ORCID Profile
0000-0001-9757-7735
Current Organisations
University of Queensland
,
Queensland University of Technology
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
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: Mary Ann Liebert Inc
Date: 07-2023
Publisher: Spandidos Publications
Date: 31-10-2016
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: 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: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2BM01528E
Abstract: Pink1/Parkin-mediated mitophagy is required for micro/nano-modified titanium implants to accelerate osseointegration and the small GTPase Rab7 is essential for this mitophagy pathway.
Publisher: Wiley
Date: 16-01-2021
DOI: 10.1111/ODI.13753
Abstract: In this study, we attempted to define the precise window of time for molar root elongation using a gain‐of‐function mutation of β‐catenin model. Both the control and constitutively activated β‐catenin (CA‐β‐cat) mice received a one‐time tamoxifen administration (for activation of β‐catenin at newborn, postnatal day 3, or 5, or 7, or 9) and were harvested at the same stage of P21. Multiple approaches were used to define the window of time of postnatal tooth root formation. In the early activation groups (tamoxifen induction at newborn, or P3 or P5), there was a lack of molar root elongation in the CA‐β‐cat mice. When induced at P7, the root length was slightly reduced at P21. However, the root length was essentially the same as that in the control when β‐cat activated at P9. This study indicates that root elongation occurs in a narrow time of window, which is highly sensitive to a change of β‐catenin levels. Molecular studies showed a drastic decrease in the levels of nuclear factor I‐C (NFIC) and osterix (OSX), plus sharp reductions of odontoblast differentiation markers, including Nestin, dentin sialoprotein (DSP), and dentin matrix protein 1 (DMP1) at both mRNA and protein levels. Murine molar root elongation is precisely regulated by the Wnt/β‐catenin signaling within a narrow window of time (newborn to day 5).
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: 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: 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: 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: Informa UK Limited
Date: 12-01-2017
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: 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: 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: 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: 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: Frontiers Media SA
Date: 15-07-2021
DOI: 10.3389/FMATS.2021.698915
Abstract: Large segmental bone loss and bone resection due to trauma and/or the presence of tumors and cysts often results in a delay in healing or non-union. Currently, the bone autograft is the most frequently used strategy to manage large bone loss. Nevertheless, autograft harvesting has limitations, namely sourcing of autograft material, the requirement of an invasive procedure, and susceptibility to infection. These disadvantages can result in complications and the development of a bone substitute materials offers a potential alternative to overcome these shortcomings. Among the biomaterials under consideration to date, beta-tricalcium phosphate (β-TCP) has emerged as a promising material for bone regeneration applications due to its osteoconductivity and osteoinductivity properties as well as its superior degradation in vivo. However, current evidence suggests the use β-TCP can in fact delay bone healing and mechanisms for this observation are yet to be comprehensively investigated. In this review, we introduce the broad application of β-TCP in tissue engineering and discuss the different approaches that β-TCP scaffolds are customized, including physical modification (e.g., pore size, porosity and roughness) and the incorporation of metal ions, other materials (e.g., bioactive glass) and stem cells (e.g., mesenchymal stem cells). 3D and 4D printed β-TCP-based scaffolds have also been reviewed. We subsequently discuss how β-TCP can regulate osteogenic processes to aid bone repair/healing, namely osteogenic differentiation of mesenchymal stem cells, formation of blood vessels, release of angiogenic growth factors, and blood clot formation. By way of this review, a deeper understanding of the basic mechanisms of β-TCP for bone repair will be achieved which will aid in the optimization of strategies to promote bone repair and regeneration.
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: 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: 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: 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: 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: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2NR01998A
Abstract: Management of antibiotic-resistant bacteria-induced skin infections for rapid healing remains a critical clinical challenge.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/893479
Abstract: The magnetic Fe-MBG/C composite scaffolds with enhanced mechanical strength and multifunctionality have been successfully prepared. The study showed that the Fe-MBG/C composite scaffolds with the porosity of ca. 80% had interconnected macropores (200–500 µm) and mesopores (3.7–4.4 nm) and significantly enhanced the compressive strength compared to the pure MBG scaffolds. Importantly, the Fe-MBG/C composite scaffolds exhibited good bioactivity and sustained drug release property. At the same time, the Fe-MBG/C composite scaffolds could generate heat to raise the temperature of surrounding environment in an alternating magnetic field due to their superparamagnetic behavior. Therefore, the magnetic Fe-MBG/C composite scaffolds could form a multifunctional platform with bone regeneration, magnetic hyperthermia, and local drug delivery and have more potential for use in the regeneration of the critical-sized bone defects caused by bone tumors.
Publisher: Mary Ann Liebert Inc
Date: 06-2023
Publisher: Elsevier
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 11-2015
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: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C5BM00534E
Abstract: A bifunctional Ca–Mg–Si bioceramic induces osteogenic differentiation of gingival fibroblasts and inhibits plaque biofilm formation.
Publisher: Oxford University Press (OUP)
Date: 08-2019
Publisher: Elsevier BV
Date: 07-2021
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: 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: 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: OMICS Publishing Group
Date: 2015
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: 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: 07-1970
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: 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: 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: Mary Ann Liebert Inc
Date: 04-2018
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: 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: Mary Ann Liebert Inc
Date: 02-2019
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: Wiley
Date: 27-05-2021
DOI: 10.1111/JCPE.13486
Abstract: To characterize gingival metabolome in high‐fat diet (HFD)‐induced obesity in mice with/without periodontitis. HFD‐induced obesity mouse model was established by 16‐week feeding, and a lean control group was fed with low‐fat diet ( n = 21/group). Both models were induced for periodontitis on the left sides by molar ligation for 10 days, whereas the right sides were used as controls. Gingival metabolome and arginine metabolism were analysed by non‐targeted/targeted liquid chromatography–mass spectrometry. Of 2247 reference features, presence of periodontitis altered 165 in lean versus 885 in HFD mice and HFD altered 525 in absence versus 1435 in presence of periodontitis. Compared with healthy condition, periodontitis and HFD had distinct effects on gingival metabolome. Metabolomic impacts of periodontitis were generally greater in HFD mice versus lean controls. K‐medoids clustering showed that HFD lified the impacts of periodontitis on gingival metabolome in both intensity and extensity. Ten metabolic pathways were enriched, including 2 specific to periodontitis, 5 specific to HFD and 3 shared ones. Targeted validation on arginine metabolism confirmed the additive effects between HFD and periodontitis. The obese population consuming excessive HFD display lified metabolic response to periodontitis, presenting a metabolic susceptibility to exacerbated periodontal destruction.
Publisher: Mary Ann Liebert Inc
Date: 04-1970
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2CS00315E
Abstract: This tutorial review presents an overview of the emerging metal–organic framework glass nanocomposite materials with special emphasis on demonstrating configuration, fabrication, and interfacial engineering techniques.
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: 08-2012
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2NR06149J
Abstract: This review discusses the important role of immune cells in the management of periodontitis and the nanotherapeutic methods for immunoregulated periodontal tissue regeneration.
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: 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: 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: Wiley
Date: 15-05-2009
DOI: 10.1111/J.1600-0528.2009.00461.X
Abstract: The objectives of this study were to describe root caries patterns of Chinese adults and to analyze the effect of selected demographic and socioeconomic factors on these patterns. A total s le of 1080 residents aged 35-44-years-old and 1080 residents aged 65-74-years-old from three urban and three rural survey sites in Hubei Province participated in both an oral health interview and a clinical oral health examination. Root surface caries prevalence rates were 13.1% in the middle-aged group and 43.9% in the elderly group. The mean number of teeth affected by caries in the middle-aged group was reported at 0.21 and 1.0 in the elderly group. Mean Root Caries Index (RCI) scores of the middle-aged were reported at 6.29 and elderly subjects were reported at 11.95. Elderly people living in rural areas reported a higher RCI score (13.24) than those living in urban areas (10.70). A significantly higher frequency of root surface caries was observed in elderly participants (P < 0.001, OR = 3.80) and ethnic minorities (P < 0.001, OR = 1.93). In addition, smokers, nontea drinkers, and those with an annual household income of 10,000 yuan or less tended to have higher caries prevalence. RCI figures for the different tooth types ranged from 1% to 16%, indicating a wide variation in attack rates. In conclusion, our study suggests that root surface caries occurrence is high among the Chinese adult population, especially older adults. With an increasing number of retained teeth in both middle-aged and elderly people, root caries is a growing disease in the People's Republic of China which deserves more attention in future research.
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2JM30566F
Publisher: Frontiers Media SA
Date: 25-06-2019
Publisher: Springer Singapore
Date: 2020
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: MDPI AG
Date: 21-06-2016
DOI: 10.3390/IJMS17060977
Publisher: Informa UK Limited
Date: 04-2020
DOI: 10.2147/IJN.S238005
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.
Start Date: 2019
End Date: 2023
Funder: Australian Research Council
View Funded Activity