ORCID Profile
0000-0002-5227-9352
Current Organisations
Griffith University
,
Queensland University of Technology
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Publisher: Elsevier BV
Date: 07-2012
DOI: 10.1016/J.BIOCEL.2012.04.003
Abstract: Osteoclasts, bone-specialized multinucleated cells, are responsible for bone destructive diseases such as osteoporosis, periodontitis, and rheumatoid arthritis. Natural plant-derived products have received substantial attention given their potential therapeutic and preventive activities against human diseases. In the present study, we investigated the effects of isoliquiritigenin (ISL), a natural flavonoid isolated from licorice, on receptor activator of nuclear factor-κB ligand (RANKL)-induced in vitro osteoclastogenesis and inflammation-mediated bone destruction in vivo. We observed that ISL dose-dependently inhibited RANKL-induced osteoclast formation from RAW 264.7 and primary mouse bone marrow-derived macrophages (BMMs), as well as decreased the extent of lacunar resorption. Specifically, ISL targeted RANKL-induced osteoclastogenesis and F-actin rings formation at an early stage. The RANKL-stimulated mRNA expression of osteoclast-related genes and transcription factors were also diminished by ISL. Mechanistically, ISL blocked the RANKL-triggered RANK-TRAF6 association, phosphorylation of mitogen-activated protein kinases (MAPKs), inhibitor of κBα (IκBα) phosphorylation and degradation, nuclear factor-κB (NF-κB) p65 nuclear translocation, as well as activator protein (AP)-1 activation. ISL almost abrogated the nuclear factor of activated T cells (NFATc1) expression and inhibited its nuclear translocation specifically in pre-osteoclasts. Furthermore, the ectopic introduction of NFATc1 into osteoclast precursors almost reversed the ISL-elicited anti-osteoclastogenic effects. Consistent with the in vitro results, administration of ISL prevented inflammatory bone loss in mice by attenuating osteoclast activity. Taken together, our results demonstrated that ISL suppresses RANKL-induced osteoclastogenesis and inflammatory bone loss via RANK-TRAF6, MAPK, IκBα/NF-κB, and AP-1 signaling pathways. Therefore, ISL may be considered as a novel therapeutic and/or preventive strategy against lytic bone diseases.
Publisher: Elsevier BV
Date: 10-2022
Publisher: Informa UK Limited
Date: 13-10-2022
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: Mary Ann Liebert Inc
Date: 12-2022
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: 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: Frontiers Media SA
Date: 23-07-2019
Publisher: Springer Science and Business Media LLC
Date: 22-08-2022
DOI: 10.1186/S13036-022-00301-Z
Abstract: Polylactic acid (PLA) is a versatile and biodegradable scaffold widely used in biomedical fields to repair tissue defects. Exosomes derived from mesenchymal stem cells (MSCs) are nano-sized extracellular vesicles, which play an important role in tissue engineering in recent years. The primary focus of this study was to develop a bioactive 3D PLA scaffold using exosome-based strategy to improve its osteogenic and immunoregulatory potential. We firstly successfully isolated MSC-derived exosomes (MSC-Exo). Morphological analysis revealed that MSC-Exo exhibits a typical cup-shaped morphology with high expression of exosomal marker CD63. MSC-Exo internalization into recipient cells were also investigated using flow cytometry and confocal laser scanning microscopy. Porous 3D PLA scaffold coated MSC-Exo were used for immunoregulatory and osteogenic testing. Exosomes released from 3D PLA scaffold were validated in RAW264.7 and hBMSCs. The cell proliferation and live/dead assay indicated high biocompatibility for PLA-Exo scaffold. Additionally, PLA-Exo scaffold could reduce the pro-inflammatory marker expression and reactive oxygen species (ROS) production, indicating potential immunoregulatory potential. It is also confirmed that PLA-Exo scaffold could potentiate osteogenic differentiation in the osteogenesis assay. In conclusion, our results demonstrate this bioactive 3D-printed PLA scaffolds with MSC-Exo modification holds immunoregulatory potential and favor osteogenic differentiation, thus having potential applications in bone tissue regeneration.
Publisher: Mary Ann Liebert Inc
Date: 30-04-2021
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: 16-08-2022
Abstract: Key Laboratory for Ultrafine Materials of Ministry of Education Centre for Biomedical Technologies Current tissue engineering technology aims to achieve the regeneration of human tissues, which integrates the key factors such as scaffolds, cells and biomolecules. Among these key factors, the development of high‐performance scaffolds is the basis for the success of tissue engineering strategies. In the past decades, hydrogel scaffolds have been developed rapidly and widely used in biomedical field, however, their drawbacks have also been revealed, which shows that a single hydrogel scaffold cannot meet the excellent performance required in the field of tissue engineering. Recently, microspheres have been further engineered to fabricate structurally and functionally reliable artificial three‐dimensional scaffolds of desired shape with enhanced specific biological functions. Therefore, the effective combination of hydrogel and microspheres can facilitate the development of high‐performance scaffolds for tissue engineering and further fine‐tuning the composite structure, which is expected to solve the dilemma faced by a single scaffold. In this review paper, we systematically summurized the type and preparation method for synthesis of hydrogel and microsphere materials commonly used in developing microsphere‐containing hydrogel scaffolds. We then reviewed the broad application of these hybrid scaffolds in various fields of tissue engineering, followed by a summary and perspective on future directions.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.BBRC.2019.03.132
Abstract: Traditional treatments for bone repair with allografts and autografts are limited by the source of bone substitutes. Bone tissue engineering via a cell-based bone tissue scaffold is a new strategy for treatment against large bone defects with many advantages, such as the accessibility of biomaterials, good biocompatibility and osteoconductivity however, the inflammatory immune response is still an issue that impacts osteogenesis. Sphingosine 1-phosphate (S1P) is a cell-derived sphingolipid that can mediate cell proliferation, immunoregulation and bone regeneration. We hypothesised that coating S1P on a β-Tricalcium phosphate (β-TCP) scaffold could regulate the immune response and increase osteogenesis. We tested the immunoregulation capability on macrophages and the osteogenic capability on rat bone marrow stromal cells of the coated scaffolds, which showed good biocompatibility. Additionally, the coated scaffolds exhibited dose-dependent inhibition of inflammatory-related gene expression. A high concentration of S1P (0.5 μM) upregulated osteogenic-related gene expression of OPN, OCN and RUNX2, which also significantly increased the alkaline phosphatase activity, as compared with the control group. In conclusion, S1P coated β-TCP scaffold could inhibit inflammation and promote bone regeneration.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0BM00867B
Abstract: Ultrasmall IONP-decorated graphene oxide (GO) nanohybrids present T 1 / T 2 dual MRI imaging-guided photothermal-chemo combined anticancer theranostics efficacy.
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.ACTBIO.2014.08.014
Abstract: Bioactive materials play an important role in facilitating dental pulp repair when living dental pulp is exposed after injuries. Mineral trioxide aggregate is the currently recommended material of choice for pulp repair procedures though has several disadvantages, especially the inconvenience of handling. Little information is yet available about the early events and molecular mechanisms involved in bioceramic-mediated dental pulp repair. We aimed to characterize and determine the apatite-forming ability of the novel ready-to-use nanoparticulate bioceramic iRoot BP Plus, and investigate its effects on the in vitro recruitment of human dental pulp stem cells (DPSCs), as well as its capacity to induce dentin bridge formation in an in vivo model of pulp repair. It was found that iRoot BP Plus was nanosized and had excellent apatite-forming ability in vitro. Treatment with iRoot BP Plus extracts promoted the adhesion, migration and attachment of DPSCs, and optimized focal adhesion formation (Vinculin, p-Paxillin and p-Focal adhesion kinase) and stress fibre assembly. Consistent with the in vitro results, we observed the formation of a homogeneous dentin bridge and the expression of odontogenic (dentin sialoprotein, dentin matrix protein 1) and focal adhesion molecules (Vinculin, p-Paxillin) at the injury site of pulp repair model by iRoot BP Plus. Our findings provide valuable insights into the mechanism of bioceramic-mediated dental pulp repair, and the novel revolutionary ready-to-use nanoparticulate bioceramic paste shows promising therapeutic potential in dental pulp repair application.
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: Elsevier BV
Date: 08-2020
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: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8RA02072H
Abstract: Microsphere based drug delivery systems show great advantages for tissue engineering.
Publisher: Elsevier BV
Date: 03-2023
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: Informa UK Limited
Date: 10-2022
DOI: 10.2147/IJN.S375999
Publisher: Wiley
Date: 11-08-2022
Abstract: Although immune checkpoint inhibitors (ICIs) have been widely applied to treat non‐small cell lung cancer (NSCLC), a significant proportion of patients, especially those with spinal metastasis (NSCLC‐SM), are insensitive to anti‐programmed death 1 (PD‐1) rogrammed death ligand 1 (PD‐L1) ICIs. A drug delivery nano‐controller of PD‐L1 that targets NSCLC‐SM can solve this problem, however, none have been developed to date. In this study, it is shown that integrin β 3 ( β 3‐int) is strongly upregulated in NSCLC‐SM. Its inhibitor RGDyK promotes PD‐L1 ubiquitination, indicating the potential application of RGDyK as a new PD‐L1 inhibitor in nano‐controller and a targeting peptide for NSCLC‐SM treatment. According to the synergistic effect of photodynamic therapy and ICIs on T‐cell activation through the release of tumor antigens, RGDyK‐modified and zinc protoporphyrin (ZnPP)‐loaded mesoporous silicon nanoparticles (ZnPP@MSN‐RGDyK) are fabricated. The ZnPP@MSN‐RGDyK nanoparticles precisely target β 3‐int to inhibit PD‐L1, exhibiting high photodynamic therapy efficiency, and excellent immunotherapeutic effects in an NSCLC‐SM mouse model. Collectively, the findings indicate that ZnPP@MSN‐RGDyK is a promising immunotherapeutic agent for treating NSCLC‐SM.
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: Frontiers Media SA
Date: 08-02-2021
DOI: 10.3389/FMATS.2020.622669
Abstract: The development of scaffolds with bone-mimicking compositions, hierarchical structure, and bone-matchable mechanical properties may offer a novel route for the achievement of effective bone regeneration. Although bioactive glasses have been widely utilized for bone regeneration at the clinical level, their brittleness and uncontrolled pore structure limit further applications. Herein, this study aims to develop a kind of bioactive scaffold with a macroporous/microporous/mesoporous structure via impregnating a sponge template with mesoporous bioactive glass (MBG) sol, followed by sponge template removal. In order to improve the mechanical properties and stability of the MBG scaffolds, desaminotyrosyl ethyl tyrosine polycarbonates (PDTEC), a biodegradable polymer which does not induce acid side-effects caused by conventional polylactide, was selected to decorate the resulting hierarchical scaffolds through a surface coating approach. The PDTEC functionalization endowed the scaffolds with improved mechanical strength matching the bearable range of trabecular bone (2–12 MPa). Meanwhile, the relative neutral pH value was maintained during their degradation process. In vitro studies demonstrated that the PDTEC accelerated the biomineralization of the scaffolds, and promoted the attachment and proliferation, holding high promise for bone regeneration.
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: 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: Informa UK Limited
Date: 03-07-2022
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: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5TB00894H
Abstract: A proposed schematic model of autophagy involvement in resin monomer-initiated toxicity of dental mesenchymal cells and as a novel therapeutic target of NAC.
Publisher: Mary Ann Liebert Inc
Date: 11-2022
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.JOEN.2013.09.033
Abstract: Interleukin (IL)-17(+) T-helper (Th17) cells and Foxp3(+) regulatory T (Treg) cells are CD4(+) T-helper cells with reciprocal functions in immunology and bone metabolism. The present study aimed to investigate the expression dynamics of Th17 and Treg cells in rat periapical lesions as well as their correlation with bone resorption. Experimental pulp exposures were made in the lower first molars of 28 Wistar rats to induce periapical lesions. Rats were killed on days 0, 7, 21, and 35. Mandibles were prepared for micro-computed tomography scanning, histologic observation, immunohistochemistry, enzyme histochemistry, and double immunofluorescence analysis. Through 3-dimensional and 2-dimensional measurements, the volume and area of periapical lesions visibly increased from day 7 to day 21 and then expanded slowly between days 21 and 35. IL-17-positive cells markedly increased from day 7 to day 35. However, Foxp3-positive cells remained at low levels until day 21 and then dramatically increased by day 35. The IL-17(+)/Foxp3(+) ratio and number of osteoclasts simultaneously increased from day 7 to day 21 and then decreased on day 35. Finally, the distinct distribution of CD4(+)/IL-17(+) Th17 and CD4(+)/Foxp3(+) Treg cells was observed on days 7 and 35. Our findings imply the imbalance of IL-17(+) T cell and Foxp3(+) Treg cell dynamics in induced periapical lesions, which may play an important role in periapical lesion progression.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0TB00958J
Abstract: Nanohybrids containing amino acid are doped into biodegradable nanofibrous membranes, which improves the cell affinity, the migration and growth of fibroblasts, and the neovascularization capacity, comprehensively accelerating a rapid wound healing.
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: Informa UK Limited
Date: 08-03-2023
Publisher: Wiley
Date: 05-02-2023
Abstract: Biodegradable materials are pivotal in the biomedical field, where how to precisely control their structure and performance is critical for their translational application. In this study, poly(L‐lactide‐ b ‐ ε ‐caprolactone) block copolymers (bPLCL) with well‐defined segment structure are obtained by a first synthesis of poly(ε‐caprolactone) soft block, followed by ring opening polymerization of lactide to form poly(L‐lactide acid) hard block. The pre‐polymerization allows for fabrication of bPLCL with the definite compositions of soft/hard segment while preserving the in idual segment of their special soft or hard segment. These priorities make the bPLCL afford biodegradable polymer with better mechanical and biodegradable controllability than the random poly(L‐lactide‐co‐ε‐caprolactone) (rPLCL) synthesized via traditional one‐pot polymerization. 10 mol% ε ‐caprolactone introduction can result in a formation of an elastic polymer with elongation at break of 286.15% ± 55.23%. Also, bPLCL preserves the unique crystalline structure of the soft and hard segments to present a more sustainable biodegradability than the rPLCL. The combinative merits make the pre‐polymerization technique a promising strategy for a scalable production of PLCL materials for potential biomedical application.
Publisher: Wiley
Date: 23-03-2022
Abstract: Control over soft‐to‐hard tissue interfaces is attracting intensive worldwide research efforts. Herein, a bioactive film‐guided soft–hard interface design (SHID) for multi‐tissue integrative regeneration is shown. Briefly, a soft bioactive film with good elasticity matchable to native ligament tissue, is incorporated with bone‐mimic components (calcium phosphate cement, CPC) to partially endow the soft‐film with hard‐tissue mimicking feature. The hybrid film is elegantly compounded with a clinical artificial ligament to act as a buffer zone to bridge the soft (ligament) and hard tissues (bone). Moreover, the bioactive film‐decorated ligament can be rolled into a 3D bio‐instructive implant with spatial‐controllable distribution of CPC bioactive motifs. CPC then promotes the recruitment and differentiation of endogenous cells in to the implant inside part, which enables a vascularized bone growth into the implant, and forms a structure mimicking the biological ligament–bone interface, thereby significantly improving osteointegration and biomechanical property. Thus, this special design provides an effective SHID‐guided implant‐bioactivation strategy unreached by the traditional manufacturing methods, enlightening a promising technology to develop an ideal SHID for translational use in the future.
Publisher: Oxford University Press (OUP)
Date: 25-04-2021
DOI: 10.1093/RB/RBAB010
Abstract: Titania nanotubes (TNT) generated on titanium implant are emerged as important modification technique to facilitate bone regeneration. Mesenchymal stem cells (MSCs)-derived exosomes are membrane bound extracellular vesicles (EVs), which play an important role in tissue regeneration. The objective of this study was to generate an EVs hybrid TNT aiming at regulating inflammation, MSCs recruitment and osteogenesis. We isolated EVs from MSCs (MSCs EVs) and 3-day osteogenically differentiated MSCs (3d EVs). MSC EVs and 3d EVs exhibited round morphology under TEM, which also showed robust internalization by human bone marrow derived MSCs (hBMSCs). Next, we fabricated 3d EVs/MSC EVs hybrid TNT. When inflammatory macrophages were co-cultured with EVs hybrid TNT, the gene and protein expression of inflammatory cytokine were significantly reduced. Macrophage morphology was also examined by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Further migratory ability study using hBMSCs indicated significant enhancement of MSCs migration in EVs hybrid TNT. In addition, we further demonstrated significant increase of osteogenic differentiation of hBMSCs in EVs hybrid TNT. This study suggests that EVs hybrid TNT may serve as a viable therapeutic approach to enhance osteogenesis and bone regeneration.
Publisher: Elsevier BV
Date: 08-2022
Publisher: Wiley
Date: 29-09-2022
Publisher: MDPI AG
Date: 25-12-2023
DOI: 10.3390/GELS9010011
Abstract: This study reports a novel design of a moisturizing and antimicrobial hydrogel with injectable properties, using a green solvent (glycerol) as a cross-linking agent and gold nanoparticle reduced by Chlorella extract as an antimicrobial approach. We have synthesized gold nanoparticles (AuNPs) with environmentally friendly and bio-safe properties using Chlorella aqueous extracts (AuNPs@Chlorella). Characterization of the nanoparticles by ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), Raman spectrum, and transmission electron microscope (TEM) confirmed that spherical AuNPs with the particle size of 10–20 nm were successfully synthesized. An analysis of the enhancement of the stability of gelatin hydrogels by the addition of glycerol and AuNPs was performed by rheometry. In addition, we also used Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) to confirm the good antibacterial activity. Therefore, the as-prepared gelatin–glycerol hydrogels containing AuNPs@Chlorella are most likely promising alternatives for wound healing dressings.
Publisher: Wiley
Date: 15-10-2023
Publisher: Elsevier BV
Date: 04-2023
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: 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: Elsevier BV
Date: 07-2022
Publisher: Frontiers Media SA
Date: 12-05-2022
DOI: 10.3389/FBIOE.2022.837172
Abstract: Bone regeneration in large segmental defects depends on the action of osteoblasts and the ingrowth of new blood vessels. Therefore, it is important to promote the release of osteogenic/angiogenic growth factors. Since the discovery of heparin, its anticoagulant, anti-inflammatory, and anticancer functions have been extensively studied for over a century. Although the application of heparin is widely used in the orthopedic field, its auxiliary effect on bone regeneration is yet to be unveiled. Specifically, approximately one-third of the transforming growth factor (TGF) superfamily is bound to heparin and heparan sulfate, among which TGF-β1, TGF-β2, and bone morphogenetic protein (BMP) are the most common growth factors used. In addition, heparin can also improve the delivery and retention of BMP-2 in vivo promoting the healing of large bone defects at hyper physiological doses. In blood vessel formation, heparin still plays an integral part of fracture healing by cooperating with the platelet-derived growth factor (PDGF). Importantly, since heparin binds to growth factors and release components in nanomaterials, it can significantly facilitate the controlled release and retention of growth factors [such as fibroblast growth factor (FGF), BMP, and PDGF] in vivo. Consequently, the knowledge of scaffolds or delivery systems composed of heparin and different biomaterials (including organic, inorganic, metal, and natural polymers) is vital for material-guided bone regeneration research. This study systematically reviews the structural properties and auxiliary functions of heparin, with an emphasis on bone regeneration and its application in biomaterials under physiological conditions.
Publisher: Informa UK Limited
Date: 04-2023
DOI: 10.2147/IJN.S397359
Publisher: Springer Science and Business Media LLC
Date: 23-04-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2TB01198K
Abstract: PLGA open porous microspheres (OPMs) with uniform particle size, controllable pore size, good biocompatibility and high cell loading capacity were successfully prepared using a gas-assisted-emulsion and surface-alkalization-treatment technology.
Publisher: Wiley
Date: 17-06-2021
Abstract: Real‐time monitoring of wound healing remains a major challenge in clinical tissue regeneration, calling the need for the development of biomaterial‐guided on‐site monitoring wound healing technology. In this study, multifunctional double colorimetry‐integrated polyacrylamide‐quaternary ammonium chitosan‐carbon quantum dots (CQDs)‐phenol red hydrogels are presented, aiming to simultaneously detect the wound pH level, reduce bacterial infection, and promote wound healing. The hybridization of CQDs and pH indicator (phenol red) with the hydrogels enables their high responsiveness, reversibility, and accurate indication of pH variability to reflect the dynamic wound status in the context of both ultraviolet and visible light. Furthermore, these visual images can be collected by smartphones and converted into on‐site wound pH signals, allowing for a real‐time evaluation of the wound dynamic conditions in a remote approach. Notably, the hydrogels exhibit excellent hemostatic and adhesive properties, maintain sufficient wound moisture, and promote wound healing via their high antibacterial activity (against Staphylococcus Aureus , and Escherichia Coli ) and skin repair function. Overall, the resulting hydrogels have high potential as a novel smart and flexible wound dressing platform for theranostic skin regeneration.
Publisher: Wiley
Date: 28-08-2023
Abstract: Stem cell injection is an effective approach for treating diabetic wounds however, shear stress during injections can negatively affect their stemness and cell growth. Cell‐laden porous microspheres can provide shelter for bone mesenchymal stem cells (BMSC). Herein, curcumin‐loaded flower‐like porous microspheres (CFPM) are designed by combining phase inversion emulsification with thermally induced phase separation‐guided four‐arm poly ( l ‐lactic acid) (B‐PLLA). Notably, the CFPM shows a well‐defined surface topography and inner structure, ensuring a high surface area to enable the incorporation and delivery of a large amount of ‐BMSC and curcumin. The BMSC‐carrying CFPM (BMSC@CFPM) maintains the proliferation, retention, and stemness of ‐BMSCs, which, in combination with their sustainable curcumin release, facilitates the endogenous production of growth roangiogenic factors and offers a local anti‐inflammatory function. An in vivo bioluminescence assay demonstrates that BMSC@CFPM can significantly increase the retention and survival of BMSC in wound sites. Accordingly, BMSC@CFPM, with no significant systemic toxicity, could significantly accelerate diabetic wound healing by promoting angiogenesis, collagen reconstruction, and M2 macrophage polarization. RNA sequencing further unveils the mechanisms by which BMSC@CFPM promotes diabetic wound healing by increasing ‐growth factors and enhancing angiogenesis through the JAK/STAT pathway. Overall, BMSC@CFPM represents a potential therapeutic tool for diabetic wound healing.
Publisher: Springer Science and Business Media LLC
Date: 25-07-2023
Publisher: Elsevier BV
Date: 07-1970
Publisher: Elsevier BV
Date: 10-2022
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: 03-2023
Publisher: American Chemical Society (ACS)
Date: 22-08-2023
Publisher: Elsevier BV
Date: 04-2022
Publisher: Wiley
Date: 03-01-2023
Abstract: Due to the limited self‐repairing capacity after peripheral nerve injuries (PNI), artificial nerve conduits are widely applied to facilitate neural regeneration. Exogenous electrical stimulation (ES) that is carried out by the conductive conduit regulates the biological behavior of Schwann cells (SCs). Meanwhile, a longitudinal surface structure counts to guide axonal growth to accelerate the end‐to‐end connection. Currently, there are no conduits equipped with both electrical conduction and axon‐guiding surface structure. Herein, a biodegradable, conductive poly( l ‐lactide‐ co ‐caprolactone)/graphene (PLCL/GN) composite conduit is designed. The conduit with 20.96 ± 1.26 MPa tensile strength has a micropatterned surface of 20 µm groove fabricated by microimprint technology and self‐assembled polydopamine (PDA). In vitro evaluation shows that the conduits with ES effectively stimulate the directional cell migration, adhesion, and elongation, and enhance neuronal expression of SCs. The rat sciatic nerve crush model demonstrates that the conductive micropatterned conduit with ES promotes the growth of myelin sheath, faster nerve regeneration, and 20‐fold functional recovery in vivo. These discoveries prove that the PLCL(G)/PDA/GN composite conduit is a promising tool for PNI treatment by providing the functional integration of physical guidance, biomimetic biological regulation, and bioelectrical stimulation, which inspires a novel therapeutic approach for nerve regeneration in the future.
Publisher: Elsevier BV
Date: 06-2023
Publisher: Frontiers Media SA
Date: 27-07-2023
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: 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: 08-2021
Publisher: Frontiers Media SA
Date: 25-06-2019
No related grants have been discovered for Lan Xiao.