteoimmunomodulation. In this review, we briefly describe the significance of osteoimmunology in bone regeneration, the advancement of NP-based approaches for bone regeneration, and the application of NPs in macrophage-targeting drug delivery for advanced osteoimmunomodulation.
Publisher: Frontiers Media SA
Date: 23-07-2019
Publisher: Frontiers Media SA
Date: 10-05-2021
DOI: 10.3389/FCELL.2021.659654
Abstract: Osteoarthritis (OA) is a long-term condition that causes joint pain and reduced movement. Notably, the same pathways governing cell growth, death, and differentiation during the growth and development of the body are also common drivers of OA. The osteochondral interface is a vital structure located between hyaline cartilage and subchondral bone. It plays a critical role in maintaining the physical and biological function, conveying joint mechanical stress, maintaining chondral microenvironment, as well as crosstalk and substance exchange through the osteochondral unit. In this review, we summarized the progress in research concerning the area of osteochondral junction, including its pathophysiological changes, molecular interactions, and signaling pathways that are related to the ultrastructure change. Multiple potential treatment options were also discussed in this review. A thorough understanding of these biological changes and molecular mechanisms in the pathologic process will advance our understanding of OA progression, and inform the development of effective therapeutics targeting OA.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.ACTBIO.2012.05.008
Abstract: Topographically and chemically modified titanium implants are recognized to have improved osteogenic properties however, the molecular regulation of this process remains unknown. This study aimed to determine the microRNA profile and the potential regulation of osteogenic differentiation following early exposure of osteoprogenitor cells to sand-blasted, large-grit acid-etched (SLA) and hydrophilic SLA (modSLA) surfaces. Firstly, the osteogenic characteristics of the primary osteoprogenitor cells were confirmed using ALP activity and Alizarin Red S staining. The effect of smooth (SMO), SLA and modSLA surfaces on the TGF-β/BMP (BMP2, BMP6, ACVR1) and non-canonical WNT/Ca(2+) (WNT5A, FZD6) pathways, as well as the integrins ITGB1 and ITGA2, was determined. It was revealed that the modified titanium surfaces could induce the activation of TGF-β/BMP and non-canonical WNT/Ca(2+) signaling genes. The expression pattern of microRNAs (miRNAs) related to cell differentiation was evaluated. Statistical analysis of the differentially regulated miRNAs indicated that 35 and 32 miRNAs were down-regulated on the modSLA and SLA surfaces respectively, when compared with the smooth surface (SMO). Thirty-one miRNAs that were down-regulated were common to both modSLA and SLA. There were 10 miRNAs up-regulated on modSLA and nine on SLA surfaces, amongst which eight were the same as observed on modSLA. TargetScan predictions for the down-regulated miRNAs revealed genes of the TGF-β/BMP and non-canonical Ca(2+) pathways as targets. This study demonstrated that modified titanium implant surfaces induce differential regulation of miRNAs, which potentially regulate the TGF-β/BMP and WNT/Ca(2+) pathways during osteogenic differentiation on modified titanium implant surfaces.
Publisher: Public Library of Science (PLoS)
Date: 31-08-2017
Publisher: Wiley
Date: 30-09-2022
Publisher: Trans Tech Publications, Ltd.
Date: 09-2011
DOI: 10.4028/WWW.SCIENTIFIC.NET/JBBTE.11.81
Abstract: Vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMP-7) are key regulators of angiogenesis and osteogenesis during bone regeneration. The aim of this study was to investigate the possibility of realizing sequential release of the two growth factors using a novel composite scaffold. Poly(lactic-co-glycolic acid) (PLGA)-Akermanite (AK) microspheres were used to make the composite scaffold, which was then loaded with BMP-7, followed by embedding in a gelatin hydrogel matrix loaded with VEGF. The release profiles of the growth factors were studied and selected osteogenic related markers of bone marrow stromal cells (BMSCs) were analysed. It was shown that the composite scaffolds exhibited a fast initial burst release of VEGF within the first 3 days and a sustained slow release of BMP-7 over the full period of 20 days. The in vitro proliferation and differentiation of the BMSCs cultured in the osteogenic medium were enhanced by 1 to 2 times, resulting from the additionally and sequentially release of growth factors from the PLGA-AK/gelatin composite scaffolds.
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/241067
Publisher: Frontiers Media SA
Date: 22-03-2000
Abstract: Obesogenic diets contribute to the pathology of osteoarthritis (OA) by altering systemic and local metabolic inflammation. Yet, it remains unclear how quickly and reproducibly the body responds to weight loss strategies and improve OA. In this study we tested whether switching obese diet to a normal chow diet can mitigate the detrimental effects of inflammatory pathways that contribute to OA pathology. Male C57BL/6 mice were first fed with obesogenic diet (high fat diet) and switched to normal chow diet (obese diet → normal diet) or continued obese diet or normal diet throughout the experiment. A mouse model of OA was induced by surgical destabilization of the medial meniscus (DMM) model into the knee joint. Outcome measures included changes in metabolic factors such as glucose, insulin, lipid, and serum cytokines levels. Inflammation in synovial biopsies was scored and inflammation was determined using FACs sorted macrophages. Cartilage degeneration was monitored using histopathology. Our results indicate, dietary switching (obese diet → normal diet) reduced body weight and restored metabolic parameters and showed less synovial tissue inflammation. Systemic blood concentrations of pro-inflammatory cytokines IL-1α, IL-6, IL-12p40, and IL-17 were decreased, and anti-inflammatory cytokines IL-4 and IL-13 were increased in dietary switch group compared to mice that were fed with obesogenic diet continuously. Although obese diet worsens the cartilage degeneration in DMM OA model, weight loss induced by dietary switch does not promote the histopathological changes of OA during this study period. Collectively, these data demonstrate that switching obesogenic diet to normal improved metabolic syndrome symptoms and can modulate both systemic and synovium inflammation levels.
Publisher: SAGE Publications
Date: 08-2001
DOI: 10.1177/00220345010800081201
Abstract: In dentinogenesis, certain growth factors, matrix proteoglycans, and proteins are directly or indirectly dependent on growth hormone. The hypothesis that growth hormone up-regulates the expression of enzymes, sialoproteins, and other extracellular matrix proteins implicated in the formation and mineralization of tooth and bone matrices was tested by the treatment of Lewis dwarf rats with growth hormone over 5 days. The molar teeth were processed for immunohistochemical demonstration of bone-alkaline phosphatase, bone morphogenetic proteins-2 and -4, osteocalcin, osteopontin, bone sialoprotein, and Ell protein. Odontoblasts responded to growth hormone by more cells expressing bone morphogenetic protein, alkaline phosphatase, osteocalcin, and osteopontin. No changes were found in bone sialoprotein or E11 protein expression. Thus, growth hormone may stimulate odontoblasts to express several growth factors and matrix proteins associated with dentin matrix biosynthesis in mature rat molars.
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/738239
Abstract: Poly( l -lactide) (PLLA), a versatile biodegradable polymer, is one of the most commonly-used materials for tissue engineering applications. To improve cell affinity for PLLA, poly(ethylene glycol) (PEG) was used to develop diblock copolymers. Human bone marrow stromal cells (hBMSCs) were cultured on MPEG- b -PLLA copolymer films to determine the effects of modification on the attachment and proliferation of hBMSC. The mRNA expression of 84 human extracellular matrix (ECM) and adhesion molecules was analyzed using RT-qPCR to understand the underlying mechanisms. It was found that MPEG- b -PLLA copolymer films significantly improved cell adhesion, extension, and proliferation. This was found to be related to the significant upregulation of two adhesion genes, CDH1 and CTNND2, which encode 1-cadherin and delta-2-catenin, respectively, two key components for the cadherin-catenin complex. In summary, MPEG- b -PLLA copolymer surfaces improved initial cell adhesion by stimulation of adhesion molecule gene expression.
Publisher: Wiley
Date: 02-09-2015
DOI: 10.1111/CLR.12672
Abstract: The initial contact of blood with biomaterials and subsequent recruitment of inflammatory and marrow-derived stromal cells are among the first phases of bone regeneration. The aim of this study was to investigate the migratory potential of mesenchymal stem cells by treating rat bone marrow mesenchymal stromal cells (rBMSCs) with the extract of the blood clot formed on implant surfaces. Cell attachment and morphology on the blood clot was observed using scanning electron microscopy. The cell metabolism was reflected by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, and the cell proliferation was assessed by the CyQuant(®) assay based on DNA content. Cytokine profiles in the incubation medium derived from different blood-titanium surface were detected using the rat cytokine antibody array. Scratch wound assay and transwell migration assay were performed to determine the effect of blood-implant conditioned medium on cell migration and movement. No significant difference was found in cell attachment and morphology on the blood clot formed on smooth and rough surfaces. Increased rBMSC proliferation was induced by the blood clot on rough surfaces. Comparison of cytokine secretion showed a significant increase of CINC-2α, IL-2, L-selectin, MCP-1, prolactin AA and VEGF levels in the elution of blood clot formed on rough titanium surfaces, which led to significantly improved mobility and wound healing ability of rBMSCs. Rough titanium surfaces could influence the blood clot formation and properties, which will induce cell recruitment and stimulate wound healing.
Publisher: Elsevier BV
Date: 09-2004
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/890675
Abstract: Introduction . Stem cells are regularly cultured under normoxic conditions. However, the physiological oxygen tension in the stem cell niche is known to be as low as 1-2% oxygen, suggesting that hypoxia has a distinct impact on stem cell maintenance. Periodontal ligament cells (PDLCs) and dental pulp cells (DPCs) are attractive candidates in dental tissue regeneration. It is of great interest to know whether hypoxia plays a role in maintaining the stemness and differentiation capacity of PDLCs and DPCs. Methods . PDLCs and DPCs were cultured either in normoxia (20% O 2 ) or hypoxia (2% O 2 ). Cell viability assays were performed and the expressions of pluripotency markers (Oct-4, Sox2, and c-Myc) were detected by qRT-PCR and western blotting. Mineralization, glycosaminoglycan (GAG) deposition, and lipid droplets formation were assessed by Alizarin red S, Safranin O, and Oil red O staining, respectively. Results . Hypoxia did not show negative effects on the proliferation of PDLCs and DPCs. The pluripotency markers and differentiation potentials of PDLCs and DPCs significantly increased in response to hypoxic environment. Conclusions . Our findings suggest that hypoxia plays an important role in maintaining the stemness and differentiation capacity of PDLCs and DPCs.
Publisher: Wiley
Date: 20-07-2010
DOI: 10.1002/JBM.A.32873
Abstract: Microsphere systems with the ideal properties for bone regeneration need to be bioactive, and at the same time possess the capacity for controlled protein/drug-delivery however, the current crop of microsphere system fails to fulfill these properties. The aim of this study was to develop a novel protein-delivery system of bioactive mesoporous glass (MBG) microspheres by a biomimetic method through controlling the density of apatite on the surface of microspheres, for potential bone tissue regeneration. MBG microspheres were prepared by using the method of alginate cross-linking with Ca(2+) ions. The cellular bioactivity of MBG microspheres was evaluated by investigating the proliferation and attachment of bone marrow stromal cell (BMSC). The loading efficiency (LE) and release kinetics of bovine serum albumin (BSA) on MBG microspheres were investigated after coprecipitating with biomimetic apatite in simulated body fluids (SBF). The results showed that MBG microspheres supported BMSC attachment and the Si-containing ionic products from MBG microspheres stimulated BMSCs proliferation. The density of apatite on MBG microspheres increased with the length of soaking time in SBF. BSA-LE of MBG was significantly enhanced by coprecipitating with apatite. Furthermore, the LE and release kinetics of BSA could be controlled by controlling the density of apatite formed on MBG microspheres. Our results suggest that MBG microspheres are a promising protein-delivery system as a filling material for bone defect healing and regeneration.
Publisher: MDPI AG
Date: 28-09-2021
DOI: 10.3390/PHARMACEUTICS13101572
Abstract: Porous nanomaterials (PNMs) are nanosized materials with specially designed porous structures that have been widely used in the bone tissue engineering field due to the fact of their excellent physical and chemical properties such as high porosity, high specific surface area, and ideal biodegradability. Currently, PNMs are mainly used in the following four aspects: (1) as an excellent cargo to deliver bone regenerative growth factors/drugs (2) as a fluorescent material to trace cell differentiation and bone formation (3) as a raw material to synthesize or modify tissue engineering scaffolds (4) as a bio-active substance to regulate cell behavior. Recent advances in the interaction between nanomaterials and cells have revealed that autophagy, a cellular survival mechanism that regulates intracellular activity by degrading/recycling intracellular metabolites, providing energy/nutrients, clearing protein aggregates, destroying organelles, and destroying intracellular pathogens, is associated with the phagocytosis and clearance of nanomaterials as well as material-induced cell differentiation and stress. Autophagy regulates bone remodeling balance via directly participating in the differentiation of osteoclasts and osteoblasts. Moreover, autophagy can regulate bone regeneration by modulating immune cell response, thereby modulating the osteogenic microenvironment. Therefore, autophagy may serve as an effective target for nanomaterials to facilitate the bone regeneration process. Increasingly, studies have shown that PNMs can modulate autophagy to regulate bone regeneration in recent years. This paper summarizes the current advances on the main application of PNMs in bone regeneration, the critical role of autophagy in bone regeneration, and the mechanism of PNMs regulating bone regeneration by targeting autophagy.
Publisher: Wiley
Date: 08-2000
DOI: 10.1034/J.1600-0765.2000.035004194.X
Abstract: Nitric oxide is known to be an important inflammatory mediator, and is implicated in the pathophysiology of a range of inflammatory disorders. The aim of this study was to determine the localization and distribution of endothelial NOS (NOS-II) in human gingival tissue, and to ascertain if human gingival fibroblasts express NOS-II when stimulated with interferon gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS). The distribution of NOS-II in inflamed and non-inflamed specimens of human gingivae was studied using a monoclonal antibody against nitric oxide synthase II. Cultures of fibroblasts derived from healthy human gingivae were used for the cell culture experiments. The results from immunohistochemical staining of the tissues indicated an upregulation of NOS-II expression in inflamed compared to non-inflamed gingival tissue. Fibroblasts and inflammatory cells within the inflamed connective tissue were positively stained for NOS-II. In addition, basal keratinocytes also stained strongly for NOS-II, in both healthy and inflamed tissue sections. When cultured human gingival fibroblasts were stimulated by INF-gamma and Porphyromonas gingivalis LPS, NOS-II was more strongly expressed than when the cells were exposed to LPS or IFN-gamma alone. These data suggest that, as for other inflammatory diseases, NO plays a role in the pathophysiology of periodontitis.
Publisher: Springer Science and Business Media LLC
Date: 22-12-2011
DOI: 10.1007/S10856-011-4531-0
Abstract: Calcium (Ca) is the main element of most pulp capping materials and plays an essential role in mineralization. Different pulp capping materials can release various concentrations of Ca ions leading to different clinical outcomes. The purpose of this study was to investigate the effects of various concentrations of Ca ions on the growth and osteogenic differentiation of human dental pulp cells (hDPCs). Different concentrations of Ca ions were added to growth culture medium and osteogenic inductive culture medium. A Cell Counting Kit-8 was used to determine the proliferation of hDPCs in growth culture medium. Osteogenic differentiation and mineralization were measured by alkaline phosphatase (ALP) assay, Alizarin red S/von kossa staining, Ca content quantitative assay. The selected osteogenic differentiation markers were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Within the range of 1.8-16.2 mM, increased concentrations of Ca ions had no effect on cell proliferation, but led to changes in osteogenic differentiation. It was noted that enhanced mineralized matrix nodule formation was found in higher Ca ions concentrations however, ALP activity and gene expression were reduced. qRT-PCR results showed a trend towards down-regulated mRNA expression of type I collagen and Runx2 at elevated concentrations of Ca ions, whereas osteopontin and osteocalcin mRNA expression were significantly up-regulated. Ca ions content in the culture media can significantly influence the osteogenic properties of hDPCs, indicating the importance of optimizing Ca ions release from dental pulp capping materials in order to achieve desirable clinical outcomes.
Publisher: American Chemical Society (ACS)
Date: 14-12-2020
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1016/J.ARCHORALBIO.2005.04.006
Abstract: Emdogain (EMD) is an enamel matrix derivative extracted from developing porcine teeth with demonstrated periodontal regenerative potential. EMD has been shown to influence a number of properties of periodontal ligament cells including proliferation, cell attachment and matrix synthesis. To date, the effect of EMD on the epithelial cell rests of Malassez (ERM) is unknown. In this study, periodontal ligament fibroblasts, ERM, alveolar bone cells and gingival fibroblasts were obtained from porcine periodontal ligament, alveolar bone and gingiva. This study investigated, in vitro, the effect of EMD at three concentrations on proliferation, cell attachment and expression of mRNA for two mineralised tissue-related proteins (osteopontin and bone sialoprotein). As for other periodontal cells, the ERM proliferative response was enhanced by EMD. Attachment assays revealed a highly significant increase for ERM and gingival fibroblasts after EMD treatment at all concentrations. This study has also shown that EMD stimulated expression of osteopontin mRNA by ERM and alveolar bone cells. The results from this study provide evidence that EMD enhanced cellular events related with proliferation, attachment and osteopontin mRNA expression by porcine periodontal cells, in a manner consistent with its role in periodontal regenerative therapy.
Publisher: Informa UK Limited
Date: 12-01-2017
Publisher: Hindawi Limited
Date: 22-03-2018
DOI: 10.1002/TERM.2327
Abstract: Cell-cell interaction is believed to play a critical role in the cell-based therapy for bone regeneration. However, the mechanisms involved in the interaction between donor cells and host cells during the bone healing process are still not clear. This study investigated the potential effect of vascular endothelial growth factor A (VEGFA) produced by osteogenically differentiated mesenchymal stem cells (O-MSCs) on the recruitment and regulation of undifferentiated MSCs and macrophages during osteogenesis. Factors secreted from MSCs during osteogenic differentiation were monitored by cytokine arrays. Indirect coculture models were applied to study the effect of VEGFA derived from O-MSCs on the motility, cell morphology and CXCL12/CXCR4 expression in MSCs as well as the regulation of local immune response. A mouse skull defect model was used to unveil the cell recruitment, macrophage activity and new bone formation following O-MSCs transplantation. It was found that VEGFA secretion increased dramatically during the osteogenic differentiation of MSCs. The secreted VEGFA by O-MSCs stimulated the expression of CXCL12/CXCR4, resulting in the recruitment of MSCs and macrophages to the bone defects. It was noted that O-MSCs could regulate the local inflammation by modulating the expression of proinflammatory cytokines in macrophages and neutralizing VEGFA produced by O-MSCs resulted in significant decrease of cell recruitment, cytokine secretion and new bone formation. This study demonstrates that VEGFA secreted by O-MSCs plays a pivotal role in the cell recruitment and regulation of local immune response during osteogenesis. Copyright © 2016 John Wiley & Sons, Ltd.
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/03008200701458749
Abstract: In view of the controversy of the clinical use of hyperbaric oxygen (HBO) treatment to stimulate fracture healing and bone regeneration, we have analyzed the effects of daily exposure to HBO on the proliferation and differentiation of human osteoblasts in vitro. HBO stimulated proliferation when osteoblasts were cultured in 10% fetal calf serum (FCS), whereas an inhibitory effect of HBO was observed when cultures were supplemented with 2% FCS. On the other hand, HBO enhanced biomineralization with an increase in bone nodule formation, calcium deposition, and alkaline phosphatase activity, whereas no cytotoxic effect was detected using a lactate dehydrogenase activity assay. The data suggest that the exposure of osteoblasts to HBO enhances differentiation toward the osteogenic phenotype, providing cellular evidence of the potential application of HBO in fracture healing and bone regeneration.
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.ACTBIO.2011.03.009
Abstract: New generation biomaterials for bone regeneration should be highly bioactive, resorbable and mechanically strong. Mesoporous bioactive glass (MBG), a novel bioactive material, has been used to study bone regeneration due to its excellent bioactivity, degradation and drug delivery ability, however, the construction of three-dimensional (3-D) MBG scaffolds (as for other bioactive inorganic scaffolds) for bone regeneration remains a significant challenge due to their inherent brittleness and low strength. In this brief communication we report a new facile method to prepare hierarchical and multifunctional MBG scaffolds with a controllable pore architecture, excellent mechanical strength and mineralization ability for application in bone regeneration by a modified 3-D printing technique using polyvinylalcohol (PVA) as a binder. The method provides a new way to solve commonly existing issues for inorganic scaffold materials, for ex le, uncontrollable pore architectures, low strength, high brittleness and the requirement for a second sintering at high temperature. The 3-D printed MBG scaffolds obtained possess a high mechanical strength about 200 times that of traditional polyurethane foam templated MBG scaffolds. They have a highly controllable pore architecture, excellent apatite mineralization ability and sustained drug delivery properties. Our study indicates that 3-D printed MBG scaffolds may be an excellent candidate for bone regeneration.
Publisher: SAGE Publications
Date: 21-04-2023
DOI: 10.1177/19476035231169940
Abstract: Chronic inflammation plays an important role in the osteoarthritis (OA) pathology but how this influence OA disease progression is unclear. Leukotriene B4 (LTB 4 ) is a potent proinflammatory lipid mediator generated from arachidonic acid through the sequential activities of 5-lipoxygenase, 5-lipoxygenase–activating protein, Leukotriene A 4 hydrolase (LTA 4 H) and its downstream product LTB 4 . The aim of this study is to investigate the involvement and the potential therapeutic target of the LTB 4 pathway in OA disease progression. Both clinical human cartilage s les ( n = 7) and mice experimental OA models ( n = 6) were used. The levels of LTA 4 H and leukotriene B4 receptor 1 were first examined using immunostaining in human OA/non-OA cartilage and mice experimental OA models. We also determined whether the LTA 4 H pathway was associated with cartilage degeneration and synovitis inflammation in OA mice models and human articular chondrocytes. We found that both LTA 4 H and LTB 4 receptor (BLT1) were highly expressed in human and mice OA cartilage. Inhibition of LTA 4 H suppressed cartilage degeneration and synovitis in OA mice model. Furthermore, inhibition of LTA 4 H promoted cartilage regeneration by upregulating chondrogenic genes expression such as aggrecan ( ACAN), collagen 2A1 ( COL2A1), and SRY-Box transcription factor 9 ( SOX9). Our results indicate that the LTA 4 H pathway is a crucial regulator of OA pathogenesis and suggest that LTA 4 H could be a therapeutic target in combat OA.
Publisher: Wiley
Date: 18-07-2018
DOI: 10.1111/JMI.12731
Abstract: Ion beam induced heat damage in soft materials and biological s les is not yet well understood in Focused Ion Beam systems (FIBs). The work presented here discusses the physics behind the ion beam - s le interactions and the effects which lead to increases in s le temperature and potential heat damage. A model by which heat damage can be estimated and which allows parameters to be determined that reduce revent heat damage was derived from Fourier's law of heat transfer and compared to finite element simulations, numerical modelling results and experiments. The results suggests that ion beam induced heat damage can be prevented/minimised by reducing the ion beam current (local dose rate), decreasing the beam overlap (reduced local ion dose) and by introducing a blur (increased surface cross-section area, reduced local dose) while sputtering, patterning or imaging soft material and nonresin-embedded biological s les using FIBs. FIB/SEMs, which combine a scanning electron microscope with a focused ion beam in a single device, have found increasing interest biological research. The device allows to cut s les at precisely selected areas and reveal sub surface information as well as preparing transmission electron microscope s les from bulk materials. Preparing biological s les has proven to be challenging due to the induced heat damage. This work explores the physics behind the s le cutting and proposes a model and a method, based on physical principles which allows the user to estimate the induced heat during the cutting process and to select cutting parameters which avoid heat damage in the s le.
Publisher: IOP Publishing
Date: 09-12-2021
Abstract: Inflammation is a critical process in disease pathogenesis and the restoration of tissue structure and function, for ex le, in joints such as the knee and temporomandibular. Within the innate immunity process, the body’s first defense response in joints when physical and chemical barriers are breached is the synovial macrophages, the main innate immune effector cells, which are responsible for triggering the initial inflammatory reaction. Macrophage is broadly ided into three phenotypes of resting M0, pro-inflammatory M1-like (referred to below as M1), and anti-inflammatory M2-like (referred to below as M2). The synovial macrophage M1-to-M2 transition can affect the chondrogenic differentiation of mesenchymal stem cells (MSCs) in joints. On the other hand, MSCs can also influence the transition between M1 and M2. Failure of the chondrogenic differentiation of MSCs can result in persistent cartilage destruction leading to osteoarthritis. However, excessive chondrogenic differentiation of MSCs may cause distorted cartilage formation in the synovium, which is evidenced in the case of synovial chondromatosis. This review summarizes the role of macrophage polarization in the process of both cartilage destruction and regeneration, and postulates that the transition of macrophage phenotype in an inflammatory joint environment may play a key role in determining the fate of joint cartilage.
Publisher: CRC Press
Date: 22-03-2013
DOI: 10.1201/B13926-3
Publisher: CRC Press
Date: 22-03-2013
DOI: 10.1201/B13926-2
Publisher: Frontiers Media SA
Date: 2016
Publisher: Mary Ann Liebert Inc
Date: 04-2008
Abstract: Osteophytes are a distinct feature of osteoarthritis (OA). Their formation may be related to pluripotential cells in the periosteum responding to stimulus during OA. This study aimed to isolate stem cells from osteophyte tissues and to characterize their phenotype, proliferation, and differentiation potential, as well as their immunomodulatory properties. Osteophyte-derived cells were isolated from osteophyte tissue s les collected during knee replacement surgery. These cells were characterized by the expression of cell-surface antigens, differentiation potential into mesenchymal lineages, growth kinetics, and modulation of alloimmune responses. Multipotential stem cells were identified from all osteophyte s les, namely osteophyte-derived mesenchymal stem cells (oMSCs). The surface antigen expression of oMSCs was consistent with that of MSCs they lacked the hematopoietic and common leukocyte markers (CD34, CD45) while expressing those related to adhesion (CD29, CD166, CD44) and stem cells (CD90, CD105, CD73). The proliferation capacity of oMSCs in culture was superior to that of bone marrow-derived MSCs (bMSCs), and these cells readily differentiated into tissues of the mesenchymal lineages. oMSCs also demonstrated the ability to suppress allogeneic T cell proliferation, which was associated with the expression of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Our results showed that osteophyte-derived cells had similar properties to MSCs in the expression of antigen phenotype, differential potential, and suppression of alloimmune response. Furthermore, when compared to bMSCs, oMSCs maintained a higher proliferative capacity, which may offer new insights of the tissue formation and potentially an alternative source for therapeutic stem cell-based tissue regeneration.
Publisher: Public Library of Science (PLoS)
Date: 16-08-2013
Publisher: Springer Science and Business Media LLC
Date: 06-05-2019
DOI: 10.1007/S11926-019-0827-8
Abstract: Osteoarthritis (OA) is a multifactorial and progressive disease affecting whole synovial joint. The extract pathogenic mechanisms and diagnostic biomarkers of OA remain unclear. In this article, we review the studies related to metabolomics of OA, discuss the biomarkers as a tool for early OA diagnosis. Furthermore, we examine the major studies on the application of metabolomics methodology in the complex context of OA and create a bridge from findings in basic science to their clinical utility. Recently, the tissue metabolomics signature permits a view into transitional phases between the healthy and OA joint. Both nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry-based metabolomics approaches have been used to interrogate the metabolic alterations that may indicate the complex progression of OA. Specifically, studies on alterations pertaining to lipids, glucose, and amino acid metabolism have aided in the understanding of the complex pathogenesis of OA. The discovery of identified metabolites could be important for diagnosis and staging of OA, as well as for the assessment of efficacy of new drugs.
Publisher: Informa UK Limited
Date: 08-03-2023
Publisher: Wiley
Date: 08-2017
Abstract: Osteoporosis is associated with widespread periodontitis and impaired periodontal healing. However, there is a lack of information about the outcomes of regenerative approaches under the influence of osteoporosis. This study investigates the effect of leptin (LEP) overexpression on the regenerative potential of bone marrow stromal cells (BMSCs) in an osteoporotic rat periodontal fenestration defect model. Rat BMSCs were transfected with adenoviruses harboring the human (h)LEP gene. Cell proliferation and osteogenic differentiation were evaluated. A β-tricalcium phosphate scaffold seeded with transfected cells was implanted into nude mice to investigate ectopic osteogenesis and into an osteoporotic rat defect to study periodontal regeneration. Regenerated periodontal and bone-like tissues were analyzed by histologic methods. hLEP overexpression induced osteogenic differentiation of BMSCs as evidenced by the upregulation of osteogenesis-related genes such as Runt-related transcription factor 2, alkaline phosphatase (ALP), and collagen Type I, as well as increased ALP activity and enhanced mineralization. Mice implanted with hLEP-BMSC-containing scaffolds showed more extensive formation of bone-like tissue than those in other groups. Periodontal defects were also filled to a greater degree when treated with hLEP-BMSCs and contained cementum and a well-organized periodontal ligament after 10 and 28 days. hLEP overexpression in BMSCs can stimulate periodontal regeneration in osteoporotic conditions and might be a promising strategy for periodontal regeneration in patients with osteoporosis.
Publisher: Elsevier BV
Date: 06-2022
Publisher: Wiley
Date: 04-2000
DOI: 10.1111/J.1708-8208.2000.TB00113.X
Abstract: Demineralized freeze-dried bone allografts (DFDBAs) have been proposed as a useful adjunct in periodontal therapy to induce periodontal regeneration through the induction of new bone formation. The presence of bone morphogenetic proteins (BMPs) within the demineralized matrix has been proposed as a possible mechanism through which DFDBA may exert its biologic effect. However, in recent years, the predictability of results using DFDBA has been variable and has led to its use being questioned. One reason for the variability in tissue response may be attributed to differences in the processing of DFDBA, which may lead to loss of activity of any bioactive substances within the DFDBA matrix. Therefore, the purpose of this investigation was to determine whether there are detectable levels of bone morphogenetic proteins in commercial DFDBA preparations. A single preparation of DFDBA was obtained from three commercial sources. Each preparation was studied in triplicate. Proteins within the DFDBA s les were first extracted with 4M guanidinium HCI for seven days at 40 degrees celsius and the residue was further extracted with 4M guanidinium HCL/EDTA for seven days at 40 degrees celsius. Two anti-human BMP-2 and -4 antibodies were used for the detection of the presence of BMP's in the extracts. Neither BMP-2 nor BMP-4 was detected in any of the extracts. When recombinant human BMP-2 and -4 were added throughout the extraction process of DFDBA extraction, not only were intact proteins detected but smaller molecular weight fragments were also noted in the extract. These results indicate that all of the DFDBA s les tested had no detectable amounts of BMP-2 and -4. In addition, an unknown substance present in the DFDBA may be responsible for degradation of whatever BMPs might be present.
Publisher: Trans Tech Publications, Ltd.
Date: 09-2010
DOI: 10.4028/WWW.SCIENTIFIC.NET/JBBTE.6.1
Abstract: Polymer microspheres loaded with bioactive particles, biomolecules, proteins, and/or growth factors play important roles in tissue engineering, drug delivery, and cell therapy. The conventional double emulsion method and a new method of electrospraying into liquid nitrogen were used to prepare bovine serum albumin (BAS)-loaded poly(lactic-co-glycolic acid) (PLGA) porous microspheres. The particle size, the surface morphology and the internal porous structure of the microspheres were observed using scanning electron microscopy (SEM). The loading efficiency, the encapsulation efficiency, and the release profile of the BSA-loaded PLGA microspheres were measured and studied. It was shown that the microspheres from double emulsion had smaller particle sizes (3-50 m), a less porous structure, a poor loading efficiency (5.2 %), and a poor encapsulation efficiency (43.5%). However, the microspheres from the electrospraying into liquid nitrogen had larger particle sizes (400-600 m), a highly porous structure, a high loading efficiency (12.2%), and a high encapsulation efficiency (93.8%). Thus the combination of electrospraying with freezing in liquid nitrogen and subsequent freeze drying represented a suitable way to produce polymer microspheres for effective loading and sustained release of proteins.
Publisher: Hindawi Limited
Date: 2017
DOI: 10.1155/2017/2931054
Publisher: Springer Science and Business Media LLC
Date: 10-05-2016
DOI: 10.1007/S00109-016-1425-0
Abstract: Osteoarthritis (OA) is a chronic, incurable and destructive joint disease that is characterized by chondrocyte hypertrophy and cartilage degradation. Angiogenesis, mediated by the action of vascular endothelial growth factor (VEGF), is known to be a contributing factor in the pathogenesis of OA. In this study, we use a lentivirus-based approach to investigate whether VEGF knockdown would be beneficial to chondrogenesis and could prevent or slow down OA progression. We first profiled cytokines in human OA cartilage using cytokine antibody arrays. This revealed that as many as 21 angiogenesis-related cytokines were significantly upregulated in severe OA cartilage compared to mild OA s les. Next, we infected chondrocytes with VEGF small hairpin RNA (shRNA) lentivirus (LV-VEGF shRNA) and treated these cells with tumour necrosis factor alpha (TNF-α) to induce hypertrophy. The results showed that inhibition of VEGF not only enhanced chondrogenic differentiation, but also protected chondrocytes from TNF-α-induced hypertrophy. We also found that knockdown of VEGF suppressed TNF-α-induced phosphorylation of ERK1/2 in chondrocytes. Furthermore, using a surgically induced OA rat model, we showed that VEGF inhibition delayed OA progression in animals given intra-articular injection of LV-VEGF shRNA. In conclusion, in this study, we have shown that VEGF knockdown can enhance chondrogenesis and prevent OA progression, thus providing evidence that inhibition of VEGF may be a potential therapeutic approach for OA patients. Numerous pro-angiogenic factors are upregulated in severe OA cartilage. Inhibition of VEGF by shRNA protects chondrocytes from TNF-α-induced hypertrophy. Knockdown of VEGF suppresses TNF-α-induced phosphorylation of ERK1/2 in chondrocytes. VEGF inhibition delays OA progression in rat model in vivo. Inhibition of VEGF may be a potential therapeutic approach for OA patients.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.ACTBIO.2010.02.030
Abstract: The pore architecture of scaffolds is known to play a critical role in tissue engineering as it provides the vital framework for seeded cells to organize into a functioning tissue. In this report we have investigated the effects of different concentrations of silk fibroin protein on three-dimensional (3D) scaffold pore microstructure. Four pore size ranges of silk fibroin scaffolds were made by the freeze drying technique, with the pore sizes ranging from 50 to 300 microm. The pore sizes of the scaffolds decreased as the concentration of fibroin protein increased. Human bone marrow mesenchymal stromal cells (BMSC) transfected with the BMP7 gene were cultured in these scaffolds. A cell viability colorimetric assay, alkaline phosphatase assay and reverse transcription-polymerase chain reaction were performed to analyze the effect of pore size on cell growth, the secretion of extracellular matrix (ECM) and osteogenic differentiation. Cell migration in 3D scaffolds was confirmed by confocal microscopy. Calvarial defects in SCID mice were used to determine the bone forming ability of the silk fibroin scaffolds incorporating BMSC expressing BMP7. The results showed that BMSC expressing BMP7 preferred a pore size between 100 and 300 microm in silk fibroin protein fabricated scaffolds, with better cell proliferation and ECM production. Furthermore, in vivo transplantation of the silk fibroin scaffolds combined with BMSC expressing BMP7 induced new bone formation. This study has shown that an optimized pore architecture of silk fibroin scaffolds can modulate the bioactivity of BMP7-transfected BMSC in bone formation.
Publisher: Mary Ann Liebert Inc
Date: 06-2023
Publisher: Springer Singapore
Date: 24-09-2017
Publisher: Wiley
Date: 11-03-2010
DOI: 10.1002/JBM.B.31621
Abstract: Alginate microspheres are considered a promising material as a drug carrier in bone repair because of excellent biocompatibility, but their main disadvantage is low drug entrapment efficiency and noncontrollable release. The aim of this study was to investigate the effect of incorporating mesoporous bioglass (MBG), nonmesoporous bioglass (BG), or hydroxyapatite (HAp) into alginate microspheres on their drug-loading and release properties. X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and atomic emission spectroscopy (AES) were used to analyze the composition, structure, and dissolution of bioactive inorganic materials and their microspheres. Dexamethasone (DEX)-loading and release ability of four microspheres were tested in phosphate buffered saline with varying pH. Results showed that the drug-loading capacity was enhanced with the incorporation of bioactive inorganic materials into alginate microspheres. The MBG/alginate microspheres had the highest drug loading ability. DEX release from alginate microspheres correlated to the dissolution of MBG, BG, and HAp in PBS, and that the pH was an efficient factor in controlling the DEX release a high pH resulted in greater DEX release, whereas a low pH delayed DEX release. In addition, MBG/alginate, BG/alginate, and HAp/alginate microspheres had varying apatite-formation and dissolution abilities, which indicate that the composites would behave differently with respect to bioactivity. The study suggests that microspheres made of a composite of bioactive inorganic materials and alginate have a bioactivity and degradation profile which greatly improves their drug delivery capacity, thus enhancing their potential applications as bioactive filler materials for bone tissue regeneration.
Publisher: Springer Singapore
Date: 24-09-2017
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8BM00701B
Abstract: The immunomodulatory property of biomaterials is vital in determining the in vivo fate of implants and tissue regeneration.
Publisher: Wiley
Date: 15-10-2023
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.IJOM.2012.06.002
Abstract: This article reviews the literature on the outcome of flapless surgery for dental implants in the posterior maxilla. The literature search was carried out in using the keywords: flapless, dental implants and maxilla. A hand search and Medline search were carried out on studies published between 1971 and 2011. The authors included research involving a minimum of 15 dental implants with a follow-up period of 1 year, an outcome measurement of implant survival, but excluded studies involving multiple simultaneous interventions, and studies with missing data. The Cochrane approach for cohort studies and Oxford Centre for Evidence-Based Medicine were applied. Of the 56 published papers selected, 14 papers on the flapless technique showed high overall implant survival rates. The prospective studies yielded 97.01% (95% CI: 90.72-99.0) while retrospective studies or case series illustrated 95.08% (95% CI: 91.0-97.93) survival. The average of intraoperative complications was 6.55% using the flapless procedure. The limited data obtained showed that flapless surgery in posterior maxilla areas could be a viable and predictable treatment method for implant placement. Flapless surgery tends to be more applicable in this area of the mouth. Further long-term clinical controlled studies are needed.
Publisher: Springer Science and Business Media LLC
Date: 05-2018
DOI: 10.1038/S41598-018-25186-1
Abstract: Knee injury often triggers post-traumatic osteoarthritis (PTOA) that affects articular cartilage (AC), subchondral bone, meniscus and the synovial membrane. The available treatments for PTOA are largely ineffective due to late diagnosis past the “treatment window”. This study aimed to develop a detailed understanding of the time line of the progression of PTOA in murine models through longitudinal observation of the femorotibial joint from the onset of the disease to the advanced stage. Quantitative magnetic resonance microimaging (µMRI) and histology were used to evaluate PTOA-associated changes in the knee joints of rats subjected to knee meniscectomy. Systematic longitudinal changes in the articular cartilage thickness, cartilage T 2 and the T 2 of epiphysis within medial condyles of the tibia were all found to be associated with the development of PTOA in the animals. The following pathogenesis cascade was found to precede advanced PTOA: meniscal injury → AC swelling → subchondral bone remodelling → proteoglycan depletion → free water influx → cartilage erosion. Importantly, the imaging protocol used was entirely MRI-based. This protocol is potentially suitable for whole-knee longitudinal, non-invasive assessment of the development of OA. The results of this work will inform the improvement of the imaging methods for early diagnosis of PTOA.
Publisher: Mary Ann Liebert Inc
Date: 18-03-2011
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.BIOMATERIALS.2014.06.038
Abstract: The osteoimmunomodulatory property of bone biomaterials is a vital property determining the in vivo fate of the implants. Endowing bone biomaterials with favorable osteoimmunomodulatory properties is of great importance in triggering desired immune response and thus supports the bone healing process. Magnesium (Mg) has been recognized as a revolutionary metal for applications in orthopedics due to it being biodegradable, biocompatible, and having osteoconductive properties. However, Mg's high rate of degradation leads to an excessive inflammatory response and this has restricted its application in bone tissue engineering. In this study, β-tricalcium phosphate (β-TCP) was used to coat Mg scaffolds in an effort to modulate the detrimental osteoimmunomodulatory properties of Mg scaffolds, due to the reported favorable osteoimmunomodulatory properties of β-TCP. It was noted that macrophages switched to the M2 extreme phenotype in response to the Mg-β-TCP scaffolds, which could be due to the inhibition of the toll like receptor (TLR) signaling pathway. VEGF and BMP2 were significantly upregulated in the macrophages exposed to Mg-β-TCP scaffolds, indicating pro-osteogenic properties of macrophages in β-TCP modified Mg scaffolds. This was further demonstrated by the macrophage-mediated osteogenic differentiation of bone marrow stromal cells (BMSCs). When BMSCs were stimulated by conditioned medium from macrophages cultured on Mg-β-TCP scaffolds, osteogenic differentiation of BMSCs was significantly enhanced whereas osteoclastogenesis was inhibited, as indicated by the downregualtion of MCSF, TRAP and inhibition of the RANKL/RANK system. These findings suggest that β-TCP coating of Mg scaffolds can modulate the scaffold's osteoimmunomodulatory properties, shift the immune microenvironment towards one that favors osteogenesis over osteoclastogenesis. Endowing bone biomaterials with favorable osteoimmunomodulatory properties can be a highly valuable strategy for the development or modification of advanced bone biomaterials.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 2021
Abstract: Melanoma is a serious malignant skin tumor. Effectively eliminating melanoma and healing after-surgical wounds are always challenges in clinical studies. To address these problems, we propose manganese-doped calcium silicate nanowire-incorporated alginate hydrogels (named MCSA hydrogels) for in situ photothermal ablation of melanoma followed by the wound healing process. The proposed MCSA hydrogel had controllable gelation properties, reasonable strength, and excellent bioactivity due to the incorporated calcium silicate nanowires as the in situ cross-linking agents and bioactive components. The doping of manganese into calcium silicate nanowires gave them excellent photothermal effects for eradicating melanoma effectively under near infrared (NIR) irradiation. Moreover, the synergistic effect of manganese and silicon in the MCSA hydrogel effectively promotes migration and proliferation of vascular endothelial cells and promotes angiogenesis. Hence, such bifunctional bioactive hydrogels could achieve combined functions of photothermal therapy and wound healing, showing great promise for melanoma therapy and tissue regeneration.
Publisher: Wiley
Date: 10-09-2018
Publisher: Mary Ann Liebert Inc
Date: 11-2005
Abstract: Cell attachment, expansion, and migration in three-dimensional biomaterials are crucial steps for effective delivery of osteogenic cells into bone defects. Complexes composed of vitronectin (VN), insulin-like growth factors (IGFs), and insulin growth factor-binding proteins (IGFBPs) have been reported to enhance cell attachment, proliferation, and migration in a variety of cell lines in vitro. The aim of this study was to examine whether prebound complexes of VN and IGFs +/- IGFBPs could facilitate human osteoblast serum-free expansion in vitro and enhance cell attachment, proliferation, and migration in three-dimensional biomaterial constructs. Human osteoblasts derived from alveolar bone chips and the established human osteoblast cell line Saos-2 were used. These cells were seeded on tissue culture plates and porous scaffolds of type I collagen sponges and polyglycolic acid (PGA), which had been coated with VN +/- IGFBP-5 +/- IGF-I. Cell attachment, proliferation, and migration were evaluated by cell counting, confocal microscopy, and scanning electron microscopy. The number of attached human osteoblasts was significantly higher in VN-coated polystyrene culture dishes. Furthermore, significant increases in cell proliferation were observed when growth factors were bound to these surfaces in the presence of VN. In the two scaffold materials examined, greater cell attachment was found in type I collagen sponges compared with PGA scaffolds. However, coating the scaffolds with complexes composed of VN + IGF-I or VN + IGFBP-5 + IGF-I enhanced cell attachment on PGA. Moreover, the presence of VN + IGFBP-5 + IGF-I resulted in significantly greater osteoblast migration into deep pore areas as compared with untreated scaffolds or scaffolds treated with fetal calf serum. These results demonstrated that complexes of VN + IGFBP-5 + IGF-I can be used to expand osteoblasts in vitro under serum-free conditions and enhance the attachment and migration of human osteoblasts in three-dimensional culture. This in turn suggests a potential application in surface modification of biomaterials for tissue reconstruction.
Publisher: IOP Publishing
Date: 31-01-2020
Abstract: After surgical resection for a bone tumor, the uncleared bone tumor cells can multiply and cause recurrence of the bone tumor. It is worthwhile to design a scaffold that kills the remaining bone tumor cells and repairs bone defects that were given rise to by surgical resection. Additionally, it is extremely important to consider the function of angiogenesis in the process of bone regeneration because the newly formed blood vessels can offer the nutrients for bone regeneration. In this work, a novel metal-organic framework Cu-TCPP nanosheets interface-structured β-tricalcium phosphate (TCP) (Cu-TCPP-TCP) scaffold was successfully prepared through integrating a 3D-printing technique with an in-situ growth method in a solvothermal system. Owing to the excellent photothermal effect of Cu-TCPP nanosheets, Cu-TCPP-TCP scaffolds that were illuminated by near-infrared (NIR) light demonstrated photothermal performance, which was well regulated through varying the contents of Cu-TCPP nanosheets, and the ambient humidity and power density of NIR light. When cultured with osteosarcoma cells, Cu-TCPP-TCP scaffolds killed a significant quantity of osteosarcoma cells through released heat energy after exposure to NIR light with power density 1.0 W cm
Publisher: CRC Press
Date: 22-03-2013
DOI: 10.1201/B13926-7
Publisher: Springer Science and Business Media LLC
Date: 06-03-2021
DOI: 10.1186/S13287-021-02227-7
Abstract: Growing evidence suggests that the pluripotent state of mesenchymal stem cells (MSCs) relies on specific local microenvironmental cues such as adhesion molecules and growth factors. Fibronectin (FN), fibroblast growth factor 2 (FGF2), and bone morphogenetic protein 4 (BMP4) are the key players in the regulation of stemness and lineage commitment of MSCs. Therefore, this study was designed to investigate the pluripotency and multilineage differentiation of bone marrow-derived MSCs (BMSCs) with the introduction of FN, FGF-2, and BMP4 and to identify the metabolic and proteomic cues involved in stemness maintenance. To elucidate the stemness of BMSCs when treated with FN, FGF-2, and BMP4, the pluripotency markers of OCT4, SOX2, and c-MYC in BMSCs were monitored by real-time PCR and/or western blot. The nuclear translocation of OCT4, SOX2, and c-MYC was investigated by immunofluorescence staining. Multilineage differentiation of the treated BMSCs was determined by relevant differentiation markers. To identify the molecular signatures of BMSC stemness, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and bioinformatics analysis were utilized to determine the metabolite and protein profiles associated with stem cell maintenance. Our results demonstrated that the expression of stemness markers decreased with BMSC passaging, and the manipulation of the microenvironment with fibronectin and growth factors (FGF2 and BMP4) can significantly improve BMSC stemness. Of note, we revealed 7 differentially expressed metabolites, the target genes of these metabolites may have important implications in the maintenance of BMSCs through their effects on metabolic activity, energy production, and potentially protein production. We also identified 21 differentially abundant proteins, which involved in multiple pathways, including metabolic, autophagy-related, and signaling pathways regulating the pluripotency of stem cells. Additionally, bioinformatics analysis comfirned the correlation between metabolic and proteomic profiling, suggesting that the importance of metabolism and proteome networks and their reciprocal communication in the preservation of stemness. These results indicate that the culture environment supplemented with the culture cocktail (FN, FGF2, and BMP4) plays an essential role in shaping the pluripotent state of BMSCs. Both the metabolism and proteome networks are involved in this process and the modulation of cell-fate decision making. All these findings may contribute to the application of MSCs for regenerative medicine.
Publisher: CRC Press
Date: 22-03-2013
DOI: 10.1201/B13926-6
Publisher: Informa UK Limited
Date: 22-02-2021
Publisher: Mary Ann Liebert Inc
Date: 10-2014
Publisher: Springer Science and Business Media LLC
Date: 11-09-2013
DOI: 10.1007/S00109-012-0953-5
Abstract: We hypothesised that a potentially disease-modifying osteoarthritis (OA) drug such as hyaluronic acid (HA) given in combination with anti-inflammatory signalling agents such as mitogen-activated protein kinase kinase-extracellular signal-regulated kinase (MEK-ERK) signalling inhibitor (U0126) could result in additive or synergistic effects on preventing the degeneration of articular cartilage. Chondrocyte differentiation and hypertrophy were evaluated using human OA primary cells treated with either HA or U0126, or the combination of HA + U0126. Cartilage degeneration in menisectomy (MSX) induced rat OA model was investigated by intra-articular delivery of either HA or U0126, or the combination of HA + U0126. Histology, immunostaining, RT-qPCR, Western blotting and zymography were performed to assess the expression of cartilage matrix proteins and hypertrophic markers. Phosphorylated ERK (pERK)1/2-positive chondrocytes were significantly higher in OA s les compared with those in healthy control suggesting the pathological role of that pathway in OA. It was noted that HA + U0126 significantly reduced the levels of pERK, chondrocyte hypertrophic markers (COL10 and RUNX2) and degenerative markers (ADAMTs5 and MMP-13), however, increased the levels of chondrogenic markers (COL2) compared to untreated or the application of HA or U0126 alone. In agreement with the results in vitro, intra-articular delivery of HA + U0126 showed significant therapeutic improvement of cartilage in rat MSX OA model compared with untreated or the application of HA or U0126 alone. Our study suggests that the combination of HA and MEK-ERK inhibition has a synergistic effect on preventing cartilage degeneration.
Publisher: Springer Science and Business Media LLC
Date: 05-03-2016
DOI: 10.1007/S00223-016-0125-7
Abstract: This study aimed to identify the microRNAs associated with sclerotic status of subchondral bone in the pathogenesis of osteoarthritis (OA). Total RNA was extracted from non-sclerotic and sclerotic OA subchondral bone from patients undergoing knee replacement surgeries. miRCURY™ LNA miRNA chip and qRT-PCR were used to profile and validate differential microRNA expression. In addition, we further confirmed profiles of altered miRNAs in an OA rat meniscectomy animal model and their putative targets of the miRNAs were predicted using ingenuity (IPA) software. Finally, five short-listed miRNAs were reactivated by transient in vitro overexpression (miRNA mimics) in subchondral bone osteoblasts and their phenotypes were assessed. Functional screening identified 30 differentiated miRNAs in sclerotic subchondral bone compared to non-sclerotic bone of OA patients. Data integration resulted in confirmation of the eight miRNAs, with aberrant expression in independent human OA bone s le set. In silico analysis (IPA) identified 732 mRNA transcripts as putative targets of the eight altered miRNAs, of which twenty genes were validated to be differentially expressed in sclerotic compared to non-sclerotic bone s les. Out of eight dysregulated miRNA's, five of them showed consistent time-dependent downregulation in a rat OA model. Furthermore, synthetic miR-199a-3p, miR-199a-5p, miR-590-5p, and miR-211-5p mimics rescued the abnormal osteoarthritic subchondral bone osteoblast gene expression and mineralization. We have identified four novel miRNAs that play important roles in subchondral bone pathogenesis in OA. Additional studies are required to develop these miRNAs into therapeutic modalities for OA.
Publisher: Wiley
Date: 21-11-2011
Publisher: Mary Ann Liebert Inc
Date: 12-2013
Publisher: Wiley
Date: 05-01-2011
DOI: 10.1002/JBM.B.31779
Abstract: Poly(lactide-co-glycolide) (PLGA) beads have been widely studied as a potential drug rotein carrier. The main shortcomings of PLGA beads are that they lack bioactivity and controllable drug-delivery ability, and their acidic degradation by-products can lead to pH decrease in the vicinity of the implants. Akermanite (AK) (Ca(2) MgSi(2) O(7) ) is a novel bioactive ceramic which has shown excellent bioactivity and degradation in vivo. This study aimed to incorporate AK to PLGA beads to improve the physiochemical, drug-delivery, and biological properties of PLGA beads. The microstructure of beads was characterized by SEM. The effect of AK incorporating into PLGA beads on the mechanical strength, apatite-formation ability, the loading and release of BSA, and the proliferation, and differentiation of bone marrow stromal cells (BMSCs) was investigated. The results showed that the incorporation of AK into PLGA beads altered the anisotropic microporous structure into homogenous one and improved their compressive strength and apatite-formation ability in simulated body fluids (SBF). AK neutralized the acidic products from PLGA beads, leading to stable pH value of 7.4 in biological environment. AK led to a sustainable and controllable release of bovine serum albumin (BSA) in PLGA beads. The incorporation of AK into PLGA beads enhanced the proliferation and alkaline phosphatase activity of BMSCs. This study implies that the incorporation of AK into PLGA beads is a promising method to enhance their physiochemical and biological property. AK/PLGA composite beads are a potential bioactive drug-delivery system for bone tissue repair.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.ACTBIO.2012.06.023
Abstract: To achieve the ultimate goal of periodontal tissue engineering, it is of great importance to develop bioactive scaffolds which can stimulate the osteogenic/cementogenic differentiation of periodontal ligament cells (PDLCs) for the favorable regeneration of alveolar bone, root cementum and periodontal ligament. Strontium (Sr) and Sr-containing biomaterials have been found to induce osteoblast activity. However, there has been no systematic report about the interaction between Sr or Sr-containing biomaterials and PDLCs for periodontal tissue engineering. The aims of this study were to prepare Sr-containing mesoporous bioactive glass (Sr-MBG) scaffolds and investigate whether the addition of Sr could stimulate osteogenic/cementogenic differentiation of PDLCs in a tissue-engineering scaffold system. The composition, microstructure and mesopore properties (specific surface area, nanopore volume and nanopore distribution) of Sr-MBG scaffolds were characterized. The proliferation, alkaline phosphatase (ALP) activity and osteogenesis/cementogenesis-related gene expression (ALP, Runx2, Col I, OPN and CEMP1) of PDLCs on different kinds of Sr-MBG scaffolds were systematically investigated. The results show that Sr plays an important role in influencing the mesoporous structure of MBG scaffolds in which high contents of Sr decreased the well-ordered mesopores as well as their surface area ore volume. Sr(2+) ions could be released from Sr-MBG scaffolds in a controlled way. The incorporation of Sr into MBG scaffolds has significantly stimulated ALP activity and osteogenesis/cementogenesis-related gene expression of PDLCs. Furthermore, Sr-MBG scaffolds in a simulated body fluid environment still maintained excellent apatite-mineralization ability. The study suggests that the incorporation of Sr into MBG scaffolds is a viable way to stimulate the biological response of PDLCs. Sr-MBG scaffolds are a promising bioactive material for periodontal tissue-engineering applications.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2016
DOI: 10.1007/S11926-016-0605-9
Abstract: Osteoarthritis (OA) is the most common musculoskeletal disease, affecting nearly 25 % of the world population (WHO reports), leading to pain and disability. There are as yet no clinically proven therapies to halt OA onset or progression the development of such therapies is, therefore, a national as well as international research priority. Obesity-related metabolic syndrome has been identified as the most significant, but also an entirely preventable risk factor for OA however, the mechanisms underlying this link remain unclear. We have examined the available literature linking OA and metabolic syndrome. The two conditions have a shared pathogenesis in which chronic low-grade inflammation of affected tissues is recognized as a major factor that is associated with systemic inflammation. In addition, the occurrence of metabolic syndrome appears to alter systemic and local pro-inflammatory cytokines that are also related to the development of OA-like pathologies. Recent findings highlight the importance not only of the elevated number of macrophage in inflamed synovium but also the activation and lification of the inflammatory state and other pathological changes. The role of local inflammation on the synovium is now considered to be a pharmacological target against which to aim disease-modifying drugs. In this review, we evaluate evidence linking OA, synovitis and metabolic syndrome and discuss the merits of targeting macrophage activation as a valid treatment option for OA.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1TB01517F
Abstract: Zn-doped bioactive glass (BGz) micro–nano spheres for dental pulp capping to control infection and inflammation and promote tissue regeneration.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Wiley
Date: 20-03-2020
Publisher: Wiley
Date: 14-06-2012
DOI: 10.1002/JBM.A.34246
Abstract: Strontium (Sr), Zinc (Zn), magnesium (Mg), and silicon (Si) are reported to be essential trace elements for the growth and mineralization of bone. We speculated that the combination of these bioactive elements in bioceramics may be effective to regulate the osteogenic property of bone-forming cells. In this study, two Sr-containing silicate bioceramics, Sr(2)ZnSi(2)O(7) (SZS) and Sr(2)MgSi(2)O(7) (SMS), were prepared. The biological response of human bone marrow mesenchymal stem cells (BMSCs) to the two bioceramics (in the forms of powders and dense ceramic bulks) was systematically studied. In powder form, the effect of powder extracts on the viability and alkaline phosphatase (ALP) activity of BMSCs was investigated. In ceramic disc form, both direct and indirect coculture of BMSCs with ceramic discs were used to investigate their biological response, including attachment, proliferation, ALP activity, and bone-related genes expression. Beta-tricalcium phosphate (β-TCP) and akermanite (Ca(2)MgSi(2)O(7), CMS) were used as control materials. The results showed that the Sr, Zn, and Si (or Sr, Mg, and Si)-containing ionic products from SZS and SMS powders enhanced ALP activity of BMSCs, compared to those from β-TCP. Both SZS and SMS ceramic discs supported the growth of BMSCs, and most importantly, significantly enhanced the ALP activity and bone-related genes expression of BMSCs as compared to β-TCP. The results suggest that the specific combination of bioactive ions (Sr, Zn, Si, e.g.) in bioceramics is a viable way to improve the biological performance of biomaterials, and the form of materials and surface properties were nonnegligible factors to influence cell response.
Publisher: Elsevier BV
Date: 12-2022
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C8TB01675E
Abstract: Percutaneous coronary intervention with stenting is the most widely adopted surgical technique for the treatment of coronary disease.
Publisher: Zoological Society of Japan
Date: 12-2013
DOI: 10.2108/ZSJ.30.1032
Abstract: Autologous bone marrow-derived mesenchymal stem cell (BMSCs)-based therapies show great potential in regenerative medicine. However, long-term storage and preservation of BMSCs for clinical use is still a great clinical challenge. The present study aimed to analyze the effect of long-term cryopreservation on the regenerative ability of BMSCs. After cryopreservation of BMSCs from beagle dogs for three years, cell viability, and quantitative analysis of alkaline phosphatase (ALP) activity, surface adherence, and mineralized nodule formation were analyzed. BMSCs in cell-scaffold complex were then implanted into nude mice. There was no significant difference in cell viability and ALP activity between osteogenic differentiation and non-osteogenic differentiation of BMSCs, and BMSCs in cell-scaffold complex retained osteogenic differentiation ability in vivo. These results indicate that long-term cryopreserved BMSCs maintain their have capacity to contribute to regeneration.
Publisher: Informa UK Limited
Date: 2200
DOI: 10.1080/03008200600646360
Abstract: A biological and embryological bone induction from epithelial-mesenchymal cell interactions has been noticed in some developing tissues. However, the mechanism for bone formation induced by the epithelial-mesenchymal cell interactions is not clear. The aim of our study was to reveal the role of laminin, vascular endothelial growth factor (VEGF), and bone matrix proteins in mesenchymal cell differentiation during uroepithelial bone induction using a well-established canine model. In this model, a myoperitoneal muscle flap from the abdominal rectus sheath was transplanted into the bladder wall. After 6 weeks, the bladder s les were removed and assessed by histology and immunohistochemistry. This study demonstrated that bone formation occurred in two different directions with two distinct mechanisms. We noted that bone-forming cells in two types of bone formation derived from mesenchymal stem cell differentiation induced either from uroepithelium or bone autoinduction. Laminin was only expressed in peripheral regions of uroepithelium bone formation. Type II collagen was expressed both intracellularly and extracellularly around hypertrophic chondrocytes, whereas VEGF was mostly expressed in proliferating chondrocytes. This study indicates that components in basement membrane like laminin play a role in transitional epithelium-induced differentiation of mesenchymal cells to chondrocytes in muscle tissue. The sequential expression of bone matrix proteins by differentiated osteogenetic cells indicates a subsequent sequence of bone autoinduction.
Publisher: Springer Science and Business Media LLC
Date: 03-07-2018
Publisher: Ivyspring International Publisher
Date: 2012
DOI: 10.7150/IJBS.4221
Publisher: Elsevier BV
Date: 08-2012
Publisher: Wiley
Date: 26-12-2019
Abstract: Osteomyelitis is an inflammatory bone disease caused by infection microorganisms which leads to progressive bone destruction and loss. Drug resistance and inflammatory damage make it urgent to develop new dual-functional therapies. Based on the powerful bactericidal effect of monocyte/macrophage cells by nature, a functional monocyte with programed anti-inflammatory ability is promising for osteomyelitis treatment. Herein, gold nanocage (GNC)-modified monocytes are developed which contain aspirin to realize the controlled antibacterial and anti-inflammatory process for bone infection treatment effectively. Aspirin@GNC-laden monocytes inherit the biological functions of origin monocytes such as chemotaxis to bacteria, differentiation potential, and phagocytic ability. The controlled release of aspirin from GNC has a beneficial effect on improving the rate and amount of bone regeneration after the anti-infection stage due to its ability to suppress the activity of natural immunity and induce osteoblast differentiation during the treatment of osteomyelitis. The present work described here is the first to utilize living monocytes to achieve a dual effect to antibacteria and anti-inflammation in a time-oriented and programed way, and provides an inspiration for future therapy based on this concept.
Publisher: Elsevier BV
Date: 06-2022
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6TB02255C
Abstract: Calcium phosphates (CAPs) can be produced from either biologically sourced materials or mineral deposits.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB00683K
Abstract: Angiogenesis represents a major focus for novel therapeutic approaches to the treatment and management of multiple pathological conditions, such as ischemic heart disease and critical-sized bone defect.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.BIOMATERIALS.2022.121684
Abstract: Osseointegration of implants is a complex physiological process that requires temporal and spatial regulation of immune responses, angiogenesis, and osteogenesis. To achieve efficient and long-term osseointegration, type I collagen (COL1) decorated nanoporous network was developed on titanium substrates via alkali treatment, polydopamine coating, and layer-by-layer (LBL) self-assembly. It was noted that the simple physisorbed COL1 could be easily desorbed from the nanostructured surface, however, multilayer COL1 constructed by polydopamine and LBL self-assembly obscured the nanoporous network of the alkali-treated titanium surfaces. Interestingly, the nanostructured surface covalently immobilized with COL1 (T-ADC) could timely convert macrophages (MΦs) from pro-inflammatory M1 to pro-healing M2 phenotype, generating a beneficial osteoimmune microenvironment and promoting angio/osteo-genesis. RNA sequencing revealed that the nanostructure and COL1 could synergistically activate RhoA/ROCK, PI3K-AKT, and classical MAPK signaling pathways in MΦs to sustain the cell cycle, and trigger autocrine feedback-mediated JAK-STAT and FoxO signaling pathways, which in turn motivated autophagy and oxidative stress resistance and attenuated lipopolysaccharide-induced Toll-like receptor signaling pathway and its downstream NF-κB and JNK 38 MAPK signaling cascades, leading to the inhibition of inflammation and osteoclastic-related gene expression of MΦs. Simultaneously, T-ADC prominently facilitated angiogenesis of endothelial cells and osteogenesis of osteoblasts as well as their cross-talks, further highlighting synergistically positive effects of the nanostructure and COL1 on osseointegration. In vivo experiments revealed that T-ADC could induce abundant new bone mass and ameliorative osseointegration, corroborating the in vitro results. The study elucidated that the COL1 decorated nanoporous network on titanium surfaces could significantly regulate early inflammatory reaction and subsequent angio/osteo-genesis processes, resulting in favorable osseointegration.
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/731039
Abstract: Periodontitis is an inflammatory disease characterized by periodontal pocket formation and alveolar bone resorption. Periodontal bone resorption is induced by osteoclasts and receptor activator of nuclear factor- κ B ligand (RANKL) which is an essential and central regulator of osteoclast development and osteoclast function. Therefore, RANKL plays a critical role in periodontal bone resorption. In this review, we have summarized the sources of RANKL in periodontal disease and explored which factors may regulate RANKL expression in this disease.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2JM30566F
Publisher: Wiley
Date: 08-2002
DOI: 10.1034/J.1600-0765.2002.01624.X
Abstract: Cell-surface proteoglycans participate in several biological functions including interactions with adhesion molecules, growth factors and a variety of other effector molecules. Accordingly, these molecules play a central role in various aspects of cell-cell and cell-matrix interactions. To investigate the expression and distribution of the cell surface proteoglycans, syndecan-1 and -2, during periodontal wound healing, immunohistochemical analyses were carried out using monoclonal antibodies against syndecan-1, or -2 core proteins. Both syndecan-1 and -2 were expressed and distributed differentially at various stages of early inflammatory cell infiltration, granulation tissue formation, and tissue remodeling in periodontal wound healing. Expression of syndecan-1 was noted in inflammatory cells within and around the fibrin clots during the earliest stages of inflammatory cells infiltration. During granulation tissue formation it was noted in fibroblast-like cells and newly formed blood vessels. Syndecan-1 was not seen in newly formed bone or cementum matrix at any of the time periods studied. Syndecan-1 expression was generally less during the late stages of wound healing but was markedly expressed in cells that were close to the repairing junctional epithelium. In contrast, syndecan-2 expression and distribution was not evident at the early stages of inflammatory cell infiltration. During the formation of granulation tissue and subsequent tissue remodeling, syndecan-2 was expressed extracellularly in the newly formed fibrils which were oriented toward the root surface. Syndecan-2 was found to be significantly expressed on cells that were close to the root surface and within the matrix of repaired cementum covering root dentin as well as at the alveolar bone edge. These findings indicate that syndecan-1 and -2 may have distinctive functions during wound healing of the periodontium. The appearance of syndecan-1 may involve both cell-cell and cell-matrix interactions, while syndecan-2 showed a predilection to associate with cell-matrix interactions during hard tissue formation.
Publisher: Frontiers Media SA
Date: 25-06-2019
Publisher: Wiley
Date: 09-08-2005
DOI: 10.1111/J.1600-0765.2005.00823.X
Abstract: The epithelial cell rests of Malassez (ERM) are derived from Hertwig's epithelial root sheath (HERS). During development the cells of HERS deposit a variety of molecules on the newly forming root surface. The possibility that ERM retain this potential after root development is completed and secrete bone or cementum-related proteins needs to be investigated. The purpose of this study was to determine the expression of the non-collagenous proteins osteopontin (OPN) and bone sialoprotein (BSP) by cells derived from the epithelial cell rests of porcine periodontium. ERM and fibroblasts were cultured from porcine periodontal ligament. The cells were identified and characterized using transmission electron microscopy, immunohistochemistry, western blot analysis of proteins, reverse transcription-polymerase chain reaction and ability to form mineralized nodules in culture. In particular the expression of the mineralized tissue-related proteins, BSP and OPN, was studied. Cells from porcine periodontal ligaments were successfully cultured separated and characterized as being of either an epithelial or fibroblastic phenotype. Although the ERM did not form mineralized nodules in culture, they did express a significant amount of mRNA for OPN. The results from this study provide evidence that ERM express mRNA for at least one bone/cementum-related protein. Whether this function would be consistent with a role for ERM in tissue formation, inflammation and regeneration remains to be established.
Publisher: The Journal of Rheumatology
Date: 15-01-2012
Abstract: Degradative enzymes, such as A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinases (MMP), play key roles in development of osteoarthritis (OA). We investigated if crosstalk between subchondral bone osteoblasts (SBO) and articular cartilage chondrocytes (ACC) in OA alters the expression and regulation of ADAMTS5, ADAMTS4, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-13, and also tested the possible involvement of mitogen-activated protein kinase (MAPK) signaling pathway during this process. ACC and SBO were isolated from normal and OA patients. An in vitro coculture model was developed to study the regulation of ADAMTS and MMP under normal and OA joint crosstalk conditions. The MAPK-ERK inhibitor PD98059 was applied to delineate the involvement of specific pathways during this interaction process. Indirect coculture of OA SBO with normal ACC resulted in significantly increased expression of ADAMTS5, ADAMTS4, MMP-2, MMP-3, and MMP-9 in ACC, whereas coculture of OA ACC led to increased MMP-1 and MMP-2 expression in normal SBO. Upregulation of ADAMTS and MMP under these conditions was correlated with activation of the MAPK-ERK1/2 signaling pathway, and addition of the MAPK-ERK inhibitor PD98059 reversed the overexpression of ADAMTS and MMP in cocultures. These results add to the evidence that in human OA, altered bidirectional signals between SBO and ACC significantly influence the critical features of both cartilage and bone by producing abnormal levels of ADAMTS and MMP. We have demonstrated for the first time that this altered crosstalk was mediated by the phosphorylation of MAPK-ERK1/2 signaling pathway.
Publisher: Springer New York
Date: 2019
DOI: 10.1007/978-1-4939-9769-5_4
Abstract: Exosomes are small endosome-derived lipid nanoparticles (50-120 nm in diameter), actively secreted by exocytosis in most living cells. Recently, there is a growing interest of research focused on studying the exosome functions and to understand ways to use them for therapeutic applications in a wide variety of disorders, such as cancer, cardiovascular, neurodegenerative, and musculoskeletal diseases. Recently, a number of techniques have been developed for the isolation of exosomes such as ultracentrifugation, micro-filtration centrifugation, gradient centrifugation, and size-exclusion chromatography. In this chapter, we reveal the protocol and key insights into the isolation, purification, and characterization of exosomes using ultracentrifugation method.
Publisher: Wiley
Date: 13-10-2017
Publisher: Springer Science and Business Media LLC
Date: 27-10-2014
DOI: 10.1007/S11010-013-1840-2
Abstract: Recently, it has been suggested osteocytes control the activities of bone formation (osteoblasts) and resorption (osteoclast), indicating their important regulatory role in bone remodelling. However, to date, the role of osteocytes in controlling bone vascularisation remains unknown. Our aim was to investigate the interaction between endothelial cells and osteocytes and to explore the possible molecular mechanisms during angiogenesis. To model osteocyte/endothelial cell interactions, we co-cultured osteocyte cell line (MLOY4) with endothelial cell line (HUVECs). Co-cultures were performed in 1:1 mixture of osteocytes and endothelial cells or by using the conditioned media (CM) transfer method. Real-time cell migration of HUVECs was measured with the transwell migration assay and xCELLigence system. Expression levels of angiogenesis-related genes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of vascular endothelial growth factor (VEGF) and mitogen-activated phosphorylated kinase (MAPK) signaling were monitored by western blotting using relevant antibodies and inhibitors. During the bone formation, it was noted that osteocyte dendritic processes were closely connected to the blood vessels. The CM generated from MLOY4 cells-activated proliferation, migration, tube-like structure formation, and upregulation of angiogenic genes in endothelial cells suggesting that secretory factor(s) from osteocytes could be responsible for angiogenesis. Furthermore, we identified that VEGF secreted from MLOY4-activated VEGFR2-MAPK-ERK-signaling pathways in HUVECs. Inhibiting VEGF and/or MAPK-ERK pathways abrogated osteocyte-mediated angiogenesis in HUVEC cells. Our data suggest an important role of osteocytes in regulating angiogenesis.
Publisher: Wiley
Date: 17-12-2013
DOI: 10.1002/JCB.24362
Abstract: Osteoarthritis is characterized by degenerative alterations of articular cartilage including both the degradation of extracellular matrix and the death of chondrocytes. The PI3K/Akt pathway has been demonstrated to involve in both processes. Inhibition of its downstream target NF-kB reduces the degradation of extracellular matrix via decreased production of matrix metalloproteinases while inhibition of mTOR increased autophagy to reduce chondrocyte death. However, mTOR feedback inhibits the activity of the PI3K/Akt pathway and inhibition of mTOR could result in increased activity of the PI3K/Akt/NF-kB pathway. We proposed that the use of dual inhibitors of PI3K and mTOR could be a promising approach to more efficiently inhibit the PI3K/Akt pathway than rapamycin or PI3K inhibitor alone and produce better treatment outcome.
Publisher: The Endocrine Society
Date: 13-06-2022
Abstract: Inflammation is a body’s response to remove harmful stimuli and heal tissue damage, which is involved in various physiology and pathophysiology conditions. If dysregulated, inflammation may lead to significant negative impacts. Growth hormone (GH) has been shown responsible for not only body growth but also critical in the modulation of inflammation. In this review, we summarize the current clinical and animal studies about the complex and critical role of GH in inflammation. Briefly, GH excess or deficiency may lead to pathological inflammatory status. In inflammatory diseases, GH may serve as an inflammatory modulator to control the disease progression and promote disease resolution. The detailed mechanisms and signaling pathways of GH on inflammation, with a focus on the modulation of macrophage polarization, are carefully discussed with potential direction for future investigations.
Publisher: Wiley
Date: 21-02-2018
DOI: 10.1002/JBMR.3396
Abstract: Accumulating evidence indicates that the immune and skeletal systems interact with each other through various regulators during the osteoclastogenic process. Among these regulators, the bioactive lipid sphingosine-1-phosphate (S1P), which is synthesized by sphingosine kinase 1/2 (SPHK1/2), has recently been recognized to play a role in immunity and bone remodeling through its receptor sphingosine-1-phosphate receptor 1 (S1PR1). However, little is known regarding the potential role of S1PR1 signaling in inflammatory bone loss. We observed that SPHK1 and S1PR1 were upregulated in human apical periodontitis, accompanied by macrophage infiltration and enhanced expression of receptor activator of NF-κB ligand (RANKL, an indispensable factor in osteoclastogenesis and bone resorption) and increased numbers of S1PR1-RANKL double-positive cells in lesion tissues. Using an in vitro co-culture model of macrophages and bone marrow stromal cells (BMSCs), it was revealed that in the presence of lipopolysaccharide (LPS) stimulation, macrophages could significantly induce SPHK1 activity, which resulted in activated S1PR1 in BMSCs. The activated S1P-S1PR1 signaling was responsible for the increased RANKL production in BMSCs, as S1PR1-blockage abolished this effect. Applying a potent S1P-S1PR1 signaling modulator, Fingolimod (FTY720), in a Wistar rat apical periodontitis model effectively prevented bone lesions in vivo via downregulation of RANKL production, osteoclastogenesis, and bone resorption. Our data unveiled the regulatory role of SPHK1-S1PR1-RANKL axis in inflammatory bone lesions and proposed a potential therapeutic intervention by targeting this cell-signaling pathway to prevent bone loss. © 2018 American Society for Bone and Mineral Research.
Publisher: Wiley
Date: 05-2020
Publisher: Frontiers Media SA
Date: 28-04-2022
DOI: 10.3389/FMATS.2022.612052
Abstract: It is presently difficult to achieve dental pulp vitality maintenance and regeneration in adult teeth. Dentin destruction results in the exposure of the dental pulp tissue to infectious oral environments, thereby triggering continuous severe pulp inflammation that impedes the self-regenerative capacity of the pulp. For these reasons, the regeneration of dentin bridges to block pulp tissue from the oral environment is an indispensable step. Nevertheless, this goal is difficult to achieve using present strategies, because the importance of immunoregulation in the pulp inflammatory microenvironment has been ignored. In our previous study, we found that the nanomaterial dihydrolipoic acid-functionalized gold nanoclusters (DHLA-AuNCs) efficiently regulated inflammatory responses in microglia (resident macrophages in the central nervous system), suggesting that DHLA-AuNCs may induce dentin bridge regeneration by regulating dental pulp macrophage responses. In the present study, we found that DHLA-AuNCs inhibited the M1 phenotype while promoting the M2 phenotype in macrophages in inflammatory conditions in vitro . This regulation of the inflammatory environment in dental pulp enhanced the differentiation of human dental pulp stromal cells (hDPC) toward odontoblasts, a beneficial effect on dentin regeneration. DHLA-AuNCs also had a direct role in the differentiation and mineralization of hDPC. These findings suggest that DHLA-AuNCs facilitate dentin regeneration through both efficient immunomodulation and direct induction of stromal cell differentiation/mineralization, providing a potential therapeutic nanomaterial for dentin bridge regeneration, effects that would be beneficial for dental pulp regeneration.
Publisher: Mary Ann Liebert Inc
Date: 09-2018
Publisher: Wiley
Date: 08-2000
DOI: 10.1034/J.1600-0765.2000.035004214.X
Abstract: Cell-surface proteoglycans participate in several biological functions such as cell cell and cell-matrix interactions, cell adhesion, the binding to various growth factors as co-receptors and repair. To understand better the expression and distribution of cell-surface proteoglycans in the periodontal tissues, an immunohistochemical evaluation of the normal Lewis rat molar periodontium using panels of antibodies for syndecan-1, -2, -4, glypican and betaglycan was carried out. Our results demonstrated the expression and distribution of all proteoglycans in the suprabasal gingival epithelium, soft and hard connective tissues. Both cellular and matrix localization was evident within the various periodontal compartments. The presence of these cell-surface proteoglycans indicates the potential for roles in the process of tissue homeostasis, repair or regeneration in periodontium of which each function requires further study.
Publisher: Mary Ann Liebert Inc
Date: 30-04-2021
Publisher: Mary Ann Liebert Inc
Date: 08-2011
DOI: 10.1089/TEN.TEC.2010.0453
Abstract: For a scaffold material to be considered effective and efficient for tissue engineering, it should be biocompatible and bioinductive. Silk fiber is a natural biocompatible material suitable for scaffold fabrication however, silk is tissue conductive and lacks tissue-inductive properties. One proposed method to make the scaffold tissue inductive is to introduce plasmids or viruses encoding a specific growth factor into the scaffold. In this study, we constructed adenoviruses encoding bone morphogenetic protein-7 (BMP-7) and incorporated these into silk scaffolds. The osteoinductive and new bone formation properties of these constructs were assessed in vivo in a critical-sized skull defect animal model. Silk fibroin scaffolds containing adenovirus particles coding BMP-7 were prepared. The release of the adenovirus particles from the scaffolds was quantified by tissue-culture infective dose (TCID50), and the bioactivity of the released viruses was evaluated on human bone marrow mesenchymal stromal cells (BMSCs). To demonstrate the in vivo bone forming ability of the virus-carrying silk fibroin scaffold, the scaffold constructs were implanted into calvarial defects in SCID mice. In vitro studies demonstrated that the virus-carrying silk fibroin scaffold released virus particles over a 3-week period while preserving their bioactivity. In vivo test of the scaffold constructs in critical-sized skull defect areas revealed that silk scaffolds were capable of delivering the adenovirus encoding BMP-7, resulting in significantly enhanced new bone formation. Silk scaffolds carrying BMP-7 encoding adenoviruses can effectively transfect cells and enhance both in vitro and in vivo osteogenesis. The findings of this study indicate that silk fibroin is a promising biomaterial for gene delivery to repair critical-sized bone defects.
Publisher: Frontiers Media SA
Date: 02-08-2021
DOI: 10.3389/FCHEM.2021.699802
Abstract: Background: As a wound dressing and barrier membrane, surface modification of polycaprolactone (PCL) is needed in order to achieve better biological activities. Exosomes derived from mesenchymal stem cells (MSCs) hold significant tissue regeneration promise. Silver nanoparticles (Ag) have been suggested as the surface modification technique for various medical devices. Materials and Methods: Ag and human bone marrow MSC (hBMSC)-derived exosomes (MSCs-exo) were used to modify the PCL scaffold. The impact of different scaffolds on immune cells and MSC proliferation and differentiation was further evaluated. Results: MSCs-exo exhibited cup-shaped morphology with a diameter around 100 nm. MSCs-exo were enriched with exosome marker CD81 and showed good internalization into recipient cells. 200 ng/ml Ag nanoparticles and MSCs-exo were further used to modify the PCL scaffold. The internalization study further indicated a similar releasing pattern of exosomes from Ag/MSCs-exo hybrid scaffolds into RAW264.7 and hBMSCs at 12 and 24 h, respectively. Macrophages play an important role during different stages of bone regeneration. The MTT and confocal microscopy study demonstrated no significant toxicity of exosome and/or Ag hybrid scaffolds for macrophages and MSCs. Inflammatory macrophages were further used to mimic the inflammatory environment. A mixed population of elongated and round morphology was noted in the exosome and Ag hybrid group, in which the proinflammatory genes and secretion of IL-6 and TNF-α were significantly reduced. In addition, the exosome and Ag hybrid scaffolds could significantly boost the osteogenic differentiation of hBMSCs. Discussion: This study highlights the possibility of using Ag nanoparticles and MSCs-exo to modify the PCL scaffold, thus providing new insight into the development of the novel immunomodulatory biomembrane.
Publisher: Wiley
Date: 15-01-2022
Publisher: Trans Tech Publications, Ltd.
Date: 07-2008
DOI: 10.4028/WWW.SCIENTIFIC.NET/JBBTE.1.99
Abstract: The limitations of autogenic, allogenic and xenogenic grafting methods have led to the development of synthetic grafts as an alternative. The aim of this study was to manufacture highly porous and well interconnected hydroxyapatite scaffolds and modify them with a poly(lactic-co-glycolic acid) (PLGA)-bioactive glass composite coating to achieve mechanical properties close to those of natural cancellous bones. In this study, hydroxyapatite scaffolds were prepared from a calcium phosphate cement (CPC) powder and cell culture using fibroblast cells was done to examine the cytotoxicity of the materials used for the scaffolds. The average pore size of the scaffolds was found to be 650μm and the total porosity was about 80%. The hydroxyapatite scaffolds without the coating had a mean compressive strength and a mean compressive modulus of 0.74 MPa and 20.46 MPa, respectively, which were in contrast to those of the scaffolds coated with the PLGA-bioacitve glass composite material (1.36 MPa and 24.58 MPa, respectively). The fibroblast cells were observed to proliferate well on the PLGA-bioactive glass coated scaffolds. The cells had also penetrated into the scaffold to a depth of approximately 2mm. Thus the scaffolds fabricated in this study exhibited a favourable porous structure and good cell response which are desirable for bone tissue engineering.
Publisher: Elsevier BV
Date: 08-2020
Publisher: IEEE
Date: 11-2008
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8RA02072H
Abstract: Microsphere based drug delivery systems show great advantages for tissue engineering.
Publisher: Wiley
Date: 04-05-2011
DOI: 10.1002/JBM.A.33092
Abstract: Poly(lactide-co-glycolide) (PLGA) microspheres have been used for regenerative medicine due to their ability for drug delivery and generally good biocompatibility, but they lack adequate bioactivity for bone repair application. CaSiO₃ (CS) has been proposed as a new class of material suitable for bone tissue repair due to its excellent bioactivity. In this study, we set out to incorporate CS into PLGA microspheres to investigate how the phase structure (amorphous and crystal) of CS influences the in vitro and in vivo bioactivity of the composite microspheres, with a view to the application for bone regeneration. X-ray diffraction (XRD), N₂ adsorption-desorption analysis, and scanning electron microscopy (SEM) were used to analyze the phase structure, surface area ore volume, and microstructure of amorphous CS (aCS) and crystal CS (cCS), as well as their composite microspheres. The in vitro bioactivity of aCS and cCS-PLGA microspheres was evaluated by investigating their apatite-mineralization ability in simulated body fluids (SBF) and the viability of human bone mesenchymal stem cells (BMSCs). The in vivo bioactivity was investigated by measuring their de novo bone-formation ability. The results showed that the incorporation of both aCS and cCS enhanced the in vitro and in vivo bioactivity of PLGA microspheres. cCS/PLGA microspheres improved better in vitro BMSC viability and de novo bone-formation ability in vivo, compared to aCS/PLGA microspheres. Our study indicates that controlling the phase structure of CS is a promising method to modulate the bioactivity of polymer microsphere system for potential bone tissue regeneration.
Publisher: MDPI AG
Date: 19-01-2023
DOI: 10.3390/JFB14020056
Abstract: Bone is capable of adjusting size, shape, and quality to maintain its strength, toughness, and stiffness and to meet different needs of the body through continuous remodeling. The balance of bone homeostasis is orchestrated by interactions among different types of cells (mainly osteoblasts and osteoclasts), extracellular matrix, the surrounding biological milieus, and waste products from cell metabolisms. Inorganic ions liberated into the localized microenvironment during bone matrix degradation not only form apatite crystals as components or enter blood circulation to meet other bodily needs but also alter cellular activities as molecular modulators. The osteoinductive potential of inorganic motifs of bone has been gradually understood since the last century. Still, few have considered the naturally generated ionic microenvironment’s biological roles in bone remodeling. It is believed that a better understanding of the naturally balanced ionic microenvironment during bone remodeling can facilitate future biomaterial design for bone tissue engineering in terms of the modulatory roles of the ionic environment in the regenerative process.
Publisher: ACTAPRESS
Date: 2012
Publisher: Wiley
Date: 07-2001
DOI: 10.1902/JOP.2001.72.7.849
Abstract: The plasminogen activator system has been proposed to play a role in proteolytic degradation of extracellular matrices in tissue remodeling, including wound healing. The aim of this study was to elucidate the presence of components of the plasminogen activator system during different stages of periodontal wound healing. Periodontal wounds were created around the molars of adult rats and healing was followed for 28 days. Immunohistochemical analyses of the healing tissues and an analysis of the periodontal wound healing fluid by ELISA were carried out for the detection of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and 2 plasminogen activator inhibitors (PAI-1 and PAI-2). During the early stages (days 1 to 3) of periodontal wound healing, PAI-1 and PAI-2 were found to be closely associated with the deposition of a fibrin clot in the gingival sulcus. These components were strongly associated with the infiltrating inflammatory cells around the fibrin clot. During days 3 to 7, u-PA, PAI-1, and PAI-2 were associated with cells (particularly monocytes/macrophages, fibroblasts, and endothelial cells) in the newly formed granulation tissue. During days 7 to 14, a new attachment apparatus was formed during which PAI-1, PAI-2, and u-PA were localized in both periodontal ligament fibroblasts (PDL) and epithelial cells at sites where these cells were attaching to the root surface. In the periodontal wound healing fluid, the concentration for t-PA increased and peaked during the first week. PAI-2 had a similar expression to t-PA, but at a lower level over the entire wound-healing period. These findings indicate that the plasminogen activator system is involved in the entire process of periodontal wound healing, in particular with the formation of fibrin matrix on the root surface and its replacement by granulation tissue, as well as the subsequent formation of the attachment of soft tissue to the root surface during the later stages of wound repair.
Publisher: Wiley
Date: 08-06-2022
DOI: 10.1111/JRE.13022
Abstract: Growing evidence suggests that excessive inflammation h ers the regenerative capacity of periodontal ligament cells (PDLCs) and that activation of the Wnt/β-catenin pathway is crucial in suppressing immune dysregulation. This study aimed to establish the role of the Wnt/β-catenin in regulating the immune microenvironment and its subsequent impact on periodontal regeneration. Lithium chloride (LiCl, Wnt activator) was administered daily into the standard periodontal defects created in 12-week-old Lewis rats. Harvested at 1-week and 2-week post-surgery, s les were then subjected to histological and immunohistochemical evaluation of macrophage distribution and phenotype (pro-inflammatory M1 and anti-inflammatory M2). A murine macrophage cell line, RAW 264.7, was stimulated with LiCl to activate Wnt/β-catenin. Following treatment with the conditioned medium derived from the LiCl-activated macrophages, the expression of bone- and cementum-related markers of the PDLCs was determined. The involvement of Wnt/β-catenin in the immunoregulation and autophagic activity was further investigated with the addition of cardamonin, a commercially available Wnt inhibitor. A significantly increased number of macrophages were detected around the defects during early healing upon receiving the Wnt/β-catenin signaling cue. The defect sites in week 2 exhibited fewer M1 and more M2 macrophages along with an enhanced regeneration of alveolar bone and cementum in the Wnt/β-catenin activation group. LiCl-induced immunomodulatory effect was accompanied with the activation Wnt/β-catenin signaling, which was suppressed in the presence of Wnt inhibitor. Exposure to LiCl could induce autophagy in a dose-dependent manner, thus maintaining macrophages in a regulatory state. The expression level of bone- and cementum-related markers was significantly elevated in PDLCs stimulated with LiCl-activated macrophages. The application of Wnt activator LiCl facilitates the recruitment of macrophages to defect sites and regulates their phenotypic switching in favor of periodontal regeneration. Suppression of Wnt/β-catenin pathway could attenuate the LiCl-induced immunomodulatory effect. Taken together, the Wnt/β-catenin pathway may be targeted for therapeutic interventions in periodontal diseases.
Publisher: Royal Society of Chemistry (RSC)
Date: 05-06-2014
DOI: 10.1039/C4BM00111G
Publisher: Elsevier BV
Date: 11-2015
Publisher: Frontiers Media SA
Date: 31-01-2022
DOI: 10.3389/FCELL.2021.803132
Abstract: Intervertebral disc degeneration (IDD) is closely associated with low back pain, but its underlying mechanism remains unclear. Cholesterol is an essential nutrient in mammalian cells. Alterations in cholesterol levels lead to impairments in cell physiology, such as cell proliferation and signal transduction. Previous clinical studies demonstrated that hypercholesterolemia could be a potential risk factor for IDD, but how cholesterol induces IDD remains unknown. The current study aimed to explore the regulatory role of cholesterol in IDD development and the potential underlying mechanisms. It was found that different forms of cholesterol levels were elevated in degenerative nucleus pulposus (NP) tissues in both humans and Sprague–Dawley rats. Rats fed a high cholesterol diet (HCD) exhibited degenerative features in the lumbar intervertebral disc compared with those fed a standard diet. Interestingly, this effect could be abolished by cholesterol-lowering drug atorvastatin. In NP cells treated with TNF-α and IL-1β, a significantly higher level of cholesterol was observed. These results suggested a pivotal role of cholesterol in the progression of IDD. We also observed accelerated pyroptosis in NP cells and extracellular matrix (ECM) degradation in the rat NP cells treated with exogenous cholesterol. We further demonstrated that endoplasmic reticulum stress was responsible for cholesterol-induced pyroptosis and ECM degradation. Moreover, RNA-seq analysis revealed that the mature form of SREBP1 (mSREBP1), an important regulator of lipid metabolism, is involved in regulating endoplasmic reticulum stress in knockdown experiments. In conclusion, this study demonstrated that cholesterol could induce pyroptosis in NP cells and ECM degradation by activating endoplasmic reticulum stress through stimulating mSREBP1 in IDD.
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.BIOMATERIALS.2012.04.038
Abstract: This study describes the design of a biphasic scaffold composed of a Fused Deposition Modeling scaffold (bone compartment) and an electrospun membrane (periodontal compartment) for periodontal regeneration. In order to achieve simultaneous alveolar bone and periodontal ligament regeneration a cell-based strategy was carried out by combining osteoblast culture in the bone compartment and placement of multiple periodontal ligament (PDL) cell sheets on the electrospun membrane. In vitro data showed that the osteoblasts formed mineralized matrix in the bone compartment after 21 days in culture and that the PDL cell sheet harvesting did not induce significant cell death. The cell-seeded biphasic scaffolds were placed onto a dentin block and implanted for 8 weeks in an athymic rat subcutaneous model. The scaffolds were analyzed by μCT, immunohistochemistry and histology. In the bone compartment, a more intense ALP staining was obtained following seeding with osteoblasts, confirming the μCT results which showed higher mineralization density for these scaffolds. A thin mineralized cementum-like tissue was deposited on the dentin surface for the scaffolds incorporating the multiple PDL cell sheets, as observed by H&E and Azan staining. These scaffolds also demonstrated better attachment onto the dentin surface compared to no attachment when no cell sheets were used. In addition, immunohistochemistry revealed the presence of CEMP1 protein at the interface with the dentine. These results demonstrated that the combination of multiple PDL cell sheets and a biphasic scaffold allows the simultaneous delivery of the cells necessary for in vivo regeneration of alveolar bone, periodontal ligament and cementum.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.BONE.2019.06.027
Abstract: Mineralization of bone is a dynamic process, involving a complex interplay between cells, secreted macromolecules, signaling pathways, and enzymatic reactions the dysregulation of bone mineralization may lead to serious skeletal disorders, including hypophosphatemic rickets, osteoporosis, and rheumatoid arthritis. Very few studies have reported the role of osteocytes - the most abundant bone cells in the skeletal system and the major orchestrators of bone remodeling in bone mineralization, which is owed to their nature of being deeply embedded in the mineralized bone matrix. The Wnt/β-catenin signaling pathway is actively involved in various life processes including osteogenesis however, the role of Wnt/β-catenin signaling in the terminal mineralization of bone, especially in the regulation of osteocytes, is largely unknown. This research demonstrates that during the terminal mineralization process, the Wnt/β-catenin pathway is downregulated, and when Wnt/β-catenin signaling is activated in osteocytes, dendrite development is suppressed and the expression of dentin matrix protein 1 (DMP1) is inhibited. Aberrant activation of Wnt/β-catenin signaling in osteocytes leads to the spontaneous deposition of extra-large mineralized nodules on the surface of collagen fibrils. The altered mineral crystal structure and decreased bonding force between minerals and the organic matrix indicate the inferior integration of minerals and collagen. In conclusion, Wnt/β-catenin signaling plays a critical role in the terminal differentiation of osteocytes and as such, targeting Wnt/β-catenin signaling in osteocytes may serve as a potential therapeutic approach for the management of bone-related diseases.
Publisher: Trans Tech Publications, Ltd.
Date: 03-2014
DOI: 10.4028/WWW.SCIENTIFIC.NET/JBBTE.19.65
Abstract: Calcium phosphate ceramic scaffolds have been widely investigated for bone tissue engineering due to their excellent biocompatibility and biodegradation. Unfortunately, they have low mechanical properties, which inversely restrict their wide applications in load-bearing bone tissue engineering. In this study, porous Si-doped tri-calcium phosphate (TCP) ceramics with a high porosity (~65%) and with interconnected macrotubes (~0.8mm in diameter) and micropores (5-100 μm) were prepared by firing hydroxyapatite (HA)/ bioactive glass-impregnated acrylontrile butadiene styrene (ABS) templates at 1400 °C. Results indicated that the cylindrical scaffolds had a higher compressive strength than the cubic scaffolds and the smallest cylindrical scaffold had a highest compressive strength (14.68+0.2MPa). Additional studies of cell attachment and MTT cytotoxicity assay proved the bioactivity and biocompatibility of the Si-doped TCP scaffolds.
Publisher: American Chemical Society (ACS)
Date: 30-11-2019
DOI: 10.1021/ACS.NANOLETT.9B04216
Abstract: Microglia-mediated neuroinflammation is one of the most significant features in a variety of central nervous system (CNS) disorders such as traumatic brain injury, stroke, and many neurodegenerative diseases. Microglia become polarized upon stimulation. The two extremes of the polarization are the neuron-destructive proinflammatory M1-like and the neuron-regenerative M2-like phenotypes. Thus, manipulating microglial polarization toward the M2 phenotype is a promising therapeutic approach for CNS repair and regeneration. It has been reported that nanoparticles are potential tools for regulating microglial polarization. Gold nanoclusters (AuNCs) could penetrate the blood-brain barrier and have neuroprotective effects, suggesting the possibility of utilizing AuNCs to regulate microglial polarization and improve neuronal regeneration in CNS. In the current study, AuNCs functionalized with dihydrolipoic acid (DHLA-AuNCs), an antioxidant with demonstrated neuroprotective roles, were prepared, and their effects on polarization of a microglial cell line (BV2) were examined. DHLA-AuNCs effectively suppressed proinflammatory processes in BV2 cells by inducing polarization toward the M2-like phenotype. This was associated with a decrease in reactive oxygen species and reduced NF-kB signaling and an improvement in cell survival coupled with enhanced autophagy and inhibited apoptosis. Conditioned medium from DHLA-AuNC-treated BV2 cells was able to enhance neurogenesis in both the neuronal cell line N2a and in an ex vivo brain slice stroke model. The direct treatment of brain slices with DHLA-AuNCs also ameliorated stroke-related tissue injury and reduced astrocyte activation (astrogliosis). This study suggests that by regulating neuroinflammation to improve neuronal regeneration, DHLA-AuNCs could be a potential therapeutic agent in CNS disorders.
Publisher: MDPI AG
Date: 23-05-2022
DOI: 10.3390/BIOMEDICINES10051203
Abstract: Macrophages are the most important innate immune cells that participate in various inflammation-related diseases. Therefore, macrophage-related pathological processes are essential targets in the diagnosis and treatment of diseases. Since nanoparticles (NPs) can be preferentially taken up by macrophages, NPs have attracted most attention for specific macrophage-targeting. In this review, the interactions between NPs and the immune system are introduced to help understand the pharmacokinetics and biodistribution of NPs in immune cells. The current design and strategy of NPs modification for specific macrophage-targeting are investigated and summarized.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.JOCA.2016.06.005
Abstract: Hypoxia is known to stabilize hypoxia-inducible factor (HIF) and initiate angiogenic signaling cascade. However, cartilage living in hypoxia environment can maintain avascularity. It is well known that abrogation of avascularity is related to cartilage degradation in osteoarthritis (OA). The aims of present study were to investigate the role of chondromodulin-1 (ChM-1), an endogenously anti-angiogenic protein in cartilage, during chondrocyte maturation and OA progression, as well as to explore the molecular mechanisms underlying the function of ChM-1 with a focus on HIF-2α pathway. Angiogenic-related markers were evaluated in OA cartilage and different stages of chondrocyte differentiation. Chondrocytes transfected with ChM-1 lentivirus or siRNA was treated with tumor necrosis factor (TNF-α) to investigate the role of ChM-1 in chondrocyte hypertrophic changes. In vivo study was conducted by using a surgical induced OA rat model with intra-articular injection of lentivirus ChM-1 (LV-ChM-1) or mock lentivirus (LV-GFP) control. Transcriptional activity of HIF-2α was determined by chromatin immunoprecipitation (ChIP) assay to unveil the mechanisms of ChM-1. Majority angiogenic factors increased in severe OA cartilage, while anti-angiogenic factors including ChM-1 decreased. ChM-1 expression was strongly related with chondrocyte differentiation and chondrogenesis in vitro. ChM-1 overexpression protected chondrocytes from TNF-α induced hypertrophy, and intra-articular injection of LV-ChM-1 delayed OA progression. ChM-1 delayed HIF-2α nuclear translocation at early time-points and decreased transcriptional activity of HIF-2α on collagen type Х α1 (COL10A1), vascular endothelial growth factor A (VEGFA) and matrix metallopeptidase-13 (MMP-13). ChM-1 maintains cartilage homeostasis by inhibiting HIF-2α induced catabolic activity and regulation of ChM-1 in cartilage may be a promising therapeutic strategy for OA.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.JOEN.2007.02.009
Abstract: There is an increasing interest in the utility of dental pulp stem cells (DPSCs) for dentin regeneration. The mechanisms involved in DPSC differentiation remain poorly understood. The purpose of the study was to investigate the mineralization capacity of human dental pulp cells (DPCs) and identify potential markers for odontoblast differentiation. The isolated DPCs expressed mesenchymal stem-cell markers as shown by flow cytometry and could differentiate in vitro into odontogenic, adipogenic, and chondrogenic lineages. Alkaline phosphatase activity of DPCs elevated over time, with significant upregulation on day 21 in odontogenic induction. Quantitative RT-PCR revealed that osteocalcin, dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoglycoprotein (MEPE) expression also increased time dependently in the induction cultures. In conclusion, we isolated DPCs with stem cell characteristics. MEPE and DSPP showed a similar regulatory pattern of DPCs mineralization. MEPE along with DSPP may be potential odontogenetic differentiation markers.
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.BIOMATERIALS.2010.01.083
Abstract: The periosteum plays an indispensable role in both bone formation and bone defect healing. In this study we constructed an artificial in vitro periosteum by incorporating osteogenic differentiated bone marrow stromal cells (BMSCs) and cobalt chloride (CoCl(2))-treated BMSCs. The engineered periostea were implanted both subcutaneously and into skull bone defects in SCID mice to investigate ectopic and orthotopic osteogenesis and vascularization. After two weeks in subcutaneous and four weeks in bone defect areas, the implanted constructs were assessed for ectopic and orthotopic osteogenesis and vascularization by micro-CT, histomorphometrical and immunohistochemical methods. The results showed that CoCl(2) pre-treated BMSCs induced higher degree of vascularization and enhanced osteogenesis within the implants in both ectopic and orthotopic areas. This study provided a novel approach using BMSCs sourced from the same patient for both osteogenic and pro-angiogenic purposes in constructing tissue engineered periosteum to enhance vascularized osteogenesis.
Publisher: Mary Ann Liebert Inc
Date: 02-2007
Abstract: Understanding the molecular mechanisms involved in periodontal regeneration is important for the development of more predictable clinical techniques. This study aimed to identify these mechanisms by comparing the gene expression profiles of cells derived from regenerating defects with patient-matched periodontal ligament cells. Gene profiling was carried out via Affymetrix U133A arrays containing probes for 22,000 genes. Robust differences in gene expression were obtained by identifying genes that consistently changed by a minimum of 2-fold. Analysis of molecular function as designated by gene ontology (GO) identified differentially regulated mechanisms including protein metabolism, tyrosine kinase activity, and skeletal development. The differentially expressed genes could be broadly ided into the categories of protein biosynthesis and turnover, structural constituents of the cytoskeleton and extracellular matrix, and signal transduction. The differential expression of 4 genes (EGR-1, elastin, osteoprotegerin, and IGFBP3) was confirmed via real-time polymerase chain reaction (PCR). Further, the expression of another 2 differentially expressed transcripts, decorin and biglycan, was immunohistochemically confirmed in a periodontal wound healing model and the protein expression was consistent with the pattern of gene expression. This study gives insight into the molecular processes involved in periodontal regeneration and identifies cell markers that are characteristic of regenerating periodontal tissues.
Publisher: MDPI AG
Date: 11-04-2022
DOI: 10.3390/IJMS23084212
Abstract: Osteocytes function as the master orchestrator of bone remodeling activity in the telophase of osseointegration. However, most contemporary studies focus on the manipulation of osteoblast and/or osteoclast functionality via implant surface engineering, which neglects the pivotal role of osteocytes in de novo bone formation. It is confirmative that osteocyte processes extend directly to the implant surface, but whether the surface physicochemical properties can affect the functionality of osteocytes and determine the fate of the osseointegration in the final remodeling stage remains to be determined. Titania nanotube arrays (NTAs) with distinct diameters were fabricated to investigate the relationship between the nanoscale topography and the functionality of osteocytes. In vitro results pinpointed that NTA with a diameter of 15 nm (NTA-15) significantly promote osteogenesis of osteocytes via the enhancement of spreading, proliferation, and mineralization. The osteocyte transcriptome of each group further revealed that the TGF-β signaling pathway plays a pivotal role in osteocyte-mediated osteogenesis. The in vivo study definitely mirrored the aforementioned results, that NTA-15 significantly promotes bone formation around the implant. Consequently, nanoscaled topography-induced osteocyte functionality is important in late osseointegration. This suggests that surface designs targeting osteocytes may, therefore, be a potential approach to solving the aseptic loosening of the implant, and thus strengthen osseointegration.
Publisher: Medical Journals Sweden AB
Date: 05-09-2015
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.ACTBIO.2015.11.033
Abstract: The application of mesoporous silica nanospheres (MSNs) loaded with drugs/growth factors to induce osteogenic differentiation of stem cells has been trialed by a number of researchers recently. However, limitations such as high cost, complex fabrication and unintended side effects from supraphysiological concentrations of the drugs/growth factors represent major obstacles to any potential clinical application in the near term. In this study we reported an in situ one-pot synthesis strategy of MSNs doped with hypoxia-inducing copper ions and systematically evaluated the nanospheres by in vitro biological assessments. The Cu-containing mesoporous silica nanospheres (Cu-MSNs) had uniform spherical morphology (∼100nm), ordered mesoporous channels (∼2nm) and homogeneous Cu distribution. Cu-MSNs demonstrated sustained release of both silicon (Si) and Cu ions and controlled degradability. The Cu-MSNs were phagocytized by immune cells and appeared to modulate a favorable immune environment by initiating proper pro-inflammatory cytokines, inducing osteogenic/angiogenic factors and suppressing osteoclastogenic factors by the immune cells. The immune microenvironment induced by the Cu-MSNs led to robust osteogenic differentiation of bone mesenchymal stem cells (BMSCs) via the activation of Oncostation M (OSM) pathway. These results suggest that the novel Cu-MSNs could be used as an immunomodulatory agent with osteostimulatory capacity for bone regeneration/therapy application. In order to stimulate both osteogenesis and angiogenesis of stem cells for further bone regeneration, a new kind of hypoxia-inducing copper doped mesoporous silica nanospheres (Cu-MSNs) were prepared via one-pot synthesis. Biological assessments under immune environment which better reflect the in vivo response revealed that the nanospheres possessed osteostimulatory capacity and had potential as immunomodulatory agent for bone regeneration/therapy application. The strategy of introducing controllable amount of therapeutic ions instead of loading expensive drugs/growth factors in mesoporous silica nanosphere provides new options for bioactive nanomaterial functionalization.
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2BM00108J
Publisher: Mary Ann Liebert Inc
Date: 12-2003
DOI: 10.1089/10763270360728071
Abstract: Regeneration of osseous defects by a tissue-engineering approach provides a novel means of treatment utilizing cell biology, materials science, and molecular biology. In this study the concept of tissue engineering was tested with collagen type I matrices seeded with cells with osteogenic potential and implanted into sites where osseous damage had occurred. Explant cultures of cells from human alveolar bone and gingiva were established. When seeded into a three-dimensional type I collagen-based scaffold, the bone-derived cells maintained their osteoblastic phenotype as monitored by mRNA and protein levels of the bone-related proteins including bone sialoprotein, osteocalcin, osteopontin, bone morphogenetic proteins 2 and 4, and alkaline phosphatase. These in vitro-developed matrices were implanted into critical-size bone defects in skulls of immunodeficient (SCID) mice. Wound healing was monitored for up to 4 weeks. When measured by microdensitometry the bone density within defects filled with osteoblast-derived matrix was significantly higher compared with defects filled with either collagen scaffold alone or collagen scaffold impregnated with gingival fibroblasts. New bone formation was found at all the sites treated with the osteoblast-derived matrix at 28 days, whereas no obvious new bone formation was identified at the same time point in the control groups. In situ hybridization for the human-specific Alu gene sequence indicated that the newly formed bone tissue resulted from both transplanted human osteoblasts and endogenous mesenchymal stem cells. The results indicate that cells derived from human alveolar bone can be incorporated into bioengineered scaffolds and synthesize a matrix, which on implantation can induce new bone formation.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Mary Ann Liebert Inc
Date: 02-2010
Publisher: Springer Science and Business Media LLC
Date: 29-04-2020
DOI: 10.1038/S41368-020-0078-6
Abstract: Efforts to control inflammation and achieve better tissue repair in the treatment of periodontitis have been ongoing for years. Human β-defensin 3, a broad-spectrum antimicrobial peptide has been proven to have a variety of biological functions in periodontitis however, relatively few reports have addressed the effects of human periodontal ligament cells (hPDLCs) on osteogenic differentiation. In this study, we evaluated the osteogenic effects of hPDLCs with an adenoviral vector encoding human β-defensin 3 in an inflammatory microenvironment. Then human β-defensin 3 gene-modified rat periodontal ligament cells were transplanted into rats with experimental periodontitis to observe their effects on periodontal bone repair. We found that the human β-defensin 3 gene-modified hPDLCs presented with high levels of osteogenesis-related gene expression and calcium deposition. Furthermore, the p38 MAPK pathway was activated in this process. In vivo, human β-defensin 3 gene-transfected rat PDLCs promoted bone repair in SD rats with periodontitis, and the p38 mitogen-activated protein kinase (MAPK) pathway might also have been involved. These findings demonstrate that human β-defensin 3 accelerates osteogenesis and that human β-defensin 3 gene modification may offer a potential approach to promote bone repair in patients with periodontitis.
Publisher: Wiley
Date: 19-02-2009
DOI: 10.1002/JCB.22088
Abstract: Mesenchymal stem cells (MSCs) have attracted immense research interest in the field of regenerative medicine due to their ability to be cultured for successive passages and multi-lineage differentiation. The molecular mechanisms governing MSC self-renewal and differentiation remain largely unknown. The development of sophisticated techniques, in particular clinical proteomics, has enabled researchers in various fields to identify and characterize cell specific biomarkers for therapeutic purposes. This study seeks to understand the cellular and sub-cellular processes responsible for the existence of stem cell populations in bone marrow s les by revealing the whole cell proteome of the clonal cultures of bone marrow-derived MSCs (BMSCs). Protein profiling of the MSC clonal populations was conducted by Two-Dimensional Liquid Chromatography/Matrix-Assisted Laser Desorption/Ionisation (MALDI) Mass Spectrometry (MS). A total of 83 proteins were identified with high confidence of which 11 showed differential expression between subpopulations, which included cytoskeletal and structural proteins, calcium binding proteins, cytokinetic proteins, and members of the intermediate filament family. This study generated a proteome reference map of BMSCs from the clonal populations, which will be valuable to better understand the underlying mechanism of BMSC self-renewal and differentiation.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.DIFF.2010.12.003
Abstract: Angiogenesis, or neovascularization, is a finely balanced process controlled by pro- and anti-angiogenic factors. Vascular endothelial growth factor (VEGF) is a major pro-angiogenic factor, whereas pigment epithelial-derived factor (PEDF) is the most potent natural angiogenesis inhibitor. In this study, the regulatory role of bone marrow stromal cells (BMSCs) during angiogenesis was assessed by the endothelial differentiation potential, VEGF/PEDF production and responses to pro-angiogenic and hypoxic conditions. The in vivo regulation of blood vessel formation by BMSCs was also explored in a SCID mouse model. Results showed that PEDF was expressed more prominently in BMSCs compared to VEGF. This contrasted with human umbilical vein endothelial cells (HUVECs) where the expression of VEGF was higher than that of PEDF. The ratio of VEGF/PEDF gene expression in BMSCs increased when VEGF concentration reached 40ng/ml in the culture medium, but decreased at 80ng/ml. Under CoCl(2)-induced hypoxic conditions, the VEGF/PEDF ratio of BMSCs increased significantly in both normal and angiogenic culture media. There was no expression of endothelial cell markers in BMSCs cultured in either pro-angiogenic or hypoxia culture conditions when compared with HUVECs. The in vivo study showed that VEGF/PEDF expression closely correlated with the degree of neovascularization, and that hypoxia significantly induced pro-angiogenic activity in BMSCs. These results indicate that, rather than being progenitors of endothelial cells, BMSCs play an important role in regulating the neovascularization process, and that the ratio of VEGF and PEDF may, in effect, be an indicator of the pro- or anti-angiogenic activities of BMSCs.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.ACTBIO.2013.10.013
Abstract: The nanostructured surface of biomaterials plays an important role in improving their in vitro cellular bioactivity as well as stimulating in vivo tissue regeneration. Inspired by the mussel's adhesive versatility, which is thought to be due to the plaque-substrate interface being rich in 3,4-dihydroxy-l-phenylalamine (DOPA) and lysine amino acids, in this study we developed a self-assembly method to prepare a uniform calcium phosphate (Ca-P) olydopamine composite nanolayer on the surface of β-tricalcium phosphate (β-TCP) bioceramics by soaking β-TCP bioceramics in Tris-dopamine solution. It was found that the addition of dopamine, reaction temperature and reaction time are three key factors inducing the formation of a uniform Ca-P olydopamine composite nanolayer. The formation mechanism of a Ca-P olydopamine composite nanolayer involved two important steps: (i) the addition of dopamine to Tris-HCl solution decreases the pH value and accelerates Ca and P ionic dissolution from the crystal boundaries of β-TCP ceramics (ii) dopamine is polymerized to form self-assembled polydopamine film and, at the same time, nanosized Ca-P particles are mineralized with the assistance of polydopamine, in which the formation of polydopamine occurs simultaneously with Ca-P mineralization (formation of nanosized microparticles composed of calcium phosphate-based materials), and finally a self-assembled Ca-P olydopamine composite nanolayer forms on the surface of the β-TCP ceramics. Furthermore, the formed self-assembled Ca-P olydopamine composite nanolayer significantly enhances the surface roughness and hydrophilicity of β-TCP ceramics, and stimulates the attachment, proliferation, alkaline phosphate (ALP) activity and bone-related gene expression (ALP, OCN, COL1 and Runx2) of human bone marrow stromal cells. Our results suggest that the preparation of self-assembled Ca-P olydopamine composite nanolayers is a viable method to modify the surface of biomaterials by significantly improving their surface physicochemical properties and cellular bioactivity for bone regeneration application.
Publisher: Aging and Disease
Date: 2022
Publisher: MDPI AG
Date: 28-01-2021
Abstract: Altered subchondral bone and articular cartilage interactions have been implicated in the pathogenesis of osteoarthritis (OA) however, the mechanisms remain unknown. Exosomes are membrane-derived vesicles that have recently been recognized as important mediators of intercellular communication. Herein, we investigated if OA subchondral bone derived exosomes alter transcriptional and bioenergetic signatures of chondrocytes. Exosomes were isolated and purified from osteoblasts of nonsclerotic or sclerotic zones of human OA subchondral bone and their role on the articular cartilage chondrocytes was evaluated by measuring the extent of extracellular matrix production, cellular bioenergetics, and the expression of chondrocyte activity associated marker genes. Exosomal microRNAs were analyzed using RNA sequencing and validated by quantitative real-time PCR and loss-of-function. In coculture studies, chondrocytes internalized OA sclerotic subchondral bone osteoblast derived exosomes and triggered catabolic gene expression and reduced chondrocyte-specific marker expression a phenomenon that is often observed in OA cartilage. RNA sequencing and miRNA profiling have identified miR-210-5p, which is highly enriched in OA sclerotic subchondral bone osteoblast exosomes, triggered the catabolic gene expression in articular cartilage chondrocytes. Importantly, we demonstrate that miR-210-5p suppresses the oxygen consumption rate of chondrocytes, altering their bioenergetic state that is often observed in OA conditions. These effects were markedly inhibited by the addition of a miR-210-5p inhibitor. Our study indicates that exosomes released by OA sclerotic subchondral bone osteoblasts plays a critical role in progression of cartilage degeneration and might be a potential target for therapeutic intervention in OA.
Publisher: CRC Press
Date: 29-04-2003
Publisher: American Chemical Society (ACS)
Date: 04-09-2021
DOI: 10.1021/BM401139E
Abstract: An influenza virus-inspired polymer mimic nanocarrier was used to deliver siRNA for specific and near complete gene knockdown of an osteoscarcom cell line (U-2SO). The polymer was synthesized by single-electron transfer living radical polymerization (SET-LRP) at room temperature to avoid complexities of transfer to monomer or polymer. It was the only LRP method that allowed good block copolymer formation with a narrow molecular weight distribution. At nitrogen to phosphorus (N/P) ratios of equal to or greater than 20 (greater than a polymer concentration of 13.8 μg/mL) with polo-like kinase 1 (PLK1) siRNA gave specific and near complete (>98%) cell death. The polymer further degrades to a benign polymer that showed no toxicity even at polymer concentrations of 200 μg/mL (or N/P ratio of 300), suggesting that our polymer nanocarrier can be used as a very effective siRNA delivery system and in a multiple dose administration. This work demonstrates that with a well-designed delivery device, siRNA can specifically kill cells without the inclusion of an additional clinically used highly toxic cochemotherapeutic agent. Our work also showed that this excellent delivery is sensitive for the study of off-target knockdown of siRNA.
Publisher: Mary Ann Liebert Inc
Date: 05-2015
Publisher: Wiley
Date: 21-01-2009
DOI: 10.1111/J.1600-0501.2008.01630.X
Abstract: Osteoporosis is known to impair the process of implant osseointegration. The recent discovery that statins (HMG-CoA reductase inhibitors) act as bone anabolic agents suggests that statins can be used as potential agents in the treatment of osteoporosis. Therefore, we hypothesized that statins will promote osteogenesis around titanium implants in subjects with osteoporosis. Fifty-four female Sprague Dawley rats, aged 3 months old, were randomly ided into three groups: Sham-operated group (SHAM n=18), ovariectomized group (OVX n=18), and ovariectomized with Simvastatin treatment group (OVX+SIM n=18). Fifty-six days after being ovariectomized (OVX), screw-shaped titanium implants were inserted into the tibiae. Simvastatin was administered orally at 5 mg/kg each day after the placement of the implant in the OVX+SIM group. The animals were sacrificed at either 28 or 84 days after implantation and the undecalcified tissue sections were obtained. Bone-to-implant contact (BIC) and bone area (BA) within the limits of implant threads were measured around the cortical (zone A) and cancellous (zone B) bone regions. Furthermore, bone density (BD) of zone B in a 500 microm wide zone lateral to the implants was also measured. There were no significant differences in BIC and BA measurements in zone A in any of the three groups at either 28 or 84 days after implantation (P>0.05). By contrast, in zone B, significant differences in the measurement of BIC, BA, and BD were observed at 28 and 84 days between all three groups. Bone healing decreased with lower BIC, BA, and BD around implant in OVX group compared with other two groups, and Simvastatin reversed the negative effect of OVX on bone healing around implants with the improvement of BIC, BA, and BD in zone B. Osteoporosis can significantly influence bone healing in the cancellous bone around titanium implants and Simvastatin was shown to significantly improve the osseointegration of pure titanium implants in osteoporotic rats.
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.ACTBIO.2010.12.019
Abstract: Mesoporous bioactive glass (MBG) is a new class of biomaterials with a well-ordered nanochannel structure, whose in vitro bioactivity is far superior than that of non-mesoporous bioactive glass (BG) the material's in vivo osteogenic properties are, however, yet to be assessed. Porous silk scaffolds have been used for bone tissue engineering, but this material's osteoconductivity is far from optimal. The aims of this study were to incorporate MBG into silk scaffolds in order to improve their osteoconductivity and then to compare the effect of MBG and BG on the in vivo osteogenesis of silk scaffolds. MBG/silk and BG/silk scaffolds with a highly porous structure were prepared by a freeze-drying method. The mechanical strength, in vitro apatite mineralization, silicon ion release and pH stability of the composite scaffolds were assessed. The scaffolds were implanted into calvarial defects in SCID mice and the degree of in vivo osteogenesis was evaluated by microcomputed tomography (μCT), hematoxylin and eosin (H&E) and immunohistochemistry (type I collagen) analyses. The results showed that MBG/silk scaffolds have better physiochemical properties (mechanical strength, in vitro apatite mineralization, Si ion release and pH stability) compared to BG/silk scaffolds. MBG and BG both improved the in vivo osteogenesis of silk scaffolds. μCT and H&E analyses showed that MBG/silk scaffolds induced a slightly higher rate of new bone formation in the defects than did BG/silk scaffolds and immunohistochemical analysis showed greater synthesis of type I collagen in MBG/silk scaffolds compared to BG/silk scaffolds.
Publisher: Wiley
Date: 21-04-2014
DOI: 10.1111/CLR.12178
Abstract: Titanium implant surfaces with modified topographies have improved osteogenic properties in vivo. However, the molecular mechanisms remain obscure. This study explored the signaling pathways responsible for the pro-osteogenic properties of micro-roughened (SLA) and chemically/nanostructurally (modSLA) modified titanium surfaces on human alveolar bone-derived osteoprogenitor cells (BCs) in vitro. The activation of stem cell signaling pathways (TGFβ/BMP, Wnt, FGF, Hedgehog, Notch) was investigated following early exposure (24 and 72 h) of BCs to SLA and modSLA surfaces in the absence of osteogenic cell culture supplements. Key regulatory genes from the TGFβ/BMP (TGFBR2, BMPR2, BMPR1B, ACVR1B, SMAD1, SMAD5), Wnt (Wnt/β-catenin and Wnt/Ca(2+) ) (FZD1, FZD3, FZD5, LRP5, NFATC1, NFATC2, NFATC4, PYGO2, LEF1) and Notch (NOTCH1, NOTCH2, NOTCH4, PSEN1, PSEN2, PSENEN) pathways were upregulated on the modified surfaces. These findings correlated with a higher expression of osteogenic markers bone sialoprotein (IBSP) and osteocalcin (BGLAP), and bone differentiation factors BMP2, BMP6, and GDF15, as observed on the modified surfaces. These findings demonstrate that the activation of the pro-osteogenic cell signaling pathways by modSLA and SLA surfaces leads to enhanced osteogenic differentiation as evidenced after 7 and 14 days culture in osteogenic media and provides a mechanistic insight into the superior osseointegration on the modified surfaces observed in vivo.
Publisher: American Chemical Society (ACS)
Date: 29-04-2016
Abstract: Bone tissue engineering offers a possible strategy for regenerating large bone defects, in which how to design beneficial scaffolds for accelerating bone formation remains significantly challenging. Europium, as an important rare earth element, has been used as a solid-state lighting material. However, there are few reports on whether Eu can be used for labeling bone tissue engineering scaffolds, and its biological effect on bone cells and bone tissue regeneration is unknown. In this study, we incorporated Eu into mesoporous bioactive glass (Eu-MBG) scaffolds by an in situ cotemplate method to achieve a bifunctional biomaterial with biolabeling and bone regeneration. The prepared Eu-MBG scaffolds have highly interconnective large pores (300-500 μm), a high specific surface area (140-290 m(2)/g), and well-ordered mesopores (5 nm) as well as uniformly distributed Eu. The incorporation of 2-5 mol % Eu into MBG scaffolds gives them a luminescent property. The in vitro degradation of Eu-MBG scaffolds has a functional effect on the change of the luminescence intensity. In addition, Eu-MBG can be used for labeling bone marrow stromal cells (BMSCs) in vitro and still presents a distinct luminescence signal in deep bone tissues in vivo to label new bone tissue via release of Eu ions. Furthermore, the incorporation of different contents of Eu (1, 2, and 5 mol %) into MBG scaffolds significantly enhances the osteogenic gene expression of BMSCs in the scaffolds. The Eu- and Si-containing ionic products released from Eu-MBG scaffolds distinctly promote the osteogenic differentiation of BMSCs. Critically sized femur defects in ovariectomized (OVX) rats are created to simulate an osteoporotic phenotype. The results show that Eu-MBG scaffolds significantly stimulate new bone formation in osteoporotic bone defects when compared to MBG scaffolds alone and Eu may be involved in the acceleration of bone regeneration in OVX rats. Our study for the first time reports that the incorporation of the rare earth element Eu into bioscaffolds has the ability to accelerate bone regeneration in vivo, and thus, the prepared Eu-MBG scaffolds possess bifunctional properties with biolabeling and bone regeneration.
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.ACTBIO.2010.12.018
Abstract: For a biomaterial to be considered suitable for bone repair it should ideally be both bioactive and have a capacity for controllable drug delivery as such, mesoporous SiO(2) glass has been proposed as a new class of bone regeneration material by virtue of its high drug-loading ability and generally good biocompatibility. It does, however, have less than optimum bioactivity and controllable drug delivery properties. In this study, we incorporated strontium (Sr) into mesoporous SiO(2) in an effort to develop a bioactive mesoporous SrO-SiO(2) (Sr-Si) glass with the capacity to deliver Sr(2+) ions, as well as a drug, at a controlled rate, thereby producing a material better suited for bone repair. The effects of Sr(2+) on the structure, physiochemistry, drug delivery and biological properties of mesoporous Sr-Si glass were investigated. The prepared mesoporous Sr-Si glass was found to have an excellent release profile of bioactive Sr(2+) ions and dexamethasone, and the incorporation of Sr(2+) improved structural properties, such as mesopore size, pore volume and specific surface area, as well as rate of dissolution and protein adsorption. The mesoporous Sr-Si glass had no cytotoxic effects and its release of Sr(2+) and SiO(4)(4-) ions enhanced alkaline phosphatase activity - a marker of osteogenic cell differentiation - in human bone mesenchymal stem cells. Mesoporous Sr-Si glasses can be prepared to porous scaffolds which show a more sustained drug release. This study suggests that incorporating Sr(2+) into mesoporous SiO(2) glass produces a material with a more optimal drug delivery profile coupled with improved bioactivity, making it an excellent material for bone repair applications.
Publisher: American Chemical Society (ACS)
Date: 21-04-2017
Abstract: Osteoimmunomodulation has informed the importance of modulating a favorable osteoimmune environment for successful materials-mediated bone regeneration. Nanotopography is regarded as a valuable strategy for developing advanced bone materials, due to its positive effects on enhancing osteogenic differentiation. In addition to this direct effect on osteoblastic lineage cells, nanotopography also plays a vital role in regulating immune responses, which makes it possible to utilize its immunomodulatory properties to create a favorable osteoimmune environment. Therefore, the aim of this study was to advance the applications of nanotopography with respect to its osteoimmunomodulatory properties, aiming to shed further light on this field. We found that tuning the surface chemistry (amine or acrylic acid) and scale of the nanotopography (16, 38, and 68 nm) significantly modulated the osteoimmune environment, including changes in the expression of inflammatory cytokines, osteoclastic activities, and osteogenic, angiogenic, and fibrogenic factors. The generated osteoimmune environment significantly affected the osteogenic differentiation of bone marrow stromal cells, with carboxyl acid-tailored 68 nm surface nanotopography offering the most promising outcome. This study demonstrated that the osteoimmunomodulation could be manipulated via tuning the chemistry and nanotopography, which implied a valuable strategy to apply a "nanoengineered surface" for the development of advanced bone biomaterials with favorable osteoimmunomodulatory properties.
Publisher: Wiley
Date: 30-09-2014
DOI: 10.1002/JBM.A.34954
Abstract: Osteocytes, known to act as the main regulators of bone homeostasis, have become a major focus in the field of bone research. Bioactive ceramics have been widely used for bone regeneration. However, there are few studies about the interaction of osteocytes with bioceramics. The effects of osteocytes on the in vitro and in vivo osteogenesis of bioceramics are also unclear. The aim of this study was to investigate the role of osteocytes on the β-tricalcium phosphate (β-TCP) stimulated osteogenesis. It was found that osteocytes responded to the β-TCP stimulation, leading to the release of Wnt (wingless-related MMTV integration site), which enhanced osteogenic differentiation of bone marrow stromal cells via Wnt signaling pathway. Receptor activator of nuclear factor kappa B ligand, an osteoclast inducer, was also upregulated, indicating that osteocytes would also participated in activation of osteoclasts, which played a major role in the degradation process of β-TCP and new bone remodeling. In vivo studies further demonstrated that when the material was completely embedded by newly formed bone, the only cell contacting with the material was osteocyte. However, the material would eventually be degraded and replaced by the new bone, requiring the participation of osteoclasts and osteoblasts, which were demonstrated by using immunostaining in this study. As the only cell contacting with the material, osteocytes probably acted in a regulatory role to regulate the surrounding osteoclasts and osteoblasts. Osteocytes were also found to participate in the maturation of osteoblasts and the mineralization process of biomaterials, by upregulating E11 (podoplanin) and dentin matrix protein 1 expression. These findings indicated that osteocytes involved in bone biomaterial-mediated osteogenesis and biomaterial degradation, providing valuable insights into the mechanism of material-stimulated osteogenesis, and a novel strategy to optimize the evaluating system for the biological properties of biomaterials.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 2019
DOI: 10.2139/SSRN.3368394
Publisher: Humana Press
Date: 2013
DOI: 10.1007/7651_2013_30
Abstract: Mesenchymal stem cells (MSCs) represent multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage cells), and adipocytes (fat cells). Their multi-potency provides a great promise as a cell source for tissue engineering and cell-based therapy for many diseases, particularly bone diseases and bone formation. To be able to direct and modulate the differentiation of MSCs into the desired cell types in situ in the tissue, nanotechnology is introduced and used to facilitate or promote cell growth and differentiation. These nano-materials can provide a fine structure and tuneable surface in nanoscales to help the cell adhesion and promote the cell growth and differentiation of MSCs. This could be a dominant direction in future for stem cells based therapy or tissue engineering for various diseases. Therefore, the isolation, manipulation, and differentiation of MSCs are very important steps to make meaningful use of MSCs for disease treatments. In this chapter, we have described a method of isolating MSC from human bone marrow, and how to culture and differentiate them in vitro. We have also provided research methods on how to use MSCs in an in vitro model and how to observe MSC biological response on the surface of nano-scaled materials.
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.BIOMATERIALS.2009.12.049
Abstract: The rationale for the present study was to develop porous CaP/silk composite scaffolds with a CaP-phase distribution and pore architecture better suited to facilitate osteogenic properties of human bone mesenchymal stromal cells (BMSCs) and in vivo bone formation abilities. This was achieved by first preparing CaP/silk hybrid powders which were then incorporated into silk to obtain uniform CaP/silk composite scaffolds, by means of a freeze-drying method. The composition, microstructure and mechanical properties of the CaP/silk composite scaffolds were ascertained by X-ray diffraction (XRD), Fourier transform infrared spectra (FTIR), scanning electron microscope (SEM) and a universal mechanical testing machine. BMSCs were cultured in these scaffolds and cell proliferation analyzed by confocal microscopy and MTS assay. Alkaline phosphatase (ALP) activity and osteogenic gene expression were assayed to determine if osteogenic differentiation had taken place. A calvarial defect model in SCID mice was used to determine the in vivo bone forming ability of the hybrid CaP/silk scaffolds. Our results showed that incorporating the hybrid CaP/silk powders into silk scaffolds improved both pore structure architecture and distribution of CaP powders in the composite scaffolds. By incorporating the CaP phase into silk scaffolds in vitro osteogenic differentiation of BMSCs was enhanced and there was increased in vivo cancellous bone formation. Here we report a method with which to prepare Ca/P composite scaffolds with a pore structure and Ca/P distribution better suited to facilitate BMSC differentiation and bone formation.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.ACTBIO.2013.06.026
Abstract: Development of hypoxia-mimicking bone tissue engineering scaffolds is of great importance in stimulating angiogenesis for bone regeneration. Dimethyloxallyl glycine (DMOG) is a cell-permeable, competitive inhibitor of hypoxia-inducible factor prolyl hydroxylase (HIF-PH), which can stabilize hypoxia-inducible factor 1α (HIF-1α) expression. The aim of this study was to develop hypoxia-mimicking scaffolds by delivering DMOG in mesoporous bioactive glass (MBG) scaffolds and to investigate whether the delivery of DMOG could induce a hypoxic microenvironment for human bone marrow stromal cells (hBMSC). MBG scaffolds with varied mesoporous structures (e.g. surface area and mesopore volume) were prepared by controlling the contents of mesopore-template agent. The composition, large-pore microstructure and mesoporous properties of MBG scaffolds were characterized. The effect of mesoporous properties on the loading and release of DMOG in MBG scaffolds was investigated. The effects of DMOG delivery on the cell morphology, cell viability, HIF-1α stabilization, vascular endothelial growth factor (VEGF) secretion and bone-related gene expression (alkaline phosphatase, ALP osteocalcin, OCN and osteopontin, OPN) of hBMSC in MBG scaffolds were systematically investigated. The results showed that the loading and release of DMOG in MBG scaffolds can be efficiently controlled by regulating their mesoporous properties via the addition of different contents of mesopore-template agent. DMOG delivery in MBG scaffolds had no cytotoxic effect on the viability of hBMSC. DMOG delivery significantly induced HIF-1α stabilization, VEGF secretion and bone-related gene expression of hBMSC in MBG scaffolds in which DMOG counteracted the effect of HIF-PH and stabilized HIF-1α expression under normoxic condition. Furthermore, it was found that MBG scaffolds with slow DMOG release significantly enhanced the expression of bone-related genes more than those with instant DMOG release. The results suggest that the controllable delivery of DMOG in MBG scaffolds can mimic a hypoxic microenvironment, which not only improves the angiogenic capacity of hBMSC, but also enhances their osteogenic differentiation.
Publisher: American Chemical Society (ACS)
Date: 06-01-2023
Publisher: Elsevier BV
Date: 10-2022
Publisher: Quintessence Publishing
Date: 07-2019
DOI: 10.11607/JOMI.6814
Abstract: It remains unclear whether estrogen deficiency affects the ultrastructure and tissue-level mechanical properties of the maxilla. The hypothesis of this study was that the ovariectomized rat could induce tissue-level changes of the maxilla. Twelve 3-month-old female Sprague Dawley rats were acquired and randomly ided into two groups: ovariectomized and SHAM (control) (n = 6 for each group). Three months after the ovariectomy, implants were placed the animals were sacrificed at day 28, and then s les were collected and prepared according to the previously established protocols. Advanced analytical equipment including scanning electron microscope with energy-dispersive spectrometry, transmission electron microscope, and nanoindentation were used to analyze bone quality. The results showed that the mature bone areas in the ovariectomized group were significantly affected in the mineral crystal and the microstructure. The micro-mechanical properties of the mature bone were also affected, showing significantly increased hardness (H) and reduced modulus (E Ovariectomy affected maxilla bone tissue-level quality however, the effects mainly existed in the mature bone areas, which were characterized by higher crystalline mineralization, hardness, and modulus.
Publisher: Springer Science and Business Media LLC
Date: 17-02-2018
DOI: 10.1007/S00109-018-1625-X
Abstract: Notch is actively involved in various life processes including osteogenesis however, the role of Notch signalling in the terminal mineralisation of bone is largely unknown. In this study, it was noted that Hey1, a downstream target of Notch signalling was highly expressed in mature osteocytes compared to osteoblasts, indicating a potential role of Notch in osteocytes. Using a recently developed thermosensitive cell line (IDG-SW3), we demonstrated that dentin matrix acidic phosphoprotein 1 (DMP1) expression was inhibited and mineralisation process was significantly altered when Notch pathway was inactivated via administration of N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of Notch. Dysregulation of Notch in osteocyte differentiation can result in spontaneous deposition of calcium phosphate on collagen fibrils, disturbed transportation of intracellular mineral vesicles, alteration of mineral crystal structure, decreased bonding force between minerals and organic matrix, and suppression of dendrite development coupled with decreased expression of E11. In conclusion, the evidence presented here suggests that Notch plays a critical role in osteocyte differentiation and biomineralisation process. Notch plays a regulatory role in osteocyte phenotype. Notch modulates the mineralisation mediated by osteocytes. Notch activity influences the ultrastructural properties of bone mineralisation.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Trans Tech Publications Ltd.
Date: 09-02-2008
Publisher: Wiley
Date: 11-06-2004
Publisher: Wiley
Date: 29-04-2010
DOI: 10.1002/ART.27397
Abstract: Previous studies have shown the influence of subchondral bone osteoblasts (SBOs) on phenotypical changes of articular cartilage chondrocytes (ACCs) during the development of osteoarthritis (OA). The molecular mechanisms involved during this process remain elusive, in particular, the signal transduction pathways. The aim of this study was to investigate the in vitro effects of OA SBOs on the phenotypical changes in normal ACCs and to unveil the potential involvement of MAPK signaling pathways during this process. Normal and arthritic cartilage and bone s les were collected for isolation of ACCs and SBOs. Direct and indirect coculture models were applied to study chondrocyte hypertrophy under the influence of OA SBOs. MAPKs in the regulation of the cell-cell interactions were monitored by phosphorylated antibodies and relevant inhibitors. OA SBOs led to increased hypertrophic gene expression and matrix calcification in ACCs by means of both direct and indirect cell-cell interactions. In this study, we demonstrated for the first time that OA SBOs suppressed p38 phosphorylation and induced ERK-1/2 signal phosphorylation in cocultured ACCs. The ERK-1/2 pathway inhibitor PD98059 significantly attenuated the hypertrophic changes induced by conditioned medium from OA SBOs, and the p38 inhibitor SB203580 resulted in the up-regulation of hypertrophic genes in ACCs. The findings of this study suggest that the pathologic interaction of OA SBOs and ACCs is mediated via the activation of ERK-1/2 phosphorylation and deactivation of p38 phosphorylation, resulting in hypertrophic differentiation of ACCs.
Publisher: SAGE Publications
Date: 10-07-2013
Abstract: In this article, we, for the first time, investigated mesoporous bioactive glass scaffolds for the delivery of vascular endothelial growth factor. We have found that mesoporous bioactive glass scaffolds have significantly higher loading efficiency and more sustained release of vascular endothelial growth factor than non-mesoporous bioactive glass scaffolds. In addition, vascular endothelial growth factor delivery from mesoporous bioactive glass scaffolds has improved the viability of endothelial cells. The study has suggested that mesopore structures in mesoporous bioactive glass scaffolds play an important role in improving the loading efficiency, decreasing the burst release, and maintaining the bioactivity of vascular endothelial growth factor, indicating that mesoporous bioactive glass scaffolds are an excellent carrier of vascular endothelial growth factor for potential bone tissue engineering applications.
Publisher: Wiley
Date: 21-07-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9TB01261C
Abstract: Organic phosphate could initiate a selective and hierarchal tissue mineralization in the periodontal complex.
Publisher: Springer Berlin Heidelberg
Date: 2013
DOI: 10.1007/10_2012_143
Abstract: Mesenchymal stem cells (MSCs) are undifferentiated, multi-potent stem cells with the ability to renew. They can differentiate into many types of terminal cells, such as osteoblasts, chondrocytes, adipocytes, myocytes, and neurons. These cells have been applied in tissue engineering as the main cell type to regenerate new tissues. However, a number of issues remain concerning the use of MSCs, such as cell surface markers, the determining factors responsible for their differentiation to terminal cells, and the mechanisms whereby growth factors stimulate MSCs. In this chapter, we will discuss how proteomic techniques have contributed to our current knowledge and how they can be used to address issues currently facing MSC research. The application of proteomics has led to the identification of a special pattern of cell surface protein expression of MSCs. The technique has also contributed to the study of a regulatory network of MSC differentiation to terminal differentiated cells, including osteocytes, chondrocytes, adipocytes, neurons, cardiomyocytes, hepatocytes, and pancreatic islet cells. It has also helped elucidate mechanisms for growth factor-stimulated differentiation of MSCs. Proteomics can, however, not reveal the accurate role of a special pathway and must therefore be combined with other approaches for this purpose. A new generation of proteomic techniques have recently been developed, which will enable a more comprehensive study of MSCs.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4TB00377B
Abstract: Periodontal disease is characterized by the destruction of the tissues that attach the tooth to the alveolar bone.
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.JOEN.2014.10.010
Abstract: Sphingosine-1-phosphate receptor 1 (S1P1) is crucial for regulation of immunity and bone metabolism. This study aimed to investigate the expression of S1P1 in rat periapical lesions and its relationship with receptor activator of nuclear factor kappa B ligand (RANKL) and regulatory T (Treg) cells. Periapical lesions were induced by pulp exposure in the first lower molars of 55 Wistar rats. Thirty rats were killed on days 0, 7, 14, 21, 28, and 35, and their mandibles were harvested for x-ray imaging, micro-computed tomography scanning, histologic observation, immunohistochemistry, enzyme histochemistry, and double immunofluorescence analysis. The remaining 25 rats were killed on days 0, 14, 21, 28, and 35, and mandibles were harvested for flow cytometry. The volume and area of the periapical lesions increased from day 0 to day 21 and then remained comparably stable after day 28. S1P1-positive cells were observed in the inflammatory periapical regions the number of S1P1-positive cells peaked at day 14 and then decreased from day 21 to day 35. The distribution of S1P1-positive cells was positively correlated with the dynamics of RANKL-positive cells but was negatively correlated with that of Treg cells. S1P1 expression was differentially correlated with RANKL and Treg cell infiltration in the periapical lesions and is therefore a contributing factor to the pathogenesis of such lesions.
Publisher: American Chemical Society (ACS)
Date: 14-03-2014
DOI: 10.1021/AM4060035
Abstract: Ideal coating materials for implants should be able to induce excellent osseointegration, which requires several important parameters, such as good bonding strength, limited inflammatory reaction, and balanced osteoclastogenesis and osteogenesis, to gain well-functioning coated implants with long-term life span after implantation. Bioactive elements, like Sr, Mg, and Si, have been found to play important roles in regulating the biological responses. It is of great interest to combine bioactive elements for developing bioactive coatings on Ti-6Al-4 V orthopedic implants to elicit multidirectional effects on the osseointegration. In this study, Sr-, Mg-, and Si-containing bioactive Sr2MgSi2O7 (SMS) ceramic coatings on Ti-6Al-4 V were successfully prepared by the plasma-spray coating method. The prepared SMS coatings have significantly higher bonding strength (∼37 MPa) than conventional pure hydroxyapatite (HA) coatings (mostly in the range of 15-25 MPa). It was also found that the prepared SMS coatings switch the macrophage phenotype into M2 extreme, inhibiting the inflammatory reaction via the inhibition of Wnt5A/Ca(2+) and Toll-like receptor (TLR) pathways of macrophages. In addition, the osteoclastic activities were also inhibited by SMS coatings. The expression of osteoclastogenesis-related genes (RANKL and MCSF) in bone-marrow-derived mesenchymal cells (BMSCs) with the involvement of macrophages was decreased, whereas OPG expression was enhanced on SMS coatings compared to HA coatings, indicating that SMS coatings also downregulated the osteoclastogenesis. However, the osteogenic differentiation of BMSCs with the involvement of macrophages was comparable between SMS and HA coatings. Therefore, the prepared SMS coatings showed multidirectional effects, such as improving bonding strength, reducing inflammatory reaction, and downregulating osteoclastic activities, but maintaining a comparable osteogenesis, as compared with HA coatings. The combination of bioactive elements of Sr, Mg, and Si into bioceramic coatings can be a promising method to develop bioactive implants with multifunctional properties for orthopedic application.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0NR07622H
Abstract: Exosome encapsulation protects and delivers AAV vectors for gene therapy.
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.BIOMATERIALS.2010.01.061
Abstract: Porous mesopore-bioglass (MBG) scaffolds have been proposed as a new class of bone regeneration materials due to their apatite-formation and drug-delivery properties however, the material's inherent brittleness and high degradation and surface instability are major disadvantages, which compromise its mechanical strength and cytocompatibility as a biological scaffold. Silk, on the other hand, is a native biomaterial and is well characterized with respect to biocompatibility and tensile strength. In this study we set out to investigate what effects blending silk with MBG had on the physiochemical, drug-delivery and biological properties of MBG scaffolds with a view to bone tissue engineering applications. Transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were the methods used to analyze the inner microstructure, pore size and morphology, and composition of MBG scaffolds, before and after addition of silk. The effect of silk modification on the mechanical property of MBG scaffolds was determined by testing the compressive strength of the scaffolds and also compressive strength after degradation over time. The drug-delivery potential was evaluated by the release of dexamethasone (DEX) from the scaffolds. Finally, the cytocompatibility of silk-modified scaffolds was investigated by the attachment, morphology, proliferation, differentiation and bone-relative gene expression of bone marrow stromal cells (BMSCs). The results showed that silk modification improved the uniformity and continuity of pore network of MBG scaffolds, and maintained high porosity (94%) and large-pore size (200-400 microm). There was a significant improvement in mechanical strength, mechanical stability, and control of burst release of DEX in silk-modified MBG scaffolds. Silk modification also appeared to provide a better environment for BMSC attachment, spreading, proliferation, and osteogenic differentiation on MBG scaffolds.
Publisher: Mary Ann Liebert Inc
Date: 04-2007
Abstract: The demand for treatment strategies for damaged musculoskeletal tissue is continuously growing, especially with the increasing number of older people with degenerative diseases of the skeletal system such as osteoarthritis (OA). Because depletion of multipotent cells has been implicated in degenerative joint diseases, cell-based therapies have been proposed for tissue regeneration, especially for cartilage repair. The aim of the present study is to focus on the possibility of deriving and expanding multipotential mesenchymal stem cells (MSCs) from bone marrow s les of patients with OA by characterizing MSCs at the single cell level. Single-cell clonal cultures were established in 96-well plates by limiting dilution of bone marrow stromal cells (BMSCs) from three patients with OA. Fourteen clones were established for subsequent characterization. There was a wide variation in cell doubling times, with the time taken to reach 20 population doublings ranging from 37 days to more than 100 days. The clones were grouped into fast-growing and slow-growing clones. All except one of the fast-growing stem cell clones were tripotential. However, the slow-growing clones showed limited differentiation potential and morphological changes associated with cellular senescence with extended duration in culture. Flow cytometric analysis indicated a strong need to investigate for novel cell-surface characteristic markers of BMSCs because there was no obvious difference in the expression of the selected characteristic BMSC cell surface markers CD29, CD44, CD90, CD105, and CD166 between fast-growing and slow-growing clones. This study has demonstrated the existence of a fast-growing multipotential MSC population from bone marrow s les of patients with OA. Therefore, despite a supposedly smaller stem cell compartment in these patients, we demonstrate here that they can still yield a potentially therapeutically useful source of syngeneic MSCs.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.ACTBIO.2019.06.058
Abstract: Developing "osteoimmune-smart" bone substitute materials have become the forefront of research in bone regeneration. Biocompatible polymer coatings are applied widely to improve the bioactivity of bone substitute materials. In this context, polyoxazolines (Pox) have attracted substantial attention recently due to properties such as biocompatibility, stability, and low biofouling. In view of these useful properties, it is interesting to explore the capacity of Pox as an osteoimmunomodulatory agent to generate a favorable osteoimmune environment for osteogenesis. We applied a technique called plasma polymerization and succeeded in preparing Pox-like coatings (Ppox) and engineered their nanotopography at the nanoscale. We found that Ppox switched macrophages towards M2 extreme, thus inhibiting the release of inflammatory cytokines. The underlying mechanism may be related to the suppression of TLR pathway. The generated osteoimmune environment improved osteogenesis while inhibited osteoclastogenesis. This may be related to the release of osteogenic factors, especially Wnt10b from macrophages. The addition of nanotopography (16 nm, 38 nm, 68 nm) can tune the Ppox-mediated inhibition on inflammation and osteoclastic activities, while no significant effects were observed within the tested nano sizes on the Ppox-mediated osteogenesis. These results collectively suggest that Ppox can be useful as an effective osteoiumunomodulatory agent to endow bone substitute materials with favourable osteoimmunomodulatory property. STATEMENT OF SIGNIFICANCE: In this study, we succeeded in preparing plasma deposited Pox-like nano-coatings (Ppox) via plasma polymerization and found that Ppox nanotopographies are useful osteoimmunomodulatory tools. Their osteoimmunodolatory effects and underlying mechanisms are unveiled. It is the first investigation into the feasibility of applying poly-oxazoline as an osteoimmunomodulatory agent. This expand the application of poly-oxazoline into the forefront in bone regeneration area for the development of advanced "osteoimmune-smart" bone substitute materials.
Publisher: Elsevier BV
Date: 09-2019
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.ACTBIO.2019.06.057
Abstract: Biomaterial implantation triggers inflammatory reactions. Understanding the effect of physicochemical features of biomaterials on the release of inflammatory cytokines from immune cells would be of great interest in view of designing bone graft materials to enhance the healing of bone defects. The present work investigated the interactions of two chemically and texturally different calcium phosphate (CaPs) substrates with macrophages, one of the main innate immune cells, and its further impact on osteogenic differentiation of bone forming cells. The behaviour of macrophages seeded on biomimetic calcium deficient hydroxyapatite (CDHA) and sintered β-tricalcium phosphate (β-TCP) was assessed in terms of the release of inflammatory cytokines and osteoclastogenic factors. The osteogenic differentiation of bone progenitor cells (bone marrow stromal cells (BMSCs) and osteoblastic cell line (SaOS-2)) were subsequently studied by incubating with the conditioned medium induced by macrophage-CaPs interaction in order to reveal the effect of immune cell reaction to CaPs on osteogenic differentiation. It was found that the incubation of macrophages with CaPs substrates caused a decrease of pro-inflammatory cytokines, more pronounced for β-TCP compared with CDHA showing significantly decreased IL-6, TNF-a, and iNOS. However, the macrophage-CDHA interaction resulted in a more favourable environment for osteogenic differentiation of osteoblasts with more collagen type I production and osteogenic genes (Runx2, BSP) expression, suggesting that osteogenic differentiation of bone cells is not only determined by the nature of biomaterials, but also significantly influenced by the inflammatory environment generated by the interaction of immune cells and biomaterials. STATEMENT OF SIGNIFICANCE: The field of osteoimmunology highlights the importance of the cross-talk between immune and bone cells for effective bone regeneration. This tight interaction opens the door to new strategies that encompass the development of smart cell-instructive biomaterials which performance covers the events from early inflammation to osteogenesis. The present work links the anti-inflammatory and osteoimmunomodulatory features of synthetic bone grafts to their chemistry and texture, focussing on the cross-talk between macrophages and two major orchestrators of bone healing, namely primary mesenchymal stem cells and osteoblasts. The results emphasize the importance of the microenvironment created through the interaction between the substrate and the immune cells as it can stimulate osteogenic events and subsequently foster bone healing.
Publisher: Elsevier BV
Date: 03-1111
DOI: 10.1016/J.BONE.2018.01.010
Abstract: Osteocytes comprise more than 90% of the cells in bone and are differentiated from osteoblasts via an unknown mechanism. Recently, it was shown that Notch signaling plays an important role in osteocyte functions. To gain insights into the mechanisms underlying the functions of Notch in regulating the transition of osteoblasts to osteocytes, we performed a luciferase assay by cloning the proximal E11 and dentin matrix acidic phosphoprotein 1 (DMP1) promotor regions into pGluc-Basic 2 vectors, which were subsequently transfected into the IDG-SW3 (osteocytes), MC3T3 (osteoblasts) and 293T (non-osteoblastic cells) cell lines. Two approaches were used to activate Notch signaling in vitro. One was a Notch1 extracellular antibody-coated cell culture plate, and the other was transfection of a Hairy/Enhancer of Split 1 (Hes1) overexpression vector. The interaction between the Notch and Wnt signaling pathways was probed by assessing the expression of a series of phosphorylated proteins involved in the cascade of both signaling pathways. Our data suggested that Notch signaling regulates E11 expression through Hes1 activity, while Hes1 solely did not initiate the expression of DMP1. The regulatory function of E11 by Hes1 was not observed in the 293T cell line, indicating a cell context-dependent manner of the Notch signaling pathway. Additionally, we found that Notch inhibited Wnt signaling at the late differentiation stage of osteocytes by both directly repressing phosphorylated Akt and preventing the nuclear aggregation of β-catenin. These findings provide profound understandings of Notch's regulatory function in osteocyte differentiation.
Publisher: Ivyspring International Publisher
Date: 2021
DOI: 10.7150/IJBS.61012
Publisher: Mary Ann Liebert Inc
Date: 12-2014
Publisher: Springer Science and Business Media LLC
Date: 23-01-2019
DOI: 10.1038/S41598-018-36909-9
Abstract: Non-resolved persistent macrophage-mediated synovial inflammation is considered as one of the main drivers of both the establishment and progression of obesity-associated osteoarthritis (OA). Herein, we used clodronate-loaded liposomes (CL) to locally deplete macrophages in the synovial joints to examine the role of macrophages in the progression of obesity-induced OA. Furthermore, resolvin D1 (RvD1), a unique family of pro-resolving lipid mediator derived from the omega-3 polyunsaturated fatty acid, have shown marked potency in changing the pro-inflammatory behaviour of the macrophages. We sought to determine whether RvD1 administration ameliorates obesity-induced OA by resolving macrophage-mediated synovitis. Therapeutic properties of RvD1 and macrophage depletion (CL) were tested for its ability to slow post-traumatic OA (PTOA) in obese mice models. PTOA was induced in C57Bl/6 mice fed with high-fat diet (HFD) by surgically destabilising the meniscus. Firstly, CL treatment showed beneficial effects in reducing synovitis and cartilage destruction in obese mice with PTOA. In vitro treatment with RvD1 decreased the levels of pro-inflammatory markers in CD14+ human macrophages. Furthermore, intra-articular treatment with RvD1 diminishes the progression of OA in the knee joint from mice as follows: (a) decreases macrophages infiltration in synovium, (b) reduces the number of pro-inflammatory macrophages in synovium and (c) improves the severity of synovitis and cartilage degradation. Thus, our results provide new evidence for the potential targeting of macrophages in the treatment of obesity-induced OA.
Publisher: Wiley
Date: 03-2000
DOI: 10.1034/J.1600-051X.2000.027003149.X
Abstract: The regulation of plasminogen activation is a key element in controlling proteolytic events in the extracellular matrix. Our previous studies had demonstrated that in inflamed gingival tissues, tissue-type plasminogen activator (t-PA) is significantly increased in the extracellular matrix of the connective tissue and that interleukin 1beta(IL-1beta) can up regulate the level of t-PA and plasminogen activator inhibitor-2 (PAI-2) synthesis by human gingival fibroblasts. In the present study, the levels of t-PA and PAI-2 in gingival crevicular fluid (GCF) were measured from healthy, gingivitis and periodontitis sites and compared before and after periodontal treatment. Crevicular fluid from106 periodontal sites in 33 patients were collected. 24 sites from 11 periodontitis patients received periodontal treatment after the first s le collection and post-treatment s les were collected 14 days after treatment. All s les were analyzed by enzyme-linked immunosorbent assay (ELISA) for t-PA and PAI-2. The results showed that significantly high levels of t-PA and PAI-2 in GCF were found in the gingivitis and periodontitis sites. Periodontal treatment led to significant decreases of PAI-2, but not t-PA, after 14 days. A significant positive linear correlation was found between t-PA and PAI-2 in GCF (r=0.80, p<0.01). In the healthy group, different sites from within the same subject showed little variation of t-PA and PAI-2 in GCF. However, the gingivitis and periodontitis sites showed large variation. These results suggest a good correlation between t-PA and PAI-2 with the severity of periodontal conditions. This study indicates that t-PA and PAI-2 may play a significant rôle in the periodontal tissue destruction and tissue remodeling and that t-PA and PAI-2 in GCF may be used as clinical markers to evaluate the periodontal diseases and assess treatment.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.ACTBIO.2018.12.049
Abstract: With high incidence rate and unique regeneration features, maxillofacial burr hole bone defects require a specially designed bone defect animal model for the evaluation of related bone regenerative approaches. Although some burr hole defect models have been developed in long bones or calvarial bones, the mandible has unique tissue development origins and regenerative environments. This suggests that the defect model should be prepared in the maxillofacial bone area. After dissecting the anatomic structures of rat mandibles, we found that creating defects in the anterior tooth area avoided damaging important organs and improved animal welfare. Furthermore, the available bone volume at the anterior tooth area was superior to that of the posterior tooth and ascending ramus areas. We then managed to standardize the model by controlling the age, weight and gender of the animal, creating standardized measurement instruments and reducing the variations derived from various operators. We also succeeded in deterring the self-rehabilitation of the proposed model by increasing the defect size. The 6 × 2 mm and 8 × 2 mm defects were found to meet the requirements of bone regenerative studies. This study provided a step-by-step standardized burr hole bone defect model with minimal tissue damage in small animals. The evaluations resulting from this model testify to the in vitro outcomes of the proposed regenerative approaches and provide preliminary screening data for further large animal and clinical trials. Therefore, the inclusion of this model may optimize the evaluation systems for maxillofacial burr hole bone defect regenerative approaches. STATEMENT OF SIGNIFICANCE: Unremitting effort has been devoted to the development of bone regenerative materials to restore maxillofacial burr hole bone defects because of their high clinical incidence rate. In the development of these biomaterials, in vivo testing in small animals is necessary to evaluate the effects of candidate biomaterials. However, little has been done to develop such defect models in small animals. In this study, we developed a standardized rat mandible burr hole bone defect model with minimal injury to the animals. A detailed description and supplementary video were provided to guide the preparation. The development of this model optimizes the maxillofacial bone regenerative approach evaluation system.
Publisher: Elsevier BV
Date: 03-2022
Publisher: Informa UK Limited
Date: 25-05-2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8BM00287H
Abstract: Blood prefabricated hydroxyapatite/tricalcium phosphate induces ectopic vascularized bone formation via modulating the osteoimmune environment.
Publisher: Springer Science and Business Media LLC
Date: 02-2010
Publisher: Springer Nature Singapore
Date: 2023
Publisher: Future Science Ltd
Date: 09-2011
DOI: 10.4155/TDE.11.84
Abstract: The use of mesoporous bioactive glasses (MBG) for drug delivery and bone tissue regeneration has grown significantly over the past 5 years. In this article, we highlight recent advances made in the preparation of MBG particles, spheres, fibers and scaffolds. The advantages of MBG for drug delivery and bone scaffold applications are related to this material’s well-ordered mesopore channel structure, superior bioactivity and its capability to deliver both hydrophilic and hydrophobic drugs. A brief forward-looking perspective on the potential clinical applications of MBG in regenerative medicine is also discussed.
Publisher: Informa UK Limited
Date: 24-02-2017
DOI: 10.1080/00016357.2017.1292427
Abstract: To investigate the effect of local hIL-10 gene therapy on experimental periodontitis in rats and to elucidate the mechanism underlying this effect. Experimental periodontitis was induced in ovariectomized (OVX) rats using a silk ligature. We then injected 5 μg of hIL-10 plasmid with 5 μl of liposomes or 5 μg of vector plasmid with 5 μl of liposomes into the palatal side of the gingival mucosa of the upper left second molar once every two days. The rats were killed 48 hours after the seventh injection. The body weight bone mineral density of the whole body, pelvis and spine resorption of the alveolar bone and number of cytokine-positive cells were measured to determine the effects of hIL-10 on the periodontal tissue. hIL-10 was expressed in periodontal tissues after local gene delivery. The expressed hIL-10 protein inhibited alveolar bone resorption and downregulated IL-1β, IL-6, TNF-α, RANKL and MMP-8 in the periodontal ligament in the root furcation region. Local hIL-10 gene transfer suppressed alveolar bone resorption in OVX rats, and this effect was probably associated with the decline in the expression of pro-inflammatory cytokines in the periodontal tissues.
Publisher: MDPI AG
Date: 26-03-2018
DOI: 10.3390/MET8040212
Publisher: S. Karger AG
Date: 28-10-2009
DOI: 10.1159/000166547
Abstract: i Background: /i Stem cell-based therapies have shown great promise in regenerative medicine and continue to generate wide interest in future clinical applications. However, the issue of storage and preservation of stem cells, for future clinical applications, still requires extensive investigation. i Objective: /i The purpose of this study was to evaluate the effect of cryopreservation on the regenerative capacity of bone marrow stem cells in periodontal defects in dogs. i Materi /i i als and Methods: /i Bone marrow mesenchymal stem cells (BMSCs) were obtained from 5 beagle dogs. After cryopreservation for 1 month, cell viability, surface adherence ability, alkaline phosphatase activity and mineralized nodule formation were assessed. Twenty-six periodontal fenestration defects (5 × 5 mm) were created at a location 5 mm apical to the cemento-enamel junction in experimental teeth. Cryopreserved BMSCs were transplanted into the defects using a collagen scaffold carrier. Freshly isolated BMSCs and collagen scaffold alone were used as controls. All animals were sacrificed 8 weeks after surgery, and specimens were evaluated by histomorphometry. i Results: /i Cryopreservation had no discernible negative effect on BMSC growth and differentiation in vitro. Both freshly isolated and cryopreserved BMSC transplantations induced significantly better periodontal regeneration with newly formed cementum, alveolar bone and periodontal ligament compared with the application of collagen scaffold alone. i Conclusion: /i Cryopreserved BMSCs showed no altered regenerative capacity compared with freshly isolated BMSCs in the application of periodontal regeneration.
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.JOCA.2012.07.007
Abstract: The aim of this study was to demonstrate the potential of near-infrared (NIR) spectroscopy for categorizing cartilage degeneration induced in animal models. Three models of osteoarthritic degeneration were induced in laboratory rats via one of the following methods: (1) menisectomy (MSX) (2) anterior cruciate ligament transection (ACLT) and (3) intra-articular injection of mono-ido-acetate (1 mg) (MIA), in the right knee joint, with 12 rats per model group. After 8 weeks, the animals were sacrificed and tibial knee joints were collected. A custom-made near-infrared (NIR) probe of diameter 5 mm was placed on the cartilage surface and spectral data were acquired from each specimen in the wave number range 4,000-12,500 cm(-1). Following spectral data acquisition, the specimens were fixed and Safranin-O staining was performed to assess disease severity based on the Mankin scoring system. Using multivariate statistical analysis based on principal component analysis and partial least squares regression, the spectral data were then related to the Mankin scores of the s les tested. Mild to severe degenerative cartilage changes were observed in the subject animals. The ACLT models showed mild cartilage degeneration, MSX models moderate, and MIA severe cartilage degenerative changes both morphologically and histologically. Our result demonstrates that NIR spectroscopic information is capable of separating the cartilage s les into different groups relative to the severity of degeneration, with NIR correlating significantly with their Mankin score (R(2) = 88.85%). We conclude that NIR is a viable tool for evaluating articular cartilage health and physical properties such as change in thickness with degeneration.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.BIOMATERIALS.2017.08.027
Abstract: Although much research has gone into the design of nanomaterials, inflammatory response still impedes the capacity of nanomaterial-induced tissue regeneration. In-situ incorporation of nutrient elements in silica-based biomaterials has emerged as a new option to endow the nanomaterials modulating biological reactions. In this work, europium-doped mesoporous silica nanospheres (Eu-MSNs) were successfully synthesized via a one-pot method. The nanospheres (size of 280-300 nm) possess uniformly spherical morphology and mesoporous structure, and well distributed Eu elements. The nanospheres show distinct fluorescent property at 615 nm for potential bio-labeling. Noticeably, the Eu-MSNs stimulate pro-inflammatory response of macrophages and induce a modulated immune microenvironment, which further activates the osteogenic differentiation of bone marrow stromal cells (BMSCs) as well as angiogenic activity of human umbilical vein endothelial cells (HUVECs). During the process, osteogenesis-related genes (e.g. ALP, OCN, OPN and COL-I) of BMSCs, and angiogenesis-related genes (e.g. CD31, MMP9, VEGFR1/2, and PDGFRα/β) of HUVECs were significantly upregulated by Eu-MSNs modulating immune environment of macrophages. The in vivo study further demonstrated that the Eu-MSNs could not only stimulate osteogenesis by accelerating the new bone formation at critical-sized cranial defect site, but also support the blood vessel formation as well as collagen deposition and re-epithelialization at chronic skin wound sites, showing an improved angiogenesis activity when comparing with MSNs alone. Given the easy handling characteristics and extensive application potential, the results suggest that Eu-MSNs could be used as immunity-modulated osteogenesis/angiogenesis agent for skin and bone regeneration.
Publisher: Wiley
Date: 21-08-2009
DOI: 10.1111/J.1600-0765.2008.01174.X
Abstract: Human periodontal ligament cells play a pivotal role in maintaining periodontal ligament space, contain progenitors that are able to differentiate into cementoblasts/osteoblasts and have a tremendous potential to regenerate periodontal tissue. However, the exact molecular mechanisms governing the differentiation mechanisms of progenitors in periodontal ligament cells remain largely unknown. This study was carried out to investigate the differentially expressed proteins involved in the osteogenic differentiation of progenitors presented in periodontal ligament cells. Using two-dimensional gel electrophoresis, mass spectrometry and peptide mass fingerprinting, we analyzed the differential protein profiles of periodontal ligament cells undergoing mineralization. Compared with undifferentiated periodontal ligament cells, 61 proteins in periodontal ligament cells undergoing differentiation showed at least a 1.5-fold change in intensity, of which 29 differentially expressed proteins were successfully identified by matrix-assisted laser-desorption ionization time-of-flight mass spectrometry. The expression of some of the identified proteins was further confirmed by western blotting and reverse transcription-polymerase chain reaction analysis. The identified proteins were cytoskeleton proteins and cytoskeleton-associated proteins, nuclear proteins and cell membrane-bound molecules. Our results suggest that the proteins identified in this study may be associated with the unique function of periodontal ligament cells in maintaining periodontal tissue homeostasis, thus providing a comprehensive reference for understanding and investigating in greater detail the molecular mechanisms of periodontal ligament cells involved in periodontal regeneration.
Publisher: Springer Science and Business Media LLC
Date: 28-08-2015
Publisher: Springer Science and Business Media LLC
Date: 2013
DOI: 10.1186/AR4333
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2JM34395A
Publisher: Springer Singapore
Date: 2018
DOI: 10.1007/978-981-13-0947-2_5
Abstract: In spite of inherent regenerative ability of bone, large amounts of fracture patients still display delayed or compromised bone healing due to patients' age status, trauma severity or the developmental anomalies or infections, which requires therapeutic intervention. Bone regeneration involves different cells (immune cells, progenitors and mesenchymal stem cells, etc) and subsequent signaling molecules (chemokines, cytokines and growth factors, etc). The quantity and quality of immune cells influx into the site of injury and the subsequent cytokine production form a unique osteoimmune environment. Current strategies on repairing bone defects have largely focused on the development of suitable bone substitute materials, which may have potential osteoinductive, and/or osteoconductive properties. Various studies have been reported to develop the immuno-active or immunomodulatory biomaterials, which could fully explore the early osteoimmune environment in order to achieve better bone regeneration.
Publisher: Springer Science and Business Media LLC
Date: 04-09-2022
DOI: 10.1186/S10020-022-00530-4
Abstract: It is well-known that both macrophages and osteocytes are critical regulators of osteogenesis and osteoclastogenesis, yet there is limited understanding of the macrophage-osteocyte interaction, and how their crosstalk could affect bone homeostasis and mineralization. This research therefore aims to investigate the effects of macrophage polarization on osteocyte maturation and mineralization process. A macrophage-derived conditioned medium based osteocyte culture was set up to investigate the impact of macrophages on osteocyte maturation and terminal mineralization. Surgically induced osteoarthritis (OA) rat model was used to further investigate the macrophage-osteocyte interaction in inflammatory bone remodeling, as well as the involvement of the Notch signaling pathway in the mineralization process. Our results identified that osteocytes were confined in an immature stage after the M1 macrophage stimulation, showing a more rounded morphology, higher expression of early osteocyte marker E11, and significantly lower expression of mature osteocyte marker DMP1. Immature osteocytes were also found in inflammatory bone remodeling areas, showing altered morphology and mineralized structures similar to those observed under the stimulation of M1 macrophages in vitro, suggesting that M1 macrophages negatively affect osteocyte maturation, leading to abnormal mineralization. The Notch signaling pathway was found to be down regulated in M1 macrophage-stimulated osteocytes as well as osteocytes in inflammatory bone. Overexpression of the Notch signaling pathway in osteocytes showed a significant circumvention on the negative effects from M1 macrophage. Taken together, our findings provide valuable insights into the mechanisms involved in abnormal bone mineralization under inflammatory conditions.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.ARTHRO.2014.04.097
Abstract: The purpose of this study was to demonstrate the potential of near infrared (NIR) spectroscopy for characterizing the health and degenerative state of articular cartilage based on the components of the Mankin score. Three models of osteoarthritic degeneration induced in laboratory rats by anterior cruciate ligament (ACL) transection, meniscectomy (MSX), and intra-articular injection of monoiodoacetate (1 mg) (MIA) were used in this study. Degeneration was induced in the right knee joint each model group consisted of 12 rats (N = 36). After 8 weeks, the animals were euthanized and knee joints were collected. A custom-made diffuse reflectance NIR probe of 5-mm diameter was placed on the tibial and femoral surfaces, and spectral data were acquired from each specimen in the wave number range of 4,000 to 12,500 cm(-1). After spectral data acquisition, the specimens were fixed and safranin O staining (SOS) was performed to assess disease severity based on the Mankin scoring system. Using multivariate statistical analysis, with spectral preprocessing and wavelength selection technique, the spectral data were then correlated to the structural integrity (SI), cellularity (CEL), and matrix staining (SOS) components of the Mankin score for all the s les tested. ACL models showed mild cartilage degeneration, MSX models had moderate degeneration, and MIA models showed severe cartilage degenerative changes both morphologically and histologically. Our results reveal significant linear correlations between the NIR absorption spectra and SI (R(2) = 94.78%), CEL (R(2) = 88.03%), and SOS (R(2) = 96.39%) parameters of all s les in the models. In addition, clustering of the s les according to their level of degeneration, with respect to the Mankin components, was also observed. NIR spectroscopic probing of articular cartilage can potentially provide critical information about the health of articular cartilage matrix in early and advanced stages of osteoarthritis (OA). This rapid nondestructive method can facilitate clinical appraisal of articular cartilage integrity during arthroscopic surgery.
Publisher: Oxford University Press (OUP)
Date: 09-11-2006
DOI: 10.1634/STEMCELLS.2006-0168
Abstract: Swine-derived MSCs were efficiently isolated and extensively expanded using a low fetal serum content growth medium to which selected growth factors were added. After ≥96 cell population doublings (PDs), MSCs were devoid of cytogenetic abnormalities. In vitro chondrogenic and osteogenic differentiation capacity was preserved after 80 PDs. To test therapeutic efficacy, 1 × 106 80-PD MSCs were injected directly into the peri-infarct zone of hearts of immunodeficient (non-obese diabetic/severe combined immunodeficient) mice at the time of acute myocardial infarction. Engrafted MSCs survived in the infarcted hearts for at least 4 weeks. Echocardiography at 2 and 4 weeks postinfarction revealed a significant preservation of the left ventricular ejection fractions of infarct hearts receiving MSCs compared with infarct hearts receiving saline. Peri-infarct zone capillarity was better preserved in MSC-treated hearts than other infarct groups of hearts, but infarct size was comparable in all groups. Only rare engrafted MSCs expressed cardiac-specific or endothelial cell-specific markers. Hence, 80-PD MSCs retained the capacity to promote functional improvement in the infarcted heart despite minimal differentiation of MSCs into cardiomyocytes or endothelial cells. These data suggest that the beneficial effects of MSC transplantation most likely result from the trophic effects of MSC-released substances on native cardiac and vascular cells. The capacity to massively expand MSC lines without loss of therapeutic efficacy may prove to be useful in the clinical setting where “off the shelf” MSCs may be required for interventions in patients with acute coronary syndromes.
Publisher: OAE Publishing Inc.
Date: 2023
DOI: 10.20517/MICROSTRUCTURES.2023.05
Abstract: Biomineralization is a process that leads to the formation of hierarchically arranged structures in mineralized tissues, such as bone and teeth. Extensive research has been conducted on the crystals in bones and teeth, with the aim of understanding the underlying mechanisms of the mineralization process. Pathological/ectopic mineralization, such as kidney stones, calcific tendinitis, and skeletal fluorosis, shares some similar features but different mechanisms to physiological mineralization. A better understanding will provide new perspectives for treating pathological/ectopic mineralization-related diseases. This review provides an overview of the mechanisms of the crystallization and growth of crystals in physiological and pathological conditions from a chemistry perspective. By linking the microstructures and functions of crystals formed in both conditions, potential approaches are proposed to treat pathological/ectopic mineralization-related diseases.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.BIOMATERIALS.2018.07.058
Abstract: Immune cells are sensitive to the microstructural and textural properties of materials. Tuning the structural features of synthetic bone grafts could be a valuable strategy to regulate the specific response of the immune system, which in turn modulates the activity of bone cells. The aim of this study was to analyse the effect of the structural characteristics of biomimetic calcium deficient hydroxyapatite (CDHA) on the innate immune response of macrophages and the subsequent impact on osteogenesis and osteoclastogenesis. Murine RAW 264.7 cells were cultured, under standard and inflammatory conditions, on chemically identical CDHA substrates that varied in microstructure and porosity. The impact on osteogenesis was evaluated by incubating osteoblastic cells (SaOS-2) with RAW-CDHA conditioned extracts. The results showed that macrophages were sensitive to different textural and structural properties of CDHA. Under standard conditions, the impact of inflammatory cytokine production by RAW cells cultured on CDHA played a significant role in the degradation of substrates, suggesting the impact of resorptive behaviour of RAW cells on biomimetic surfaces. Osteoblast differentiation was stimulated by the conditioned media collected from RAW cells cultured on needle-like nanostructured CDHA. The results demonstrated that needle-like nanostructured CDHA was able to generate a favourable osteoimmune environment to regulate osteoblast differentiation and osteogenesis. Under inflammatory conditions, the incubation of RAW cells with less porous CDHA resulted in a decreased gene expression and release of pro-inflammatory cytokines.
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/316134
Abstract: To investigate the correlation between postmenopausal osteoporosis (PMO) and the pathogenesis of periodontitis, ovariectomized rats were generated and the experimental periodontitis was induced using a silk ligature. The inflammatory factors and bone metabolic markers were measured in the serum and periodontal tissues of ovariectomized rats using an automatic chemistry analyzer, enzyme-linked immunosorbent assays, and immunohistochemistry. The bone mineral density of whole body, pelvis, and spine was analyzed using dual-energy X-ray absorptiometry and image analysis. All data were analyzed using SPSS 13.0 statistical software. It was found that ovariectomy could upregulate the expression of interleukin- (IL-)6, the receptor activator of nuclear factor- κ B ligand (RANKL), and osteoprotegerin (OPG) and downregulate IL-10 expression in periodontal tissues, which resulted in progressive alveolar bone loss in experimental periodontitis. This study indicates that changes of cytokines and bone turnover markers in the periodontal tissues of ovariectomized rats contribute to the damage of periodontal tissues.
Publisher: Springer Science and Business Media LLC
Date: 26-12-2022
DOI: 10.1186/S40824-022-00323-0
Abstract: Transepithelial medical devices are increasing utilized in clinical practices. However, the damage of continuous natural epithelial barrier has become a major risk factor for the failure of epithelium-penetrating implants. How to increase the “epithelial barrier structures” (focal adhesions, hemidesmosomes, etc . ) becomes one key research aim in overcoming this difficulty. Directly targeting the in situ “epithelial barrier structures” related proteins (such as fibronectin) absorption and functionalization can be a promising way to enhance interface-epithelial integration. Herein, we fabricated three plasma polymerized bio-interfaces possessing controllable surface chemistry. Their capacity to adsorb and functionalize fibronectin (FN) from serum protein was compared by Liquid Chromatography-Tandem Mass Spectrometry. The underlying mechanisms were revealed by molecular dynamics simulation. The response of gingival epithelial cells regarding the formation of epithelial barrier structures was tested. Plasma polymerized surfaces successfully directed distinguished protein adsorption profiles from serum protein pool, in which plasma polymerized allylamine (ppAA) surface favored adsorbing adhesion related proteins and could promote FN absorption and functionalization via electrostatic interactions and hydrogen bonds, thus subsequently activating the ITG β1-FAK-mTOR signaling and promoting gingival epithelial cells adhesion. This study offers an effective perspective to overcome the current dilemma of the inferior interface-epithelial integration by in situ protein absorption and functionalization, which may advance the development of functional transepithelial biointerfaces. Tuning the surface chemistry by plasma polymerization can control the adsorption of fibronectin and functionalize it by exposing functional protein domains. The functionalized fibronectin can bind to human gingival epithelial cell membrane integrins to activate epithelial barrier structure related signaling pathway, which eventually enhances the formation of epithelial barrier structure.
Publisher: Elsevier BV
Date: 02-2022
Publisher: Bentham Science Publishers Ltd.
Date: 27-01-2009
Publisher: Springer Science and Business Media LLC
Date: 03-03-2015
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.BIOMATERIALS.2012.05.061
Abstract: Lithium (Li) has been widely used as a long-term mood stabilizer in the treatment of bipolar and depressive disorders. Li(+) ions are thought to enhance the remyelination of peripheral nerves and also stimulate the proliferation of neural progenitor cells and retinoblastoma cells via activation of the Wnt/β-catenin signalling pathway. Until now there have been no studies reporting the biological effects of released Li(+) in bioactive scaffolds on cemetogenesis in periodontal tissue engineering applications. In this study, we incorporated parts of Li(+) ions into the mesoporous bioactive glass (MBG) scaffolds and showed that this approach yielded scaffolds with a favourable composition, microstructure and mesopore properties for cell attachment, proliferation, and cementogenic differentiation of human periodontal ligament-derived cells (hPDLCs). We went on to investigate the biological effects of Li(+) ions themselves on cell proliferation and cementogenic differentiation. The results showed that 5% Li(+) ions incorporated into MBG scaffolds enhanced the proliferation and cementogenic differentiation of hPDLCs on scaffolds, most likely via activation of Wnt/β-catenin signalling pathway. Further study demonstrated that Li(+) ions by themselves significantly enhanced the proliferation, differentiation and cementogenic gene expression of PDLCs. Our results indicate that incorporation of Li(+) ions into bioactive scaffolds is a viable means of enhancing the Wnt canonical signalling pathway to stimulate cementogenic differentiation of PDLCs.
Publisher: Mary Ann Liebert Inc
Date: 11-2022
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.BONE.2007.08.048
Abstract: In both physiological and pathological processes, periosteum plays a determinant role in bone formation and fracture healing. However, no specific report is available so far focusing on the detailed structural and major cellular differences between the periostea covering different bone surface in relation to ageing. The aim of this study is to compare the structural and cellular differences in diaphyseal and metaphyseal periostea in different aged rats using histological and immunohistochemical methods. Four female Lewis rats from each group of juvenile (7 weeks old), mature (7 months old) and aged groups (2 years old) were sacrificed and the right femur of each rat was retrieved, fixed, decalcified and embedded. Five-micrometer thick serial sagittal sections were cut and stained with Hematoxylin and Eosin, Stro-1 (stem cell marker), F4/80 (macrophage marker), TRAP (osteoclast marker) and vWF (endothelial cell marker). One-millimeter lengths of middle diaphyseal and metaphyseal periosteum were selected for observation. The thickness, total cell number and positive cell number for each antibody were measured and compared in each periosteal area and different aged groups. The results were subjected to two-way ANOVA and SNK tests. The results showed that the thickness and cell number in diaphyseal periosteum decreased with age (p<0.001). In comparison with diaphyseal area, the thickness and cell number in metaphyseal periosteum were much higher (p 0.05). However, the juvenile rats had more Stro1(+), F4/80(+) cells and blood vessels and fewer TRAP(+) cells in different periosteal areas compared with other groups (p<0.001). The aged rats showed much fewer Stro1(+) cells, but more F4/80(+), TRAP(+) cells and blood vessels in the cambial layer of metaphyseal periosteum (p<0.001). In conclusion, structure and cell population of periosteum appear to be both age-related and site-specific. The metaphyseal periosteum of aged rats seems more destructive than diaphyseal part and other age groups. Macrophages in the periosteum may play a dual important role in osteogenesis and osteoclastogenesis.
Publisher: Wiley
Date: 30-12-2021
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7NR05913B
Abstract: A nanotopography-based strategy to precisely manipulate the osteoimmune environment for bone regeneration.
Publisher: American Chemical Society (ACS)
Date: 21-04-2021
Publisher: Elsevier BV
Date: 04-2008
Publisher: Elsevier BV
Date: 05-2019
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.MSEC.2021.112297
Abstract: Peri-implantitis is a bacterially induced inflammatory disease which affects the hard and soft tissues around a dental implant. Microbial biofilm formation is an important causative factor in peri-implantitis. The aim of this study is to develop an effective multifunctional surface coating for antimicrobial property and to counteract oral biofilm-associated infections via a single polydopamine copper coating (PDAM@Cu) on titanium implant surface to regulate endogenous nitric oxide (NO) generation. PDAM@Cu coatings were made with different concentrations of CuCl NO release rates could be controlled with different Cu concentration in PDAM@Cu coatings. NO generated from the PDAM@Cu coatings effectively induced dispersal of biofilms shown by the reduction in biofilm biomass as well as reduced biofilm attachment in s les prepared with blood and NO donors. Cu ions released from the PDAM@Cu coatings resulted in killing of the dispersed bacteria, which was evidenced by the live/dead cell staining and reduced metabolic activity noted from the XTT assay. In contrast, s les prepared with saliva showed no significant reduction in biofilms, indicating the important effect of endogenously generated NO on biofilm dispersal. In conclusion, PDAM@Cu coatings with NO generating surfaces have a dual anti-biofilm function, with a synergistic effect on biofilm dispersal from regulated NO generation and bactericidal effects from Cu ions from the coatings.
Publisher: Springer Berlin Heidelberg
Date: 12-2016
Publisher: Springer Berlin Heidelberg
Date: 12-2016
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.BONE.2012.12.042
Abstract: Determining the properties and integrity of subchondral bone in the developmental stages of osteoarthritis, especially in a form that can facilitate real-time characterization for diagnostic and decision-making purposes, is still a matter for research and development. This paper presents relationships between near infrared absorption spectra and properties of subchondral bone obtained from 3 models of osteoarthritic degeneration induced in laboratory rats via: (i) menisectomy (MSX) (ii) anterior cruciate ligament transaction (ACL) and (iii) intra-articular injection of mono-ido-acetate (1mg) (MIA), in the right knee joint, with 12 rats per model group (N=36). After 8weeks, the animals were sacrificed and knee joints were collected. A custom-made diffuse reflectance NIR probe of diameter 5mm was placed on the tibial surface and spectral data were acquired from each specimen in the wavenumber range 4000-12500cm(-1). After spectral acquisition, micro computed tomography (micro-CT) was performed on the s les and subchondral bone parameters namely: bone volume (BV) and bone mineral density (BMD) were extracted from the micro-CT data. Statistical correlation was then conducted between these parameters and regions of the near infrared spectra using multivariate techniques including principal component analysis (PCA), discriminant analysis (DA), and partial least squares (PLS) regression. Statistically significant linear correlations were found between the near infrared absorption spectra and subchondral bone BMD (R(2)=98.84%) and BV (R(2)=97.87%). In conclusion, near infrared spectroscopic probing can be used to detect, qualify and quantify changes in the composition of the subchondral bone, and could potentially assist in distinguishing healthy from OA bone as demonstrated with our laboratory rat models.
Publisher: Wiley
Date: 06-2001
DOI: 10.1359/JBMR.2001.16.6.1068
Abstract: The hypothesis that growth hormone (GH) up-regulates the expression of enzymes, matrix proteins, and differentiation markers involved in mineralization of tooth and bone matrices was tested by the treatment of Lewis dwarf rats with GH over 5 days. The molar teeth and associated alveolar bone were processed for immunohistochemical demonstration of bone morphogenetic proteins 2 and 4 (BMP-2 and -4), bone morphogenetic protein type IA receptor (BMPR-IA), bone alkaline phosphatase (ALP), osteocalcin (OC), osteopontin (OPN), bone sialoprotein (BSP), and E11 protein (E11). The cementoblasts, osteoblasts, and periodontal ligament (PDL) cells responded to GH by expressing BMP-2 and -4, BMPR-IA, ALP, OC, and OPN and increasing the numbers of these cells. No changes were found in patterns of expression of the late differentiation markers BSP and E11 in response to GH. Thus, GH evokes expression of bone markers of early differentiation in cementoblasts, PDL cells, and osteoblasts of the periodontium. We propose that the induction of BMP-2 and -4 and their receptor by GH compliments the role of GH-induced insulin-like growth factor 1 (IGF-1) in promoting bone and tooth root formation.
Publisher: Springer International Publishing
Date: 12-2017
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.BIOSYSTEMS.2008.05.030
Abstract: Osteoarthritis (OA), the most common form of arthritis is a degenerative joint disease, which causes severe long-term pain and physical disability. It is becoming more important to improve diagnosis and understanding of the disease process and subsequently develop new intervention to delay or even reverse the disease progress. Our study was designed to combine two relatively novel treatment techniques, autologous chondrocyte transplantation (ACT) and proposed application of medical remedies based on surface-active phospholipids. To this end we exposed chondrocyte to culture environments with mixtures of culture medium and phospholipid solutions. Following various culture periods, cell survival and well-being were determined by measuring proliferation and assessing morphological features, and comparing these with the behaviour of cells grown in classical which were not mixed with surfactant, i.e., control culture medium. Scanning electron microscopy and light microscopy demonstrate that the cells exposed to mixtures with surfactant were as healthy as those in the control environment with polygonal morphology, while proliferation assay indicated a noticeably higher level of proliferation over similar periods, for cells cultured in media that was mixed with surfactants. Also, the cells in media with unsaturated surfactants responded better than those cultured in mixtures containing saturated surfactant.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.ACTBIO.2016.06.035
Abstract: Compromised bone quality and/or healing in osteoporosis are recognised risk factors for impaired dental implant osseointegration. This study examined the effects of (1) experimentally induced osteoporosis on titanium implant osseointegration and (2) the effect of modified implant surface topography on osseointegration under osteoporosis-like conditions. Machined and micro-roughened surface implants were placed into the maxillary first molar root socket of 64 ovariectomised and sham-operated Sprague-Dawley rats. Subsequent histological and SEM observations showed tissue maturation on the micro-rough surfaced implants in ovariectomised animals as early as 3days post-implantation. The degree of osseointegration was also significantly higher around the micro-rough implants in ovariectomised animals after 14days of healing although by day 28, similar levels of osseointegration were found for all test groups. The micro-rough implants significantly increased the early (day 3) gene expression of alkaline phosphatase, osteocalcin, receptor activator of nuclear factor kappa-B ligand and dentin matrix protein 1 in implant adherent cells. By day 7, the expression of inflammatory genes decreased while the expression of the osteogenic markers increased further although there were few statistically significant differences between the micro-rough and machined surfaces. Osteocyte morphology was also affected by estrogen deficiency with the size of the cells being reduced in trabecular bone. In conclusion, estrogen deficiency induced osteoporotic conditions negatively influenced the early osseointegration of machined implants while micro-rough implants compensated for these deleterious effects by enhancing osteogenic cell differentiation on the implant surface. Lower bone density, poor bone quality and osseous microstructural changes are all features characteristic of osteoporosis that may impair the osseointegration of dental implants. Using a clinically relevant trabecular bone model in the rat maxilla, we demonstrated histologically that the negative effects of surgically-induced osteoporosis on osseointegration could be ameliorated by the biomaterial's surface topography. Furthermore, gene expression analysis suggests this may be a result of enhanced osteogenic cell differentiation on the implant surface.
Publisher: Mary Ann Liebert Inc
Date: 05-2016
Abstract: Periodontal inflammation can inhibit cell differentiation of periodontal ligament cells (PDLCs), resulting in decreased bone/cementum regeneration ability. The Wnt signaling pathway, including canonical Wnt/β-catenin signaling and noncanonical Wnt/Ca(2+) signaling, plays essential roles in cell proliferation and differentiation during tooth development. However, little is still known whether noncanonical Wnt/Ca(2+) signaling cascade could regulate cementogenic/osteogenic differentiation capability of PDLCs within an inflammatory environment. Therefore, in this study, human PDLCs (hPDLCs) and their cementogenic differentiation potential were investigated in the presence of cytokines. The data demonstrated that both cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) inhibited cell proliferation, relative alkaline phosphatase activity, bone/cementum-related gene rotein expression, and canonical Wnt pathway-related gene rotein expression in hPDLCs. Interestingly, both cytokines upregulated the noncanonical Wnt/Ca(2+) signaling-related gene and protein expression in hPDLCs. When the Wnt/Ca(2+) pathway was blocked by Ca(2+)/calmodulin-dependent protein kinase II inhibitor KN93, even in the presence of IL-6 and TNF-α, cementogenesis could be stimulated in hPDLCs. Our data indicate that the Wnt/Ca(2+) pathway plays an inhibitory role on PDLC cementogenic differentiation in inflammatory microenvironments. Therefore, targeting the Wnt/Ca(2+) pathway may provide a novel therapeutic approach to improve periodontal regeneration for periodontal diseases.
Publisher: Elsevier BV
Date: 03-2018
Publisher: Elsevier BV
Date: 07-2016
Publisher: Wiley
Date: 16-04-2023
Abstract: Critical‐sized bone defects, especially for irregular shapes, remain a significant challenge in orthopedics. Although various biomaterials are developed for bone regeneration, their application for repair of irregular bone defects is limited by the complicated preparation procedures involved, and their lack of shape‐adaptive capacity, physiological adhesion, and potent osteogenic bioactivity. In the present study, a simple strategy of precipitation by introducing tannic acid (TA) with abundant phenolic hydroxyl groups and Fe 3 O 4 nanoparticles, as metal‐phenolic networks (MPN), is developed to easily prepare a fast gelling, shape‐adaptive, and highly adhesive regenerated silk fibroin (RSF)/TA/Fe 3 O 4 hydrogel system that can respond to a static magnetic field (SMF). The RSF/TA/Fe 3 O 4 hydrogel exhibits sufficient adhesion in biological microenvironments and good osteogenic effect in vitro and in vivo, under an external SMF, and thus, can be applied to repair critical‐sized bone defects. Moreover, bioinformatics analysis reveals that the synergistic mechanism of Fe 3 O 4 NPs and SMF on osteogenic effects can be promotion of osteoblast differentiation via activation of the cyclic guanosine monophosphate (cGMP) rotein kinase G (PKG)/extracellular signal‐regulated kinase (ERK) signaling pathway. This study provides a promising biomaterial with potential clinical application for the future treatment of (irregular) critical‐sized bone defects.
Publisher: Wiley
Date: 05-12-2011
DOI: 10.1111/J.1600-0765.2011.01443.X
Abstract: A number of bone-filling materials containing calcium (Ca(2+) ) and phosphate (P) ions have been used in the repair of periodontal bone defects however, the effects that local release of Ca(2+) and P ions has on biological reactions are not fully understood. In this study, we investigated the effects of various levels of Ca(2+) and P ions on the proliferation, osteogenic differentiation and mineralization of human periodontal ligament cells (hPDLCs). The hPDLCs were obtained using an explant culture method. Defined concentrations and ratios of ionic Ca(2+) to inorganic P were added to standard culture and osteogenic induction media. The ability of hPDLCs to proliferate in these growth media was assayed using the Cell Counting Kit-8. Cell apoptosis was evaluated by the fluorescein isothiocyanate-annexin V ropidium iodide double-staining method. Osteogenic differentiation and mineralization were investigated by morphological observations, alkaline phosphatase activity and Alizarin Red S/von Kossa staining. The mRNA expression of osteogenic related markers was analysed using RT-PCR. Within the ranges of Ca(2+) and P ion concentrations tested, we observed that increased concentrations of Ca(2+) and P ions enhanced cell proliferation and formation of mineralized matrix nodules, whereas alkaline phosphatase activity was reduced. The RT-PCR results showed that elevated concentrations of Ca(2+) and P ions led to a general increase of Runx2 mRNA expression and decreased alkaline phosphatase mRNA expression, but gave no clear trend on osteocalcin mRNA levels. The concentrations and ratios of Ca(2+) and P ions could significantly influence proliferation, differentiation and mineralization of hPDLCs. Within the range of concentrations tested, we found that the combination of 9.0 mm Ca(2+) ions and 4.5 mm P ions were the optimal concentrations for proliferation, differentiation and mineralization in hPDLCs.
Publisher: Oxford University Press (OUP)
Date: 07-2014
DOI: 10.1093/RHEUMATOLOGY/KEU262
Abstract: The aim of this study was to test the possible involvement, relevance and significance of dentin matrix protein 1 (DMP1) in chondrocyte redifferentiation and OA. To examine the function of DMP1 in vitro, bone marrow stromal cells (BMSCs) and articular chondrocytes (ACs) were isolated and differentiated in micromasses in the presence or absence of DMP1 small interfering RNA and analysed for chondrogenic phenotype. The association of DMP1 expression with OA progression was analysed time dependently in the OA menisectomy rat model and in grade-specific OA human s les. It was found that DMP1 was strongly related to chondrogenesis, which was evidenced by the strong expression of DMP1 in the 14.5-day mouse embryonic cartilage development stage and in femoral heads of post-natal days 0 and 4. In vitro chondrogenesis in BMSCs and ACs was accompanied by a gradual increase in DMP1 expression at both the gene and protein levels. In addition, knockdown of DMP1 expression led to decreased chondrocyte marker genes, such as COL2A1, ACAN and SOX9, and an increase in the expression of COL10A and MMP13 in ACs. Moreover, treatment with IL-1β, a well-known catabolic culprit of proteoglycan matrix loss, significantly reduced the expression of DMP1. Furthermore, we also observed the suppression of DMP1 protein in a grade-specific manner in knee joint s les from patients with OA. In the menisectomy-induced OA model, an increase in the Mankin score was accompanied by the gradual loss of DMP1 expression. Observations from this study suggest that DMP1 may play an important role in maintaining the chondrogenic phenotype and its possible involvement in altered cartilage matrix remodelling and degradation in disease conditions like OA.
Publisher: Springer Science and Business Media LLC
Date: 11-2015
Publisher: Springer Berlin Heidelberg
Date: 12-2017
Publisher: MDPI AG
Date: 16-12-2022
DOI: 10.3390/GELS8120829
Abstract: The traditional two-dimensional (2D) cell culture methods have a long history of mimicking in vivo cell growth. However, these methods cannot fully represent physiological conditions, which lack two major indexes of the in vivo environment one is a three-dimensional 3D cell environment, and the other is mechanical stimulation therefore, they are incapable of replicating the essential cellular communications between cell to cell, cell to the extracellular matrix, and cellular responses to dynamic mechanical stimulation in a physiological condition of body movement and blood flow. To solve these problems and challenges, 3D cell carriers have been gradually developed to provide a 3D matrix-like structure for cell attachment, proliferation, differentiation, and communication in static and dynamic culture conditions. 3D cell carriers in dynamic culture systems could primarily provide different mechanical stimulations which further mimic the real in vivo microenvironment. In this review, the current advances in 3D dynamic cell culture approaches have been introduced, with their advantages and disadvantages being discussed in comparison to traditional 2D cell culture in static conditions.
Publisher: Wiley
Date: 02-2017
Publisher: Oxford University Press (OUP)
Date: 08-2019
Publisher: Elsevier BV
Date: 10-2021
Publisher: Springer Science and Business Media LLC
Date: 17-10-2017
Abstract: The activation of M1 macrophages can be achieved by stimulating them with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). However, M1 can be found under physiological conditions without any pathological stimuli. This study aimed to understand the involvement of RANKL-induced M1 macrophages in bone formation compared with pathologically induced macrophages. Fischer rats were used to investigate macrophage distribution in normal and injured femoral condyles in vivo . Bone marrow-derived macrophages (BMDMs) were activated with LPS+IFN-γ and RANKL to achieve M1 activation in vitro . Gene expression related to inflammation, osteoclastogenesis, angiogenesis, and migration was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS). Tissue macrophages showed distinct expression patterns at different bone regions. RANKL was found in close proximity to inducible nitric oxide synthase-positive (iNOS+) cells in vivo , suggesting an association between RANKL expression and iNOS+ cells, especially in trabecular bone. RANKL-induced macrophages showed a different cytokine secretion profile compared with pathologically induced macrophages. Both osteoclasts and M1 macrophages peaked on day 7 during bone healing. RANKL could trigger M1-like macrophages with properties that were different from those of LPS+IFN-γ-induced macrophages. These RANKL-activated M1 macrophages were actively involved in bone formation.
Publisher: American Chemical Society (ACS)
Date: 20-07-2020
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.ARCHORALBIO.2013.07.015
Abstract: Theaflavin (TF) from the black tea can react to human salivary proline-rich proteins (PRPs) to form stains on exposed dental surfaces. Here, we employed a model of protein igment film using TF and dephosphorylated bovine β-casein (Dβ-CN), which has an extended conformation, similar to that of salivary PRPs, on a sensor surface to assess the efficacy of cysteine proteases (CPs) including papain, stem bromelain, and ficin, on removing TF bound to Dβ-CN and the control TF readsorption on the residual substrate surfaces was also measured. The protein igment complex film was built by using a quartz crystal microbalance with dissipation (QCM-D). The efficacies of CPs were assessed by Boltzman equation model. The surface details were detected by grazing angle infrared spectroscopy spectra, atomic force microscopy images, and contact angles. The efficacy order of CPs on hydrolyzing protein igment complex film is ficin>papain>bromelain. The results from grazing angle infrared spectroscopy spectra, atomic force microscopy images, and contact angles demonstrated that TF bound on the Dβ-CN was effectively removed by the CPs, and the amount of TF readsorption on both the residual film of the Dβ-CN/TF and the Dβ-CN was markedly decreased after hydrolysis. This study indicates the potential application of the CPs for tooth stain removal and suggests that these enzymes are worthy of further investigation for use in oral healthcare.
Publisher: Spandidos Publications
Date: 03-03-2015
Abstract: The repair of bone defects that result from periodontal diseases remains a clinical challenge for periodontal therapy. β-tricalcium phosphate (β-TCP) ceramics are biodegradable inorganic bone substitutes with inorganic components that are similar to those of bone. Demineralized bone matrix (DBM) is an acid-extracted organic matrix derived from bone sources that consists of the collagen and matrix proteins of bone. A few studies have documented the effects of DBM on the proliferation and osteogenic differentiation of human periodontal ligament cells (hPDLCs). The aim of the present study was to investigate the effects of inorganic and organic elements of bone on the proliferation and osteogenic differentiation of hPDLCs using three-dimensional porous β-TCP ceramics and DBM with or without osteogenic inducers. Primary hPDLCs were isolated from human periodontal ligaments. The proliferation of the hPDLCs on the scaffolds in the growth culture medium was examined using a Cell-Counting kit-8 (CCK-8) and scanning electron microscopy (SEM). Alkaline phosphatase (ALP) activity and the osteogenic differentiation of the hPDLCs cultured on the β-TCP ceramics and DBM were examined in both the growth culture medium and osteogenic culture medium. Specific osteogenic differentiation markers were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). SEM images revealed that the cells on the β-TCP were spindle-shaped and much more spread out compared with the cells on the DBM surfaces. There were no significant differences observed in cell proliferation between the β-TCP ceramics and the DBM scaffolds. Compared with the cells that were cultured on β-TCP ceramics, the ALP activity, as well as the Runx2 and osteocalcin (OCN) mRNA levels in the hPDLCs cultured on DBM were significantly enhanced both in the growth culture medium and the osteogenic culture medium. The organic elements of bone may exhibit greater osteogenic differentiation effects on hPDLCs than the inorganic elements.
Publisher: American Chemical Society (ACS)
Date: 07-05-2018
Publisher: ACTAPRESS
Date: 2012
Publisher: American Chemical Society (ACS)
Date: 02-12-2019
DOI: 10.1021/ACS.NANOLETT.9B03777
Abstract: Although a variety of advanced sterilization materials and treatments have emerged, the complete elimination of bacterial infection, especially drug-resistant bacterial infection, remains an immense challenge. Here, we demonstrate the use of neutrophils loaded with photocatalytic nanoparticles to reduce bacterial infection. This method activates the immune system to achieve an anti-infection response. We prepared the photocatalytic nanoparticle-laden neutrophils in vivo through neutrophil phagocytosis. The resulting loaded cells retained the cell membrane functionality of the source cell, as well as the complete immune cell function of neutrophils, particularly the ability to recruit macrophages to the target area. Photocatalytic nanoparticle-laden neutrophils can target infection sites and release reactive oxygen species to induce the secretion of chemokines, leading to the targeted recruitment of macrophages and enhancing a powerful immune cascade. In a severe mouse infection model induced by pathogenic bacteria, small doses of photocatalytic nanoparticle-laden neutrophils showed a remarkable therapeutic effect by enhancing macrophage recruitment and the immune cascade.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.ACTBIO.2018.09.011
Abstract: Bone morphogenetic protein-2 (BMP-2) involved therapy is of great potential for bone regeneration. However, its clinical application is restricted due to the undesirable bioactivity and relevant complications in vivo. Immobilization of recombinant BMP-2 (rhBMP-2) is an efficient strategy to mimic natural microenvironment and retain its bioactivity. Herein, we present evidences indicating that osteoinductive capacity of rhBMP-2 can be regulated via variant immobilizing approaches. Three representative superficial immobilizing models were employed to fabricate rhBMP-2-immobilized surfaces including physical adsorption (Au/rhBMP-2), covalent grafting (rhBMP-2-SAM-Au) and heparin binding (Hep-SAM-Au/rhBMP-2) (SAM: self-assembled monolayer). Loading capacity, releasing behavior, osteogenic differentiation and signaling pathways involved, as well as the cellular recognition of rhBMP-2 under various immobilization modes were systematically investigated. As a result, disparate immobilizing approaches not only have effects on loading capacity, but also lead to disparity of osteoinduction at the same dosage. Notably, heparin could reinforce the recognition between rhBMP-2 and its receptors (BMPRs) whereas weaken its binding to its antagonist Noggin. Owing to this "selective" binding feature, the favorable osteoinduction and maximum ectopic bone formation can be achieved with the heparin-binding approach. In particular, manipulation of orientation-mediated BMP-2-cell recognition efficiency may be a potential target to design more therapeutic efficient rhBMP-2 delivery system. STATEMENT OF SIGNIFICANCE: Bone morphogenetic protein-2 (BMP-2) is crucial in bone regeneration. However, its clinical application is challenged due to its shorten half-life and supra-physiological dose associated complications. In this study, three representative superficial immobilizing patterns were fabricated through physical adsorption, covalent grafting and electrostatic interaction with heparin respectively. We provided evidences indicating an dose-dependent osteoinductive capacity of immobilized BMP-2. Further, a possible mechanism of rhBMP-2-cell recognition at the interface was presented, highlighting the superior effect of heparin on rhBMP-2 bioactivity. Finally, We proposed a dual mechanism of tuning the bioactivity of immobilized rhBMP-2 through surface immobilization approaches: regulation of the saturated loading capacity and orientation-mediated rhBMP-2-cell recognition. These results provide novel insights into designing criterion of efficient delivery vehicle for rhBMP-2.
Publisher: Quintessence Publishing
Date: 05-2014
DOI: 10.11607/JOMI.3195
Abstract: The purpose of this study was to identify retrospectively the predictors of implant survival when the flapless protocol was used in two private dental practices. The collected data were initially computer searched to identify the patients later, a hand search of patient records was carried out to identify all flapless implants consecutively inserted over the last 10 years. The demographic information gathered on statistical predictors included age, sex, periodontal and peri-implantitis status, smoking, details of implants inserted, implant locations, placement time after extraction, use of simultaneous guided hard and soft tissue regeneration procedures, loading protocols, type of prosthesis, and treatment outcomes (implant survival and complications). Excluded were any implants that required flaps or simultaneous guided hard and soft tissue regeneration procedures, and implants narrower than 3.25 mm. A total of 1,241 implants had been placed in 472 patients. Life table analysis indicated cumulative 5-year and 10-year implant survival rates of 97.9% and 96.5%, respectively. Most of the failed implants occurred in the posterior maxilla (54%) in type 4 bone (74.0%), and 55.0% of failed implants had been placed in smokers. Flapless dental implant surgery can yield an implant survival rate comparable to that reported in other studies using traditional flap techniques.
Publisher: Wiley
Date: 10-11-2011
DOI: 10.1111/J.1600-0501.2011.02341.X
Abstract: Simvastatin has been shown to enhance osseointegration of pure titanium implants in osteoporotic rats. This study aimed to evaluate the relationship between the serum level of bone formation markers and the osseointegration of pure titanium implants in osteoporotic rats treated with simvastatin. Fifty-four female Sprague-Dawley rats, aged 3 months, were randomly ided into three groups: Sham-operated group (SHAM n = 18), ovariectomized group (OVX n = 18), and ovariectomized with simvastatin treatment group (OVX + SIM n = 18). Fifty-six days after ovariectomy, screw-shaped titanium implants were inserted into the tibiae. Simvastatin was administered orally at 5 mg/kg each day after the placement of the implant in the OVX + SIM group. The animals were killed at either 28 or 84 days after implantation and the undecalcified tissue sections were processed for histological analysis. Total alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP) and bone Gla protein (BGP) were measured in all animal sera collected at the time of euthanasia and correlated with the histological assessment of osseointegration. The level of ALP in the OVX group was higher than the SHAM group at day 28, with no differences between the three groups at day 84. The level of BALP in the OVX + SIM group was significantly higher than both OVX and SHAM groups at days 28. Compared with day 28, the BALP level of all three groups showed a significant decrease at day 84. There were no significant differences in BGP levels between the three groups at day 28, but at day 84, the OVX + SIM group showed significantly higher levels than both the OVX and SHAM groups. There was a significant increase in BGP levels between days 28 and 84 in the OVX + SIM group. The serum bone marker levels correlated with the histological assessment showing reduced osseointegration in the OVX compared to the SHAM group which is subsequently reversed in the OVX + SIM group. The results from this study indicate that the serum level of bone formation markers, especially BALP and BGP, could be correlated with the degree of osseointegration around titanium implants in osteoporotic rats treated with simvastatin.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C7BM00869D
Abstract: Barrier membranes with nano-sized bioceramic coating can modulate the osteoimmune responses to stimulate osteogenesis.
Publisher: Wiley
Date: 18-04-2012
DOI: 10.1002/JBMR.1552
Publisher: SAGE Publications
Date: 08-06-2013
Abstract: The repair of articular cartilage typically involves the repair of cartilage–subchondral bone tissue defects. Although various bioactive materials have been used to repair bone defects, how these bioactive materials in subchondral bone defects influence the repair of autologous cartilage transplant remains unclear. The aim of this study was to investigate the effects of different subchondral biomaterial scaffolds on the repair of autologous cartilage transplant in a sheep model. Cylindrical cartilage–subchondral bone defects were created in the right femoral knee joint of each sheep. The subchondral bone defects were implanted with hydroxyapatite–β-tricalcium phosphate (HA–TCP), poly lactic-glycolic acid (PLGA)-HA–TCP dual-layered composite scaffolds (PLGA/HA–TCP scaffolds), or autologous bone chips. The autologous cartilage layer was placed on top of the subchondral materials. After 3 months, the effect of different subchondral scaffolds on the repair of autologous cartilage transplant was systematically studied by investigating the mechanical strength, structural integration, and histological responses. The results showed that the transplanted cartilage layer supported by HA–TCP scaffolds had better structural integration and higher mechanical strength than that supported by PLGA/HA–TCP scaffolds. Furthermore, HA–TCP-supported cartilage showed higher expression of acid mucosubstances and glycol-amino-glycan contents than that supported by PLGA/HA–TCP scaffolds. Our results suggested that the physicochemical properties, including the inherent mechanical strength and material chemistry of the scaffolds, play important roles in influencing the repair of autologous cartilage transplants. The study may provide useful information for the design and selection of proper subchondral biomaterials to support the repair of both subchondral bone and cartilage defects.
Publisher: Trans Tech Publications, Ltd.
Date: 02-2008
DOI: 10.4028/WWW.SCIENTIFIC.NET/AMR.32.215
Abstract: Cell-based therapy is one of the major potential therapeutic strategies for cardiovascular, neuronal and degenerative diseases in recent years. The aims of this study is to develop a novel biomimic polymeric materials which will facilitate the delivery cells, control cell bioactivities and enhance the focal integration of graft cells with host tissues. We synthesized a novel tri-block copolymer, methoxy-terminated poly (ethylene glycol) (MPEG)-polyL-lactide (PLLA)-polylysine (PLL) via sequential polymerization of PLLA onto MPEG, followed by ring opening polymerization of PLL onto the functionalized chain end. The triblock copolymer (5%) was then mixed with high molecular weight PLLA (95%) to form cell-delivery membranes. The spectra of copolymers were determined by NMR and ATR-FTIR spectroscopy. Human osteoblasts were used for testing biocompatibility and initial cellular reaction. It was noted that no cytotoxicity was detectable in our synthesized copolymers. Compared with pure PLLA and diblock copolymers, the triblock copolymers showed significantly better cell adhesion and proliferation. Interestingly we identified that cellular activity (attachment, proliferation and differentiation) could be regulated by the molecular weight and composition of the triblock copolymers. In conclusion controllable synthetic copolymers can be designed and synthesized to modulate cellular function in facilitating tissue repair and regeneration.
Publisher: Springer Science and Business Media LLC
Date: 03-10-2022
DOI: 10.1007/S10856-022-06693-0
Abstract: Repeat firing produces uncertainty about stabilizing lithium disilicate glass-ceramic (LDGC) material properties, even though prolonged holding time can enhance the mechanical property of LDGC during a single firing cycle. However, the effect of prolonged holding time and repeat firing on the mechanical property and microstructure of LDGC is not fully understood. In the present study, three groups of LDGC material were created: (i) extension of holding time (7 vs. 14 vs. 28 min) at 780–800 °C (ii) holding time extension (7 vs. 14 min) and dual sintering at 800–820 °C, respectively (iii) dual sintering with prolonged holding time (7 vs. 14 min) at 820–840 °C. The nano-indenter test revealed that prolonged holding time (14 and 28 min) promoted the enhancement of LDGC hardness and Young’s modulus. X-ray photoelectron spectroscopy, X-ray diffraction and Fourier transform infrared spectroscopy confirmed that prolonged holding time increased and stabilized LD phase in LDGC, as well as induced residual compressive stress. Scanning electron microscopy showed that prolonged holding time increased LD crystal grains homogeneously and facilitated LDGC to form dense interlocking structure without enlarging crystal size grains significantly. In contrast, LDGC that dual sintered alone at 820–840 °C possessed inferior mechanical properties, coupled with heterogeneous crystal phases, residual tensile stress, and melted crystals grains in the porous microstructure. Interestingly, these deteriorated properties of LDGC caused by dual sintering alone could be counteracted by prolonging the holding time. Nevertheless, the LDGC materials displayed an excellent biocompatibility throughout the study. This study identified that prolonged holding time during repeated firing cycles stabilized LD phase and crystal grain size of LDGC, thus enhanced the mechanical properties, which provided a new insight to extend the repeat fired restoration longevity of LDGC.
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.ACTBIO.2011.06.028
Abstract: Hyperthermia and local drug delivery have been proposed as potential therapeutic approaches for bone defects resulting from malignant bone tumors. The development of bioactive materials with magnetic and drug delivery properties may potentially meet this target. The aim of this study was to develop a multifunctional mesoporous bioactive glass (MBG) scaffold system for both hyperthermic and local drug delivery applications. To this end iron (Fe)-containing MBG (Fe-MBG) scaffolds with a hierarchical large pores structure (300-500 μm) and fingerprint-like mesopores (4.5 nm) have been prepared. The effects of Fe on the mesopore structure and physiochemical, magnetic, drug delivery and biological properties of MBG scaffolds have been systematically investigated. The results show that the morphology of the mesopores varied from straight channels to curved fingerprint-like channels after incorporation of Fe into MBG scaffolds. The magnetism of MBG scaffolds can be tailored by controlling the Fe content. Furthermore, the incorporation of Fe into mesoporous MBG glass scaffolds enhanced the mitochondrial activity and the expression of bone-related genes (ALP and OCN) in human bone marrow mesenchymal stem cells (BMSC) attached to the scaffolds. The Fe-MBG scaffolds obtained also possessed high specific surface areas and demonstrated sustained drug delivery. Thus Fe-MBG scaffolds are magnetic, degradable and bioactive. The multifunctionality of Fe-MBG scaffolds suggests that there is great potential for their use in the treatment and regeneration of large-bone defects caused by malignant bone tumors through a combination of hyperthermia, local drug delivery and osteoconductivity.
Publisher: Elsevier BV
Date: 07-1970
Publisher: Springer Science and Business Media LLC
Date: 18-08-2020
DOI: 10.1186/S13075-020-02290-0
Abstract: Cartilage matrix remodelling homeostasis is a crucial factor in maintaining cartilage integrity. Loss of cartilage integrity is a typical characteristic of osteoarthritis (OA). Strategies aimed at maintaining cartilage integrity have attracted considerable attention in the OA research field. Recently, a series of studies have suggested dual functions of microRNA-140 (miR-140) in cartilage matrix remodelling. Here, we discuss the significance of miR-140 in promoting cartilage formation and inhibiting degeneration. Additionally, we focused on the role of miR-140 in the chondrogenesis of mesenchymal stem cells (MSCs). Of note, we carefully reviewed recent advances in MSC exosomes for miRNA delivery in OA treatment.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.ACTBIO.2015.04.019
Abstract: Multifunctional bioactive materials with the ability to stimulate osteogenesis and angiogenesis of stem cells play an important role in the regeneration of bone defects. However, how to develop such biomaterials remains a significant challenge. In this study, we prepared mesoporous silica nanospheres (MSNs) with uniform sphere size (∼90 nm) and mesopores (∼2.7 nm), which could release silicon ions (Si) to stimulate the osteogenic differentiation of human bone marrow stromal cells (hBMSCs) via activating their ALP activity, bone-related gene and protein (OCN, RUNX2 and OPN) expression. Hypoxia-inducing therapeutic drug, dimethyloxaloylglycine (DMOG), was effectively loaded in the mesopores of MSNs (D-MSNs). The sustained release of DMOG from D-MSNs could stabilize HIF-1α and further stimulated the angiogenic differentiation of hBMSCs as indicated by the enhanced VEGF secretion and protein expression. Our study revealed that D-MSNs could combine the stimulatory effect on both osteogenic and angiogenic activity of hBMSCs. The potential mechanism of D-MSN-stimulated osteogenesis and angiogenesis was further elucidated by the supplementation of cell culture medium with pure Si ions and DMOG. Considering the easy handling characteristics of nanospheres, the prepared D-MSNs may be applied in the forms of injectable spheres for minimally invasive surgery, or MSNs olymer composite scaffolds for bone defect repair. The concept of delivering both stimulatory ions and functional drugs may offer a new strategy to construct a multifunctional biomaterial system for bone tissue regeneration.
Publisher: Informa UK Limited
Date: 06-2013
DOI: 10.2147/IJN.S44393
Publisher: MDPI AG
Date: 27-12-2022
DOI: 10.3390/BIOM13010049
Abstract: Osteocytes play an important role in bone metabolism. The interactions of osteocytes with the surrounding microenvironment can alter cellular and lacunar morphological changes. However, objective quantification of osteocyte lacunae is challenging due to their deep location in the bone matrix. This project established a novel method for the analytical study of osteocytes/lacunae, which was then used to evaluate the osteocyte morphological changes in diabetic pig mandibular bone. Eight miniature pigs were sourced, and diabetes was randomly induced in four animals using streptozotocin (STZ) administration. The mandibular tissues were collected and processed. The jawbone density was evaluated with micro-CT. Osteocyte lacunae were effectively acquired and identified using backscattered electron scanning microscopy (BSE). A significantly decreased osteocyte lacunae size was found in the diabetic group. Using the acid etching method, it was demonstrated that the area of osteocyte and lacunae, and the pericellular areas were both significantly reduced in the diabetes group. In conclusion, a standard and relatively reliable method for analyzing osteocyte/lacunae morphological changes under compromised conditions has been successfully established. This method demonstrates that diabetes can significantly decrease osteocyte/lacunae size in a pig’s mandibular cancellous bone.
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1016/J.ACTBIO.2007.10.006
Abstract: Regeneration of bone, cartilage and osteochondral tissues by tissue engineering has attracted intense attention due to its potential advantages over the traditional replacement of tissues with synthetic implants. Nevertheless, there is still a dearth of ideal or suitable scaffolds based on porous biomaterials, and the present study was undertaken to develop and evaluate a useful porous composite scaffold system. Here, hydroxyapatite (HA)/tricalcium phosphate (TCP) scaffolds (average pore size: 500 microm porosity: 87%) were prepared by a polyurethane foam replica method, followed by modification with infiltration and coating of poly(lactic-co-glycolic acid) (PLGA). The thermal shock resistance of the composite scaffolds was evaluated by measuring the compressive strength before and after quenching or freezing treatment. The porous structure (in terms of pore size, porosity and pore interconnectivity) of the composite scaffolds was examined. The penetration of the bone marrow stromal stem cells into the scaffolds and the attachment of the cells onto the scaffolds were also investigated. It was shown that the PLGA incorporation in the HA/TCP scaffolds significantly increased the compressive strength up to 660 kPa and the residual compressive strength after the freezing treatment decreased to 160 kPa, which was, however, sufficient for the scaffolds to withstand subsequent cell culture procedures and a freeze-drying process. On the other hand, the PLGA coating on the strut surfaces of the scaffolds was rather thin (<5 microm) and apparently porous, maintaining the high open porosity of the HA/TCP scaffolds, resulting in desirable migration and attachment of the bone marrow stromal stem cells, although a thicker PLGA coating would have imparted a higher compressive strength of the PLGA-coated porous HA/TCP composite scaffolds.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.ACTBIO.2019.01.006
Abstract: Exosomes are extracellular nanovesicles that play an important role in cellular communication. The modulatory effects of bone morphogenetic protein 2 (BMP2) on macrophages have encouraged the functionalization of scaffolds through the integration of the exosomes from the BMP2-stimulated macrophages to avoid ectopic bone formation and reduce adverse effects. To determine the functionality of exosomal nanocarriers from macrophages after BMP2 stimulation, we isolated the exosomes from Dulbecco's modified Eagle's medium (DMEM)- or BMP2-stimulated macrophages and evaluated their effects on osteogenesis. Morphological characterization of the exosomes derived from DMEM- or BMP2-treated macrophages revealed no significant differences, and the bone marrow-derived mesenchymal stromal cells showed similar cellular uptake patterns for both exosomes. In vitro study using BMP2/macrophage-derived exosomes indicated their beneficial effects on osteogenic differentiation. To improve the bio-functionality for titanium implants, BMP2/macrophage-derived exosomes were used to modify titanium nanotube implants to favor osteogenesis. The incorporation of BMP2/macrophage-derived exosomes dramatically increased the expression of early osteoblastic differentiation markers, alkaline phosphatase (ALP) and BMP2, indicative of the pro-osteogenic role of the titanium nanotubes incorporated with BMP2/macrophage-derived exosomes. The titanium nanotubes functionalized with BMP2/macrophage-derived exosomes activated autophagy during osteogenic differentiation. In conclusion, the exosome-integrated titanium nanotube may serve as an emerging functional material for bone regeneration. STATEMENT OF SIGNIFICANCE: The clinical application of bone morphogenetic protein 2 (BMP2) is often limited by its side effects. Exosomes are naturally secreted nanosized vesicles derived from cells and play an important role in intercellular communication. The contributions of this study include (1) the demonstration of the potential regulatory role of BMP2/macrophage-derived exosomes on the osteogenic differentiation of mesenchymal stromal cells (MSCs) (2) fabrication of titanium nanotubes incorporated with exosomes (3) new insights into the application of titanium nanotube-based materials for the safe use of BMP2.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8NR08381A
Abstract: Inflammatory reactions and the functionality of endothelial cells (ECs) on the surfaces of coronary stents are critical in the prevention of in-stent restenosis and subsequent neoatherosclerosis.
Publisher: American Chemical Society (ACS)
Date: 03-12-2018
Publisher: Wiley
Date: 07-02-2023
Abstract: For regeneration of highly vascularized and innervated tissues, like bone, simultaneous ingrowth of blood vessels and nerves is essential but largely neglected. To address this issue, a “pre‐angiogenic” cell‐laden scaffold with durable angiogenic functions is prepared according to the bioactivities of silicate bioceramics and the instructive effects of vascular cells on neurogenesis and bone repair. Compared with traditional cell‐free scaffolds, the prepared cell‐laden scaffolds printed with active cells and bioactive inks can support long‐term cell survival and growth for three weeks. The long‐lived scaffolds exhibited durable angiogenic capability both in vitro and in vivo. The pre‐angiogenic scaffolds can induce the neurogenetic differentiation of neural cells and the osteogenic differentiation of mesenchymal stem cells by the synergistic effects of released bioactive ions and the ability of vascular cells to attract neurons. The enhanced bone regeneration with both vascularization and innervation is attributed to these physiological functions of the pre‐angiogenic cell‐laden scaffolds, which is defined as “vascular‐innervated” bone regeneration. It is suggested that the concept of “vascular‐innervated scaffolds” may represent the future direction of biomaterials for complex tissue/organ regeneration.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.ACTBIO.2012.03.012
Abstract: The ultimate goal of periodontal tissue engineering is to produce predictable regeneration of alveolar bone, root cementum, and periodontal ligament, which are lost as a result of periodontal diseases. To achieve this goal, it is of great importance to develop novel bioactive materials which could stimulate the proliferation, differentiation and osteogenic/cementogenic gene expression of periodontal ligament cells (PDLCs) for periodontal regeneration. In this study, we synthesized novel Ca(7)Si(2)P(2)O(16) ceramic powders for the first time by the sol-gel method and investigated the biological performance of PDLCs after exposure to different concentrations of Ca(7)Si(2)P(2)O(16) extracts. The original extracts were prepared at 200 mg ml(-1) and further diluted with serum-free cell culture medium to obtain a series of diluted extracts (100, 50, 25, 12.5 and 6.25 mg ml(-1)). Proliferation, alkaline phosphatase (ALP) activity, Ca deposition, and osteogenesis/cementogenesis-related gene expression (ALP, Col I, Runx2 and CEMP1) were assayed for PDLCs on days 7 and 14. The results showed that the ionic products from Ca(7)Si(2)P(2)O(16) powders significantly stimulated the proliferation, ALP activity, Ca deposition and osteogenesis/cementogenesis-related gene expression of PDLCs. In addition, it was found that Ca(7)Si(2)P(2)O(16) powders had excellent apatite-mineralization ability in simulated body fluids. This study demonstrated that Ca(7)Si(2)P(2)O(16) powders with such a specific composition possess the ability to stimulate the PDLC proliferation and osteoblast/cemenoblast-like cell differentiation, indicating that they are a promising bioactive material for periodontal tissue regeneration application.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.ACTBIO.2013.05.014
Abstract: Polyvinylpyrrolidone-iodine (Povidone-iodine, PVP-I) is widely used as an antiseptic agent for lavation during joint surgery however, the biological effects of PVP-I on cells from joint tissue are unknown. This study examined the biocompatibility and biological effects of PVP-I on cells from joint tissue, with the aim of optimizing cell-scaffold based joint repair. Cells from joint tissue, including cartilage derived progenitor cells (CPC), subchondral bone derived osteoblast and bone marrow derived mesenchymal stem cells (BM-MSC) were isolated. The concentration-dependent effects of PVP-I on cell proliferation, migration and differentiation were evaluated. Additionally, the efficacy and mechanism of a PVP-I loaded bilayer collagen scaffold for osteochondral defect repair was investigated in a rabbit model. A micromolar concentration of PVP-I was found not to affect cell proliferation, CPC migration or extracellular matrix production. Interestingly, micromolar concentrations of PVP-I promote osteogenic differentiation of BM-MSC, as evidenced by up-regulation of RUNX2 and Osteocalcin gene expression, as well as increased mineralization on the three-dimensional scaffold. PVP-I treatment of collagen scaffolds significantly increased fibronectin binding onto the scaffold surface and collagen type I protein synthesis of cultured BM-MSC. Implantation of PVP-I treated collagen scaffolds into rabbit osteochondral defect significantly enhanced subchondral bone regeneration at 6 weeks post-surgery compared with the scaffold alone (subchondral bone histological score of 8.80±1.64 vs. 3.8±2.19, p<0.05). The biocompatibility and pro-osteogenic activity of PVP-I on the cells from joint tissue and the enhanced subchondral bone formation in PVP-I treated scaffolds would thus indicate the potential of PVP-I for osteochondral defect repair.
Publisher: Springer Science and Business Media LLC
Date: 13-09-2017
DOI: 10.1038/S41598-017-11844-3
Abstract: We demonstrate in this study the potential of near infrared (NIR) spectroscopy as a tool for monitoring progression of cartilage degeneration in an animal model. Osteoarthritic degeneration was artificially induced in one joint in laboratory rats, and the animals were sacrificed at four time points: 1, 2, 4, and 6 weeks (3 animals/week). NIR spectra were acquired from both (injured and intact) knees. Subsequently, the joint s les were subjected to histological evaluation and glycosaminoglycan (GAG) content analysis, to assess disease severity based on the Mankin scoring system and to determine proteoglycan loss, respectively. Multivariate spectral techniques were then employed for classification (principal component analysis and support vector machines) and prediction (partial least squares regression) of the s les’ Mankin scores and GAG content from their NIR spectra. Our results demonstrate that NIR spectroscopy is sensitive to degenerative changes in articular cartilage, and is capable of distinguishing between mild (weeks 1& Mankin =2) and advanced (weeks 4& Mankin = ) cartilage degeneration. In addition, the spectral data contains information that enables estimation of the tissue’s Mankin score (error = 12.6%, R 2 = 86.2%) and GAG content (error = 7.6%, R 2 = 95%). We conclude that NIR spectroscopy is a viable tool for assessing cartilage degeneration post-injury, such as, post-traumatic osteoarthritis.
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1JM12770E
Publisher: Hindawi Limited
Date: 12-07-2016
DOI: 10.1002/TERM.2190
Abstract: Blood clots (haematomas) that form immediately following a bone fracture have been shown to be vital for the subsequent healing process. During the clotting process, a number of factors can influence the fibrin clot structure, such as fibrin polymerization, growth factor binding, cellular infiltration (including platelet retraction), protein concentrations and cytokines. The modulation of the fibrin clot structure within the fracture site has important clinical implications and could result in the development of multifunctional scaffolds that mimic the natural structure of a haematoma. Artificial haematoma structures such as these can be created from the patient's own blood and can therefore act as an ideal bone defect filling material for potential clinical application to accelerate bone regeneration. Copyright © 2016 John Wiley & Sons, Ltd.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0BM00450B
Abstract: LCS scaffolds promoted chondrocyte maturation by inducing M2 macrophage polarization.
Publisher: SAGE Publications
Date: 2004
DOI: 10.3727/000000004772664851
Abstract: The use of extracellular matrix materials as scaffolds for the repair and regeneration of tissues is receiving increased attention. The current study was undertaken to test whether extracellular matrix formed by osteoblasts in vitro could be used as a scaffold for osteoblast transplantation and induce new bone formation in critical size osseous defects in vivo. Human osteoblasts derived from alveolar bone were cultured in six-well plates until confluent and then in mineralization media for a further period of 3 weeks to form an osteoblast–mineralized matrix complex. Histologically, at this time point a tissue structure with a “connective tissue”-like morphology was formed. Type I collagen was the major extracellular component present and appeared to determine the matrix macrostructure. Other bone-related proteins such as alkaline phosphatase (ALP), bone morphogenetic protein (BMP)-2 and -4, bone sialoprotein (BSP), osteopontin (OPN), and osteocalcin (OCN) also accumulated in the matrix. The osteoblasts embedded in this matrix expressed mRNAs for these bone-related proteins very strongly. Nodules of calcification were detected in the matrix and there was a correlation between calcification and the distribution of BSP and OPN. When this matrix was transplanted into a critical size bone defect in skulls of immunodeficient mice (SCID), new bone formation occurred. Furthermore, the cells inside the matrix survived and proliferated in the recipient sites, and were traceable by the human-specific Alu gene sequence using in situ hybridization. It was found that bone-forming cells differentiated from both transplanted human osteoblasts and activated endogenous mesenchymal cells. This study indicates that a mineralized matrix, formed by human osteoblasts in vitro, can be used as a scaffold for osteoblast transplantation, which subsequently can induce new bone formation.
Publisher: American Chemical Society (ACS)
Date: 19-11-2018
Publisher: CRC Press
Date: 22-03-2013
DOI: 10.1201/B13926
Publisher: MDPI AG
Date: 30-06-2023
DOI: 10.3390/BIOM13071062
Abstract: Hydrogels have been widely applied to the fabrication of tissue engineering scaffolds via three-dimensional (3D) bioprinting because of their extracellular matrix-like properties, capacity for living cell encapsulation, and shapeable customization depending on the defect shape. However, the current hydrogel scaffolds show limited regeneration activity, especially in the application of periodontal tissue regeneration. In this study, we attempted to develop a novel multi-component hydrogel that possesses good biological activity, can wrap living cells for 3D bioprinting and can regenerate periodontal soft and hard tissue. The multi-component hydrogel consisted of gelatin methacryloyl (GelMA), sodium alginate (SA) and bioactive glass microsphere (BGM), which was first processed into hydrogel scaffolds by cell-free 3D printing to evaluate its printability and in vitro biological performances. The cell-free 3D-printed scaffolds showed uniform porous structures and good swelling capability. The BGM-loaded scaffold exhibited good biocompatibility, enhanced osteogenic differentiation, apatite formation abilities and desired mechanical strength. The composite hydrogel was further applied as a bio-ink to load with mouse bone marrow mesenchymal stem cells (mBMSCs) and growth factors (BMP2 and PDGF) for the fabrication of a scaffold for periodontal tissue regeneration. The cell wrapped in the hydrogel still maintained good cellular vitality after 3D bioprinting and showed enhanced osteogenic differentiation and soft tissue repair capabilities in BMP2- and PDGF-loaded scaffolds. It was noted that after transplantation of the cell- and growth factor-laden scaffolds in Beagle dog periodontal defects, significant regeneration of gingival tissue, periodontal ligament, and alveolar bone was detected. Importantly, a reconstructed periodontal structure was established in the treatment group eight weeks post-transplantation of the scaffolds containing the cell and growth factors. In conclusion, we developed a bioactive composite bio-ink for the fabrication of scaffolds applicable for the reconstruction and regeneration of periodontal tissue defects.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Wiley
Date: 19-08-2009
DOI: 10.1002/JCB.22312
Abstract: This study aimed to determine the cellular aging of osteophyte-derived mesenchymal cells (oMSCs) in comparison to patient-matched bone marrow stromal cells (bMSCs). Extensive expansion of the cell cultures was performed and early and late passage cells (passages 4 and 9, respectively) were used to study signs of cellular aging, telomere length, telomerase activity, and cell-cycle-related gene expression. Our results showed that cellular aging was more prominent in bMSCs than in oMSCs, and that oMSCs had longer telomere length in late passages compared with bMSCs, although there was no significant difference in telomere lengths in the early passages in either cell type. Telomerase activity was detectable only in early passage oMSCs and not in bMSCs. In osteophyte tissues telomerase-positive cells were found to be located perivascularly and were Stro-1 positive. Fifteen cell-cycle regulator genes were investigated and only three genes (APC, CCND2, and BMP2) were differentially expressed between bMSC and oMSC. Our results indicate that oMSCs retain a level of telomerase activity in vitro, which may account for the relatively greater longevity of these cells, compared with bMSCs, by preventing replicative senescence.
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.BIOMATERIALS.2019.03.039
Abstract: The regeneration of lost periodontal apparatus in periodontitis treatment remains a clinical challenge due to the limited regenerative capacity of cementum, periodontal ligament and alveolar bone in periodontitis condition. For periodontal tissue regeneration, it is essential to regulate the inflammatory response and the subsequent differentiation of periodontal cells under the condition due to the infectious nature of the disease. In this study, it was noted that 45 nm gold nanoparticles (AuNPs) could exhibit significant anti-inflammatory effect and improve the periodontal inflammatory microenvironment via regulating inflammatory and regenerative cytokine production and modulating macrophage polarization, subsequently affect the differentiation of human periodontal ligament cells (hPDLCs). With the addition of direct effects of AuNPs on hPDLCs, the periodontal tissue differentiation capacity of hPDLCs in LPS-activated inflammatory macrophage-hPDLCs coculture system was significantly enhanced by the interaction between AuNPs-conditioned macrophage and AuNPs-stimulated hPDLCs. The potential therapeutic application of AuNPs in periodontal tissue regeneration and periodontitis treatment was investigated using both rat fenestration and ligature-induced periodontitis models. It was found that the treatment of 45 AuNPs showed significantly increased newly-formed periodontal attachment, bone and cementum in periodontal defect and less tissue destruction in the progression of periodontitis. This study demonstrated that 45 nm AuNPs could not only directly modulate hPDLCs, but also regulate the early inflammatory response of periodontal tissues via the regulation of macrophage phenotypes, therefore, generate a microenvironment with constraint inflammatory cytokine levels and reparative cytokines such as bone morphogenetic protein-2 (BMP-2), leading to PDLC differentiation, periodontal tissue regeneration and the prevention of periodontitis progression.
Publisher: Elsevier
Date: 2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7NR00347A
Abstract: Current major obstacles for translating the nanoparticle (NP) morphology-related function into therapeutic purposes come from the challenges in understanding the mechanisms that determine cell lineage commitment and constructing a NP-based 3D functional structure, and few studies have successfully demonstrated clear evidence of regulating in vivo tissue regeneration by NP morphology so far. Here, we show that nanoparticle geometry can be harnessed to mediate bone regeneration in a rat cranial defect model. We successfully synthesized hydroxyapatite NPs with well-defined morphologies using a modified liquid-solution-solid (LSS) method. The NPs showed differential effects on stem cell behaviors such as particle uptake, autophagy activation and osteogenic differentiation. By integrating nanoparticles within gelatin, we achieved 3D scaffolds with uniformly-distributed nano-topologies which, can mediate in vivo osteogenesis through stimulation of autophagy, with spherical particles demonstrating the most robust bone formation capacity compared to other NPs. Our current work proposes a morphology-dependent effect of NPs on vascularization and bone formation and provides an innovative and feasible strategy for bone regenerative therapies.
No related grants have been discovered for Yin Xiao.