298 results on '"Hongwei Ouyang"'
Search Results
252. Current research on pharmacologic and regenerative therapies for osteoarthritis
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Wei Zhang, Crispin R. Dass, Hongwei Ouyang, and Jiake Xu
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030203 arthritis & rheumatology ,0301 basic medicine ,Histology ,Physiology ,business.industry ,Endocrinology, Diabetes and Metabolism ,Tanezumab ,Disease ,Osteoarthritis ,Review Article ,Bioinformatics ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,medicine ,Adverse effect ,Autologous chondrocyte implantation ,Induced pluripotent stem cell ,business ,Homing (hematopoietic) ,Sprifermin - Abstract
Osteoarthritis (OA) is a degenerative joint disorder commonly encountered in clinical practice, and is the leading cause of disability in elderly people. Due to the poor self-healing capacity of articular cartilage and lack of specific diagnostic biomarkers, OA is a challenging disease with limited treatment options. Traditional pharmacologic therapies such as acetaminophen, non-steroidal anti-inflammatory drugs, and opioids are effective in relieving pain but are incapable of reversing cartilage damage and are frequently associated with adverse events. Current research focuses on the development of new OA drugs (such as sprifermin/recombinant human fibroblast growth factor-18, tanezumab/monoclonal antibody against β-nerve growth factor), which aims for more effectiveness and less incidence of adverse effects than the traditional ones. Furthermore, regenerative therapies (such as autologous chondrocyte implantation (ACI), new generation of matrix-induced ACI, cell-free scaffolds, induced pluripotent stem cells (iPS cells or iPSCs), and endogenous cell homing) are also emerging as promising alternatives as they have potential to enhance cartilage repair, and ultimately restore healthy tissue. However, despite currently available therapies and research advances, there remain unmet medical needs in the treatment of OA. This review highlights current research progress on pharmacologic and regenerative therapies for OA including key advances and potential limitations.
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- 2016
253. Force and scleraxis synergistically promote the commitment of human ES cells derived MSCs to tenocytes
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Linrong Lu, Huanhuan Liu, Zi Yin, Junfeng Ji, Jialin Chen, Zhi Fang, Qiaomei Tang, Xiao Chen, Hongwei Ouyang, and Weiliang Shen
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musculoskeletal diseases ,Cellular differentiation ,Mice, Nude ,Biology ,Transfection ,Bone morphogenetic protein 2 ,Article ,Cell Line ,Tendons ,Mice ,Osteogenesis ,Basic Helix-Loop-Helix Transcription Factors ,medicine ,Animals ,Humans ,Regeneration ,Cell Lineage ,Progenitor cell ,Embryonic Stem Cells ,Multidisciplinary ,Tissue Engineering ,Regeneration (biology) ,Mesenchymal stem cell ,Scleraxis ,Cell Differentiation ,Mesenchymal Stem Cells ,musculoskeletal system ,Embryonic stem cell ,Tendon ,Cell biology ,medicine.anatomical_structure ,Bone Morphogenetic Proteins ,embryonic structures ,Immunology ,Collagen ,Stress, Mechanical ,Signal Transduction - Abstract
As tendon stem/progenitor cells were reported to be rare in tendon tissues, tendons as vulnerable targets of sports injury possess poor self-repair capability. Human ESCs (hESCs) represent a promising approach to tendon regeneration. But their teno-lineage differentiation strategy has yet to be defined. Here, we report that force combined with the tendon-specific transcription factor scleraxis synergistically promoted commitment of hESCs to tenocyte for functional tissue regeneration. Force and scleraxis can independently induce tendon differentiation. However, force alone concomitantly activated osteogenesis, while scleraxis alone was not sufficient to commit, but augment tendon differentiation. Scleraxis synergistically augmented the efficacy of force on teno-lineage differentiation and inhibited the osteo-lineage differentiation by antagonized BMP signaling cascade. The findings not only demonstrated a novel strategy of directing hESC differentiation to tenocyte for functional tendon regeneration, but also offered insights into understanding the network of force, scleraxis and bmp2 controlling tendon-lineage differentiation.
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- 2012
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254. Electrospun biomimetic scaffold of hydroxyapatite/chitosan supports enhanced osteogenic differentiation of mMSCs
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Yanzhong Zhang, Huanhuan Liu, Bei Feng, Xiao Chen, Hongju Peng, Zi Yin, Huihua Yuan, Bo Su, and Hongwei Ouyang
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Materials science ,Nanofibers ,Bioengineering ,Cell morphology ,Cell Line ,Mice ,stomatognathic system ,Tissue engineering ,Biomimetic Materials ,Osteogenesis ,Animals ,General Materials Science ,Electrical and Electronic Engineering ,Cell Proliferation ,Chitosan ,Tissue Engineering ,Tissue Scaffolds ,Mechanical Engineering ,Regeneration (biology) ,Mesenchymal stem cell ,Biomaterial ,Cell Differentiation ,Mesenchymal Stem Cells ,General Chemistry ,Ascorbic acid ,Alkaline Phosphatase ,nervous system diseases ,Cell biology ,RUNX2 ,Durapatite ,Mechanics of Materials ,Alkaline phosphatase - Abstract
Engaging functional biomaterial scaffolds to regulate stem cell differentiation has drawn a great deal of attention in the tissue engineering and regenerative medicine community. In this study, biomimetic composite nanofibrous scaffolds of hydroxyapatite/chitosan (HAp/CTS) were prepared to investigate their capacity for inducing murine mesenchymal stem cells (mMSCs) to differentiate into the osteogenic lineage, in the absence and presence of an osteogenic supplementation (i.e., ascorbic acid, β-glycerol phosphate, and dexamethasone), respectively. Using electrospun chitosan (CTS) nanofibrous scaffolds as the control, cell morphology, growth, specific osteogenic genes expression, and quantified proteins secretion on the HAp/CTS scaffolds were sequentially examined and assessed. It appeared that the HAp/CTS scaffolds supported better attachment and proliferation of the mMSCs. Most noteworthy was that in the absence of the osteogenic supplementation, expression of osteogenic genes including collagen I (Col I), runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and osteocalcin (OCN) were significantly upregulated in mMSCs cultured on the HAp/CTS nanofibrous scaffolds. Also increased secretion of the osteogenesis protein markers of alkaline phosphatase and collagen confirmed that the HAp/CTS nanofibrous scaffold markedly promoted the osteogenic commitment in the mMSCs. Moreover, the presence of osteogenic supplementation proved an enhanced efficacy of mMSC osteogenesis on the HAp/CTS nanofibrous scaffolds. Collectively, this study demonstrated that the biomimetic nanofibrous HAp/CTS scaffolds could support and enhance the adhesion, proliferation, and particularly osteogenic differentiation of the mMSCs. It also substantiated the potential of using biomimetic nanofibrous scaffolds of HAp/CTS for functional bone repair and regeneration applications.
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- 2012
255. Allogenous Tendon Stem/Progenitor Cells in Silk Scaffold for Functional Shoulder Repair
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Huanhuan Liu, Zi Yin, Weishan Chen, Hongwei Ouyang, Xiao Chen, Jialin Chen, Weiliang Shen, Boon Chin Heng, and School of Materials Science & Engineering
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Scaffold ,Pathology ,medicine.medical_specialty ,Biomedical Engineering ,Silk ,lcsh:Medicine ,Tendons ,Rotator Cuff ,Tissue engineering ,Tendon Injuries ,medicine ,Animals ,Regeneration ,Transplantation, Homologous ,Rotator cuff ,Progenitor cell ,Cell Proliferation ,Transplantation ,Tissue Scaffolds ,Chemistry ,Rotator cuff injury ,Stem Cells ,Graft Survival ,lcsh:R ,Cell Biology ,medicine.disease ,Tendon ,Surgery ,medicine.anatomical_structure ,Gene Expression Regulation ,Cytokines ,Female ,Collagen ,Rabbits ,Stem cell ,Stem Cell Transplantation - Abstract
Tendon stem/progenitor cells (TSPCs) were recently identified within tendon tissues. The aim of this study was to investigate TSPC-seeded knitted silk—collagen sponge scaffold for functional shoulder repair. The multidifferentiation potential, proliferation, and immune properties of TSPCs were investigated in vitro, while the efficacy of TSPC-seeded knitted silk—collagen sponge scaffolds in promoting rotator cuff regeneration was evaluated in vivo within a rabbit model. TSPCs, which exhibited universal stem cell characteristics (i.e., clonogenicity, high proliferative capacity, and multidifferentiation potential), nonimmunogenicity, and immunosuppression, proliferated well on our scaffold in vitro. Implantation of allogenous TSPC-seeded scaffolds within a rabbit rotator cuff injury model did not elicit an immunological reaction, but instead increased fibroblastic cell ingrowth and reduced infiltration of lymphocytes within the implantation sites at 4 and 8 weeks postsurgery. After 12 weeks, the allogenous TSPC-treated group exhibited increased collagen deposition and had better structural and biomechanical properties compared to the control group. This study thus demonstrated that the allogenous TSPC-seeded knitted silk—collagen sponge scaffold enhanced the efficacy of rotator cuff tendon regeneration by differentiating into tenocytes, and by secreting anti-inflammatory cytokines that prevent immunological rejection. Hence, allogenous TSPC-seeded knitted silk—collagen sponge scaffolds can be a clinically useful application for tendon tissue engineering.
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- 2012
256. Platelet-mediated mesenchymal stem cells homing to the lung reduces monocrotaline-induced rat pulmonary hypertension
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Lei Jiang, Pu Liu, Hu Hu, Xing Hui Song, Lin Jing Zhu, Yangzi Jiang, Hongwei Ouyang, Chun Lai Zeng, and Zhangsen Huang
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Blood Platelets ,Male ,Heart Ventricles ,Hypertension, Pulmonary ,Biomedical Engineering ,lcsh:Medicine ,Blood Pressure ,Bone Marrow Cells ,Platelet Glycoprotein GPIIb-IIIa Complex ,Pharmacology ,Mesenchymal Stem Cell Transplantation ,Antibodies ,Rats, Sprague-Dawley ,medicine ,Animals ,Platelet ,Familial Primary Pulmonary Hypertension ,Lung ,Transplantation ,Monocrotaline ,business.industry ,Mesenchymal stem cell ,lcsh:R ,Hemodynamics ,Mesenchymal Stem Cells ,Cell Biology ,medicine.disease ,Pulmonary hypertension ,Rats ,P-Selectin ,medicine.anatomical_structure ,Tirofiban ,Ventricle ,Tyrosine ,Bone marrow ,business ,Homing (hematopoietic) - Abstract
Bone marrow mesenchymal stem cell (BM-MSC) transplantation has been suggested to be a promising method for the treatment of pulmonary arterial hypertension (PAH), a fatal disease currently without effective preventive/therapeutic strategies. However, the detailed mechanisms underlying BM-MSC therapy are largely unknown. We designed the present study to test the hypothesis that circulating platelets facilitate BM-MSC homing to the lung vasculature in a rat model of PAH induced by monocrotalin (MCT). A single subcutaneous administration of MCT induced a marked rise in right ventricular systolic pressure (RVSP) and the weight ratio of right to left ventricle plus septum (RV/LV+S) 3 weeks after injection. The injection of MSCs via tail vein 3 days after MCT significantly reduced the increase of RVSP and RV/LV+S. The fluorescence-labeled MSCs injected into the PAH rat circulation were found mostly distributed in the lungs, particularly on the pulmonary vascular wall, whereas cell homing was abolished by an anti-P-selectin antibody and the GPIIb/IIIa inhibitor tirofiban. Furthermore, using an in vitro flow chamber, we demonstrated that MSC adhesion to the major extracellular matrix collagen was facilitated by platelets and their P-selectin and GPIIb/IIIa. Therefore, the current study suggested that platelet-mediated MSC homing prevented the aggravation of MCT-induced rat PAH, via P-selectin and GPIIb/IIIa-mediated mechanisms.
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- 2012
257. Tendon Injury: Role of Differentiation of Adult and Embryonic Derived Stem Cells
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Hongwei Ouyang, Boon Chin Heng, Chen Xiao, and Yin Zi
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musculoskeletal diseases ,Regeneration (biology) ,Cellular differentiation ,Biology ,musculoskeletal system ,Embryonic stem cell ,Tendon ,Cell biology ,medicine.anatomical_structure ,Tendon cell ,medicine ,Stem cell ,Adult stem cell ,Stem cell transplantation for articular cartilage repair - Abstract
Injuries to tendon are particularly common in sports activities, but there is poor self-repair capability of this unique connective tissue. As understanding of tendon biology is critical for the development of innovative therapy for successful tendon regeneration, the various cell sub-populations in tendon as well as their niche in tendon metabolism and pathology are described. Embryonic and adult stem cell-based tendon tissue engineering approaches have achieved encouraging results. This chapter focuses on introducing two promising strategies: (i) stepwise differentiation of embryonic stem cells for tendon tissue engineering, and (ii) incorporation of the matrix niche into tendon stem cell differentiation for complete tendon regeneration. Multifaceted technologies, such as incorporation of growth factors, bio-scaffolds, mechanical stimulation and genetic modification, are increasingly being utilized to control and direct stem cell differentiation, in the development of novel stem cell-based therapy for effective repair and regeneration of injured tendons.
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- 2011
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258. Cartilage Injuries: Role of Implantation of Human Stem/Progenitor Cells
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Tong Tong, Hongwei Ouyang, Boon Chin Heng, and Yangzi Jiang
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Endothelial stem cell ,medicine.anatomical_structure ,Cartilage ,Regeneration (biology) ,Mesenchymal stem cell ,medicine ,Progenitor cell ,Biology ,Induced pluripotent stem cell ,Embryonic stem cell ,Stem cell transplantation for articular cartilage repair ,Cell biology - Abstract
As articular cartilage has very limited self-repair capability, the repair and regeneration of damaged cartilage is a major challenge. This chapter aims to present the potential seed cell sources that can be utilized for cartilage regeneration, such as autologous chondrocytes (hACs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). One of the promising candidate is cartilage stem/progenitor cell (CSPCs). Current scientific research has demonstrated the existence, definition and niche of CSPCs. The clinical applications of CSPCs show much promise for cartilage regeneration.
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- 2011
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259. Col V siRNA engineered tenocytes for tendon tissue engineering
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Guo Rong Zhang, Xiaohui Zou, Xing Hui Song, Lin-Lin Wang, Ping Lu, and Hongwei Ouyang
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Small interfering RNA ,lcsh:Medicine ,Apoptosis ,Collagen Type I ,Rats, Sprague-Dawley ,Tendons ,Extracellular matrix ,Collagen Type III ,Molecular cell biology ,RNA interference ,Tissue engineering ,Tendon Injuries ,medicine ,Animals ,Protein Isoforms ,RNA, Small Interfering ,lcsh:Science ,Biology ,Extracellular Matrix Adhesions ,Cells, Cultured ,Cell Proliferation ,Multidisciplinary ,Tissue Engineering ,Gene Expression Profiling ,Regeneration (biology) ,lcsh:R ,Fibrillogenesis ,Anatomy ,Transfection ,musculoskeletal system ,Extracellular Matrix ,Rats ,Cell biology ,Tendon ,Collagen Type I, alpha 1 Chain ,medicine.anatomical_structure ,Connective Tissue ,lcsh:Q ,Gene expression ,Collagen Type V ,Research Article - Abstract
The presence of uniformly small collagen fibrils in tendon repair is believed to play a major role in suboptimal tendon healing. Collagen V is significantly elevated in healing tendons and plays an important role in fibrillogenesis. The objective of this study was to investigate the effect of a particular chain of collagen V on the fibrillogenesis of Sprague-Dawley rat tenocytes, as well as the efficacy of Col V siRNA engineered tenocytes for tendon tissue engineering. RNA interference gene therapy and a scaffold free tissue engineered tendon model were employed. The results showed that scaffold free tissue engineered tendon had tissue-specific tendon structure. Down regulation of collagen V α1 or α2 chains by siRNAs (Col5α1 siRNA, Col5α2 siRNA) had different effects on collagen I and decorin gene expressions. Col5α1 siRNA treated tenocytes had smaller collagen fibrils with abnormal morphology; while those Col5α2 siRNA treated tenocytes had the same morphology as normal tenocytes. Furthermore, it was found that tendons formed by coculture of Col5α1 siRNA treated tenocytes with normal tenocytes at a proper ratio had larger collagen fibrils and relative normal contour. Conclusively, it was demonstrated that Col V siRNA engineered tenocytes improved tendon tissue regeneration. And an optimal level of collagen V is vital in regulating collagen fibrillogenesis. This may provide a basis for future development of novel cellular- and molecular biology-based therapeutics for tendon diseases.
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- 2011
260. 112 Stepwise Induction Of Differentiation Of Human Induce Pluripotent Stem Cells Into Teno-lineage
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Yanzhong Zhang, Hongwei Ouyang, Can Zhang, Huanhuan Liu, Huihua Yuan, and Xiao Chen
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Scaffold ,Achilles tendon ,Chemistry ,Regeneration (biology) ,Mesenchymal stem cell ,Physical Therapy, Sports Therapy and Rehabilitation ,General Medicine ,Anatomy ,Regenerative medicine ,Tendon ,Cell biology ,Extracellular matrix ,medicine.anatomical_structure ,medicine ,Orthopedics and Sports Medicine ,Induced pluripotent stem cell - Abstract
Introduction Tendons connect muscles to bone and transmit the force generated during muscle contraction to the skeleton, which are highly prone to injury. Surgical repair is common but natural healing is extremely slow and inefficient. Human-induced pluripotent stem cells (hiPSCs) are highly promising cell source for realising personalised treatments in regenerative medicine [Lian, Q.2010]. Nevertheless, the utility of these cells for tendon tissue engineering has yet not been adequately explored. This study developed a stepwise strategy to induce hiPSCs differentiation into tenocytes and assessed the efficacy of this tissue-engineered construct in promoting tendon regeneration Methods Clonogenicity and multi-differentiation potential were revealed by colony-forming unit (CFU) and different mesodermal lineages differentiation assay respectively. Surface markers were detected by flow cytometry. Well-aligned chitosan-based ultrafine fibers were fabricated with stable jet electrospinning (SJES) technique. Gene expressions were analysed by Q-PCR. A rat Achilles tendon defect model was created and implanted with AC (i.e., aligned fibre scaffold with hiPSC-MSCs) or RC (i.e., random fibre scaffold with hiPSC-MSCs)in vivo. The morphology of repaired tissues were analysed by histological examination and transmission electron microscope. The amount of deposited collagen was quantified using a collagen quantitative assay kit. Mechanical testing was performed for mechanical properties Results and discussion hiPSCs were first induce to mesenchymal stem cells (hiPSC-MSCs) as confirmed by differentiation into three mesenchymal lineages. Flow cytometry and CFU assay showed the expression of characteristic MSC surface markers and clonogenicity. Subsequently, hiPSC-MSCs were differentiated into tenocytes by cultivation on the chitosan-based well-aligned ultrafine fiber scaffold. SEM micrographs and immunofluorescence assays showed that hiPSC-MSCs exhibited tenocyte-like morphology and significantly high expression of tendon-specific genes in the hiPSC-MSCs on well-aligned fibre scaffold. ALP and alizarin red staining showed that the random fibre scaffold induced osteogenesis, while the aligned fibre scaffold hindered the process. In addition, aligned cells expressed significantly higher levels of integrin a1, a2, a5 and b1 subunits, myosin IIB, TGFb3 and SDF-1. In rat Achilles tendon repair model, AC-treated tendon had superior structural and mechanical properties than RC-treated tendon. Cell labelling and extracellular matrix expression assays demonstrated that the transplanted hiPSC-MSCs contributed directly to tendon regeneration. Moreover, no teratoma was found in any samples. These findings present a strategy combining well-aligned fibre scaffold with iPSC-MSCs for tendon regeneration and may assist in clinical regenerative medicine to treat tendon diseases. Reference Lian Q. et al. Circulation. 2010;121:1113–1123
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- 2014
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261. Efficacy of hESC-MSCs in knitted silk-collagen scaffold for tendon tissue engineering and their roles
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Hongwei Ouyang, Boon Chin Heng, Wei Liang Shen, Xiaohui Zou, Jialin Chen, Zi Yin, and Xiao Chen
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Scaffold ,Materials science ,Biophysics ,Silk ,Bioengineering ,Achilles Tendon ,Polymerase Chain Reaction ,Fluorescence ,Biomaterials ,Extracellular matrix ,Prosthesis Implantation ,Mice ,Tissue engineering ,medicine ,Animals ,Humans ,RNA, Messenger ,Cell Shape ,Embryonic Stem Cells ,Wound Healing ,Tissue Engineering ,Tissue Scaffolds ,Mesenchymal stem cell ,Scleraxis ,Mesenchymal Stem Cells ,equipment and supplies ,Embryonic stem cell ,Tendon ,Cell biology ,Biomechanical Phenomena ,Extracellular Matrix ,Rats ,Transplantation ,medicine.anatomical_structure ,Gene Expression Regulation ,Mechanics of Materials ,Organ Specificity ,Ceramics and Composites ,Collagen ,Biomedical engineering ,Stem Cell Transplantation - Abstract
Human embryonic stem cells (hESC) and their differentiated progenies are an attractive cell source for transplantation therapy and tissue engineering. Nevertheless, the utility of these cells for tendon tissue engineering has not yet been adequately explored. This study incorporated hESC-derived mesenchymal stem cells (hESC-MSCs) within a knitted silk-collagen sponge scaffold, and assessed the efficacy of this tissue-engineered construct in promoting tendon regeneration. When subjected to mechanical stimulation in vitro, hESC-MSCs exhibited tenocyte-like morphology and positively expressed tendon-related gene markers (e.g. Collagen type I & III, Epha4 and Scleraxis), as well as other mechano-sensory structures and molecules (cilia, integrins and myosin). In ectopic transplantation, the tissue-engineered tendon under in vivo mechanical stimulus displayed more regularly aligned cells and larger collagen fibers. This in turn resulted in enhanced tendon regeneration in situ, as evidenced by better histological scores and superior mechanical performance characteristics. Furthermore, cell labeling and extracellular matrix expression assays demonstrated that the transplanted hESC-MSCs not only contributed directly to tendon regeneration, but also exerted an environment-modifying effect on the implantation site in situ. Hence, tissue-engineered tendon can be successfully fabricated through seeding of hESC-MSCs within a knitted silk-collagen sponge scaffold followed by mechanical stimulation.
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- 2010
262. Mesenchymal stem cell seeded knitted silk sling for the treatment of stress urinary incontinence
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Yun Long Zhi, Xiaohui Zou, Zi Yin, Hang Mei Jin, Lin-Lin Wang, Hongwei Ouyang, Xiao Chen, and Yangzi Jiang
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medicine.medical_specialty ,Materials science ,Urinary Incontinence, Stress ,Suburethral Sling ,Biophysics ,Silk ,Bioengineering ,Urinary incontinence ,Biocompatible Materials ,Bone Marrow Cells ,Sling (weapon) ,Biomaterials ,Rats, Sprague-Dawley ,Urethra ,Elastic Modulus ,medicine ,Animals ,Humans ,Suburethral Slings ,Tissue engineered ,Tissue Engineering ,Tissue Scaffolds ,Mesenchymal stem cell ,Histology ,Mesenchymal Stem Cells ,Surgery ,Rats ,medicine.anatomical_structure ,Mechanics of Materials ,Ceramics and Composites ,Female ,Sciatic nerve ,Bone marrow ,medicine.symptom - Abstract
Stress urinary incontinence remains a worldwide problem affecting patients of all ages. Implantation of suburethral sling is the cornerstone treatment. Current slings have inherent disadvantages. This study aims to develop a tissue engineered sling with bone marrow derived mesenchymal stem cell seeded degradable silk scaffold. The mesenchymal stem cells were obtained from Sprague-Dawley rats and were characterized in vitro. Layered cell sheets were formed after two weeks of culture and were labeled with carboxyfluorescein diacetate. Forty female rats were divided into four groups: Group A (n=5) had sham operation; other three groups underwent bilateral proximal sciatic nerve transection and were confirmed with stress urinary incontinence by the leak-point pressure measurement at 4 weeks after operation. Then, Group B (n=5) had no sling placed; Group C (n=15) was treated with a silk sling; and Group D (n=15) was treated with the tissue engineered sling. Histology and the leak-point pressure measurements were done at 4 and 12 weeks after the sling implantation while collagen content and mechanical testing were done at 12 weeks. The results showed that Group B had a significantly lower leak-point pressure (24.0+/-4.2 cmH(2)O) at 4 weeks (P0.05), while Group C (38.0+/-3.3 cmH(2)O) and Group D (36.3+/-3.1 cmH(2)O) almost reached to the normal level shown by Group A (41.6+/-3.8 cmH(2)O) (p0.05). At 12 weeks, tissue engineered sling of group D has higher collagen content (70.84+/-14.49 microg/mg) and failure force (2.436+/-0.192 N) when compared those of Group C (38.94+/-7.05 microg/mg and 1.521+/-0.087 N) (p0.05). Both the silk sling and tissue engineered sling showed convincing functional effects for the treatment of stress urinary incontinence in a rat model. And the better ligament-like tissue formation in the tissue engineered sling suggested potential long-term function.
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- 2010
263. In vivo restoration of full-thickness cartilage defects by poly(lactide-co-glycolide) sponges filled with fibrin gel, bone marrow mesenchymal stem cells and DNA complexes
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Wei Wang, Changyou Gao, Yanglin Li, Yangzi Jiang, Bo Li, and Hongwei Ouyang
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Materials science ,Blotting, Western ,Biophysics ,Bioengineering ,Bone Marrow Cells ,Fibrin ,Biomaterials ,Glycosaminoglycan ,chemistry.chemical_compound ,Polylactic Acid-Polyglycolic Acid Copolymer ,In vivo ,medicine ,Animals ,Lactic Acid ,DNA Primers ,biology ,Base Sequence ,Hyaline cartilage ,Reverse Transcriptase Polymerase Chain Reaction ,Cartilage ,Mesenchymal Stem Cells ,Transfection ,DNA ,In vitro ,Cell biology ,PLGA ,medicine.anatomical_structure ,chemistry ,Mechanics of Materials ,Ceramics and Composites ,biology.protein ,Rabbits ,Polyglycolic Acid ,Biomedical engineering - Abstract
A composite construct comprising of bone marrow mesenchymal stem cells (BMSCs), plasmid DNA encoding transforming growth factor-beta1 (pDNA-TGF-beta1), fibrin gel and poly (lactide-co-glycolide) (PLGA) sponge was designed and employed to repair articular cartilage defects. To improve the gene transfection efficiency, a cationized chitosan derivative N,N,N-trimethyl chitosan chloride (TMC) was employed as the vector. The TMC/DNA complexes had a transfection efficiency of 9% to BMSCs and showed heterogeneous TGF-beta1 expression in a 10-day culture period in vitro. In vivo culture of the composite constructs was performed by implantation into full-thickness cartilage defects of New Zealand white rabbit joints, using the constructs absence of pDNA-TGF-beta1 or BMSCs as controls. Heterogeneous expression of TGF-beta1 in vivo was detected at 4 weeks, but its level was decreased in comparison with that of 2 weeks. After implantation for 12 weeks, the cartilage defects were successfully repaired by the composite constructs of the experimental group, and the neo-cartilage integrated well with its surrounding tissue and subchondral bone. Immunohistochemical and glycosaminoglycans (GAGs) staining confirmed the similar amount and distribution of collagen type II and GAGs in the regenerated cartilage as that of hyaline cartilage. The cartilage special genes expressed in the neo-tissue were closer to those of the normal cartilage. An overall score of 2.83 was obtained according to Wakitani's standard. By contrast, only part of the defects was repaired by the pDNA-TGF-beta1 absence constructs, and no cartilage repair but fibrous tissue was found for the BMSCs absence constructs. Therefore, combination of the PLGA sponge/fibrin gel scaffold with BMSCs and gene therapy is an effective method to restore cartilage defects and may have a great potential for practical applications in the near future.
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- 2010
264. Local Delivery of Autologous Platelet in Collagen Matrix Simulated in Situ Articular Cartilage Repair
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Xiao Chen, Hongwei Ouyang, Xing Hui Song, Xiaohui Zou, Lin-Lin Wang, Yangzi Jiang, Hong Xin Cai, and Yi Ying Qi
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Cartilage, Articular ,Male ,Fractures, Cartilage ,Pathology ,medicine.medical_specialty ,Biomedical Engineering ,lcsh:Medicine ,Matrix (biology) ,Transplantation, Autologous ,Glycosaminoglycan ,medicine ,Articular cartilage repair ,Animals ,Autologous chondrocyte implantation ,Glycosaminoglycans ,Transplantation ,Tissue Engineering ,Tissue Scaffolds ,Platelet-Rich Plasma ,Chemistry ,Cartilage ,lcsh:R ,Cell Biology ,medicine.anatomical_structure ,Platelet-rich plasma ,Collagen ,Rabbits ,Bone marrow - Abstract
Bone marrow released by microfracture or full-thickness cartilage defect can initiate the in situ cartilage repair. However, it can only repair small cartilage defects (2). This study aimed to investigate whether autologous platelet-rich plasma (PRP) transplantation in collagen matrix can improve the in situ bone marrow-initiated cartilage repair. Full-thickness cartilage defects (diameter 4 mm, thickness 3 mm) in the patellar grooves of male New Zealand White rabbits were chosen as a model of in situ cartilage repair. They were treated with bilayer collagen scaffold (group II), PRP and bilayer collagen scaffold (group III), and untreated (group I), respectively ( n = 11). The rabbits were sacrificed at 6 and 12 weeks after operation. The repaired tissues were processed for histology and for mechanical test. The results showed that at both 6 and 12 weeks, group III had the largest amounts of cartilage tissue, which restored a larger surface area of the cartilage defects. Moreover, group III had higher histological scores and more glycosaminoglycans (GAGs) content than those in the other two groups ( p < 0.05). The Young's modulus of the repaired tissue in group II and group III was higher than that of group I ( p < 0.05). Autologous PRP and bilayer collagen matrix stimulated the formation of cartilage tissues. The findings implicated that the combination of PRP with collagen matrix may repair larger cartilage defects that currently require complex autologous chondrocyte implantation (ACI) or osteochondral grafting.
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- 2009
265. Tendon tissue engineering with mesenchymal stem cells and biografts: an option for large tendon defects?
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Xiaohui Zou, Hongwei Ouyang, Guo Li Yin, and Xiao Chen
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General Immunology and Microbiology ,Biocompatibility ,Tissue Engineering ,Regeneration (biology) ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Tendon tissue ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Tendon ,Tendons ,medicine.anatomical_structure ,Physical structure ,Tissue engineering ,In vivo ,medicine ,Humans ,Biomedical engineering - Abstract
The most important factors in the tissue engineering approach to tissue repair and regeneration are the use of appropriate cells and scaffolds. Mesenchymal stem cells (MSCs) are one of the most promising seed cells, which can be easily derived and have the potential to differentiate into various mesenchymal cell types as well as tenocytes in vitro and in vivo. Biological tendon grafts are the most common choice in current clinical practice, as they possess physical structure, strength and biocompatibility. We review the latest research findings on MSC-based tendon tissue engineering and recent advances in biological graft research.
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- 2009
266. Human Embryonic Stem Cell-derived Mesenchymal Stem Cells and BMP7 Promote Cartilage Repair
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Lin-Lin Wang, Hongwei Ouyang, Xiaohui Zou, Yangzi Jiang, Xiao Chen, Xing Hui Song, and Yi Ying Qi
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Pathology ,medicine.medical_specialty ,Chemistry ,Hyaline cartilage ,Cartilage ,Mesenchymal stem cell ,Clinical uses of mesenchymal stem cells ,Amniotic stem cells ,medicine.anatomical_structure ,embryonic structures ,medicine ,Stem cell ,Stem cell transplantation for articular cartilage repair ,Adult stem cell - Abstract
ESCs are pluripotential, but their application for cartilage regenration has not been explored. Our study was designed to explore a strategy of using human embryonic stem cell-derived mesenchymal stem cells(hESC-MSCs) with BMP7 in collagen scaffold to improve the therapeutic efficacy of cartilage defect repair. Full-thickness cartilage defects (diameter= 2mm, thickness=2 mm) were made in the patellar grooves of male SD rat and randomly divided into four groups: No treatment group, collagen scaffold group, hESC-MSCs in collagen scaffold group or hESC-MSCs with BMP7 in collagen scaffold group, respectively (n=11 in each group). The rats were sacrificed at 4 and 8 weeks after operation. The repaired tissues were processed for histology and for mechanical test. The histological results showed that the group treated with hESC-MSCs had more amounts of hyaline cartilage, higher ICRS histological scores and Young’s modulus of the repaired cartilage tissue. Moreover, hESC-MSCs with BMP7 group had the highest histological scores and Young’s modulus of the repaired cartilage tissue. The amounts of hyaline cartilage were significantly higher than those in hESC-MSCs group. Our results demonstrated that hESC-MSCs can improve the regeneration of cartilage tissue. It acts synergistically with BMP7 in stimulating the formation of hyaline cartilage tissues. These findings suggested that the combination of hESC-MSCs with BMP7 in collagen matrix may be used to improve the quality of cartilage repair.
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- 2009
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267. Local Delivery of Autologous Platelet in Collagen Matrix Synergistically Stimulated In-situ Articular Cartilage Repair
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Yi Ying Qi, Xiao Chen, Nguyen Thi Minh Hieu, Yangzi Jiang, Hongwei Ouyang, Lin-Lin Wang, and Hong Xin Cai
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In situ ,Pathology ,medicine.medical_specialty ,Materials science ,Cartilage ,food and beverages ,Matrix (biology) ,Transplantation ,medicine.anatomical_structure ,medicine ,Articular cartilage repair ,Autologous platelet ,Bone marrow ,Cartilage repair ,Biomedical engineering - Abstract
Objective: Microfracture is a routine therapy to release bone marrow from subchondral bone for in-situ cartilage repair. However, it can only treat small cartilage defects (< 2 cm2). The study aims to investigate whether autologous platelet rich plasma (PRP) transplantation in collagen matrix can synergistically improve the in-situ bone marrow-initiated cartilage repair.
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- 2009
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268. Novel Composite Membrane Guides Cortical Bone Regeneration
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You Zhi Cai, Xiaohui Zou, Yi Ying Qi, Hong Xin Cai, Lin-Lin Wang, and Hongwei Ouyang
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medicine.anatomical_structure ,Membrane ,Materials science ,Tissue engineering ,Regeneration (biology) ,Bone cell ,medicine ,Cortical bone ,Matrix (biology) ,Bone regeneration ,Bone tissue ,Biomedical engineering - Abstract
Current treatment options for restoring large bony defects due to trauma or tumor ablation are limited by the host bone tissue availability and donor site morbidity of bone implantation. Creation of implantable functional bone tissue that could restore bony defects may be a possible solution. Previously, many in vitro studies have indicated the potential of using electrospun nanofibrous scaffolds for tissue repair. However, few studies demonstrated their utility in tissue repair models. We hypothesized that the electrospun nanofibrous membrane improves the efficacy of currently-used collagenous guided bone regeneration (GBR) membrane in repairing large cortical bony defect. A practical biodegradable nanofibrous poly-L-lactic-acid (PLLA) membrane honeycombed with one layer of collagen matrix was developed. Bone defect with 10 x 15 mm2 area was covered by nanofiber-reinforced bi-layer membrane or collagenous membrane. 3 and 6 weeks after operation, bone defect healing was assessed radiologically and histologically. The radiolographic data showed that the group treated with nanofiber-reinforced bi-layer membrane had more bony tissue formation at 3 weeks. The histology results were consistent with that of radiographic findings at 3 weeks. Moreover, the defects treated with bi-layer membrane were repaired perfectly by dense cortical bone at 6 weeks, while whose treated with collagenous membrane were filled with spongy bone and fibrous tissues. The results demonstrated that electrospun nanofibrous membrane can be combined with collagenous GBR membrane to improve guided bone regeneration technology. And this type of membrane may provide implantable functional bone tissues for patients with large bone defects.
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- 2009
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269. Synergic Combination of Collagen Matrix with Knitted Silk Scaffold Regenerated Ligament with More Native Microstructure in Rabbit Model
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Yi-Ying Qi, Xiao Chen, Zi Yin, Lin-Lin Wang, and Hongwei Ouyang
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Scaffold ,Materials science ,Tendon tissue ,Matrix (biology) ,musculoskeletal system ,Microstructure ,SILK ,medicine.anatomical_structure ,Tissue engineering ,Rabbit model ,Ligament ,medicine ,Composite material ,Biomedical engineering - Abstract
A number of researches on ligament and tendon tissue engineering scaffold have been carried out. However, a scaffold which simultaneously possesses optimal strength, porous structure and biocompatible microenvironment is yet to be developed. This study aims to design a new practical ligament scaffold by synergic incorporation of silk material, knitting structure and collagen matrix.
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- 2009
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270. Cell Orientation Affects Human Tendon Stem Cells Differentiation
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T. M. Hieu Nguyen, Xiao Chen, Hongwei Ouyang, and Zi Yin
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musculoskeletal diseases ,medicine.anatomical_structure ,Nanofiber ,Cell ,Cell model ,medicine ,Connective tissue ,Matrix (biology) ,Stem cell ,musculoskeletal system ,Tendon ,Cell biology - Abstract
Tendon is a specific connective tissue composed of parallel collagen fibers. The effect of matrix orientation on tendon differentiation has not been investigated. The recent discovery of tendon stem cells (TSPCs) [1] provided an ideal cell model for tendon biology study. This study focused on investigating the effect of cell orientation, which induced by aligned electrospun poly (L-lactic acid) (PLLA) nanofibers, on human TSPCs differentiation..
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- 2009
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271. Comparison the Effects of BMP-4 and BMP-7 on Articular Cartilage Repair with Bone Marrow Mesenchymal Stem Cells
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Yangzi Jiang, Yi Ying Qi, Xiaohui Zou, Lin-Lin Wang, and Hongwei Ouyang
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Bone morphogenetic protein 7 ,animal structures ,Tissue engineering ,Regeneration (biology) ,embryonic structures ,Mesenchymal stem cell ,Articular cartilage repair ,Biology ,Chondrogenesis ,Bone morphogenetic protein ,Cell biology ,Stem cell transplantation for articular cartilage repair - Abstract
To compare the potential effects of bone morphogenetic proteins 4 and 7 (BMP-4 and BMP-7) on the chondrogenic differentiation of mesenchymal stem cells(MSCs) for articular cartilage regeneration in vitro and in vivo.
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- 2009
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272. Ligament regeneration using a knitted silk scaffold combined with collagen matrix
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Zi Yin, Hongwei Ouyang, Yi-Ying Qi, Lin-Lin Wang, Xiao Chen, Guo-Li Yin, and Xiaohui Zou
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Scaffold ,Materials science ,Biophysics ,Silk ,Bioengineering ,macromolecular substances ,Matrix (biology) ,Biomaterials ,Tissue engineering ,Microscopy, Electron, Transmission ,medicine ,Animals ,Regeneration ,Cells, Cultured ,DNA Primers ,Ligaments ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Regeneration (biology) ,fungi ,In vitro ,medicine.anatomical_structure ,SILK ,Mechanics of Materials ,Ceramics and Composites ,Ligament ,Microscopy, Electron, Scanning ,Female ,Collagen ,Rabbits ,Collagen scaffold ,Biomedical engineering - Abstract
This study was aimed to develop a new practical ligament scaffold by synergistic incorporation of silk fibers, a knitted structure, and a collagen matrix. The efficacy for ligament tissue engineering was investigated in vitro and in animal models. Cells cultured on a collagen substrate expressed ligament matrix genes at higher levels than those on a silk substrate. The silk scaffold elicited little inflammatory reaction and degraded slowly after subcutaneous implantation in a mouse model. In the rabbit MCL defect model, MCLs treated with a silk+collagen scaffold deposited more collagen, had better mechanical properties, and showed more native microstructure with larger diameter collagen fibrils and stronger scaffold-ligament interface healing than untreated MCLs and those treated with silk scaffolds. These results demonstrated that the knitted silk+collagen sponge scaffold improves structural and functional ligament repair by regulating ligament matrix gene expression and collagen fibril assembly. The findings are the first to highlight the important roles of biomaterials in ligament regeneration biology. Also, the concept of an "internal-space-preservation" scaffold is proposed for the tissue repair under physical loading.
- Published
- 2008
273. Effects of Bovine Kidney Heparan Sulphate and Shark Cartilage Chondroitin-6-Sulphate on Palatal Fibroblast Activities
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Weng-Chiong Foong, Xiaohui Zou, Tong Cao, Boon-Huat Bay, George W. Yip, and Hongwei Ouyang
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Bovine kidney ,chemistry.chemical_compound ,medicine.anatomical_structure ,Heparan sulphate ,Chemistry ,medicine ,Chondroitin ,Anatomy ,Shark cartilage ,Fibroblast ,Molecular biology - Published
- 2007
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274. P169 In vitro study of effect of chondroitin sulfate on human chondroctyes
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James Hoi Po Hui, Hongwei Ouyang, E.H. Lee, J.S.W. Chong, and S. Chan
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chemistry.chemical_compound ,Biochemistry ,Rheumatology ,Chemistry ,Biomedical Engineering ,In vitro study ,Orthopedics and Sports Medicine ,Chondroitin sulfate - Published
- 2007
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275. Musculoskeletal regeneration research network : A global initiative
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Herb B. Sun, Lars Lidgren, Kai-Ming Chan, Rocky S. Tuan, Jos Malda, Geoff Richards, Li Felländer-Tsai, Daniel B.F. Saris, William J. Maloney, Ming Ding, Christer Rolf, Hongwei Ouyang, Chelsea Hopkins, Ling Qin, Lei Wei, Stuart B. Goodman, Tingting Tang, Sai-Chuen Fu, Gang Li, Xiaoling Zhang, René M. Castelein, and Developmental BioEngineering
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medicine.medical_specialty ,lcsh:Diseases of the musculoskeletal system ,Editorial ,business.industry ,Orthopedic surgery ,Alternative medicine ,medicine ,MEDLINE ,Physical therapy ,Musculoskeletal regeneration ,Orthopedics and Sports Medicine ,lcsh:RC925-935 ,business - Published
- 2015
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276. Can the therapeutic advantages of allogenic umbilical cord blood-derived stem cells and autologous bone marrow-derived mesenchymal stem cells be combined and synergized?
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Boon Chin Heng, Toan Thang Phan, Hongwei Ouyang, Hua Liu, and Tong Cao
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business.industry ,Mesenchymal stem cell ,Biomedical Engineering ,Biophysics ,Clinical uses of mesenchymal stem cells ,Bioengineering ,Amniotic stem cells ,General Medicine ,Mesenchymal Stem Cell Transplantation ,Transplantation, Autologous ,Cord lining ,Biomaterials ,Endothelial stem cell ,Cancer research ,Medicine ,Animals ,Humans ,Regeneration ,Transplantation, Homologous ,Cord Blood Stem Cell Transplantation ,Stem cell ,business ,Cellular Senescence ,Adult stem cell ,Stem cell transplantation for articular cartilage repair - Published
- 2006
277. Efficacy of bone marrow-derived stem cells in strengthening osteoporotic bone in a rabbit model
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Zhuo Wang, Jeniffer Sue Wee Chong, Shamal Das De, Hongwei Ouyang, James C.H. Goh, Eng Hin Lee, Siew Leng Low, and Zigang Ge
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Ovariectomy ,Osteoporosis ,Bone Marrow Cells ,Mesenchymal Stem Cell Transplantation ,Andrology ,Osteogenesis ,medicine ,Animals ,Femur ,Cells, Cultured ,biology ,business.industry ,Mesenchymal stem cell ,General Engineering ,Osteoblast ,Mesenchymal Stem Cells ,medicine.disease ,Transplantation ,Disease Models, Animal ,medicine.anatomical_structure ,Immunology ,Osteocalcin ,biology.protein ,Alkaline phosphatase ,Female ,Bone marrow ,Rabbits ,business ,Immunostaining - Abstract
Osteoporosis might be due to defects in mesenchymal stem cells (MSCs) that lead to reduced proliferation and osteoblast differentiation. We hypothesized that transplantation of MSCs into sites at risk for developing osteoporotic bone could improve bone structure and biomechanics. The aim of this study was to establish an osteoporosis rabbit model by ovariectomy (OVX), characterize the autologous MSCs from the OVX rabbits, and transplant the autologous MSCs into the OVX rabbits. MSCs harvested from bone marrow of normal and OVX rabbits were culture expanded and differentiated in osteogenic medium. Phenotypes were evaluated by collagen I immunostaining, von Kossa staining, and quantitative assays of bone-specific alkaline phosphatase (B-ALP) and osteocalcin (OCN). MSCs were transfected with green fluorescence protein (GFP) and implanted in the gluteus muscle to trace their fate in vivo. Cultured autologous MSCs from OVX rabbits were constructed in calcium alginate gels and then transplanted in the distal femurs. At 4 and 8 weeks after implantation, histomorphometrical and biomechanical analyses were performed on the samples. MSCs from OVX rabbits displayed higher B-ALP activity, but had similar OCN levels as compared to those from sham rabbits. After 8 weeks of implantation, more bone apposition was found in the MSC-alginate-treated group. Histomorphometry indicated increased trabecular thickness. Histology also illustrated improved microstructures with newly formed osteoids and enhanced trabecular thickness. In addition, biomechanical testing revealed stronger stiffness in the MSC-alginate treatment group. Therefore, this study implies that transplantation of MSCs can help to strengthen osteoporotic bone in rabbits.
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- 2006
278. Mesenchymal stem cell sheets revitalize nonviable dense grafts: implications for repair of large-bone and tendon defects
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Boon Chin Heng, Xing Hui Song, Tong Cao, Xiaohui Zou, Hongwei Ouyang, He Feng Huang, and Ling Ling Wang
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Adult ,Adolescent ,Mesoderm ,Tendons ,medicine ,Living Donors ,Animals ,Humans ,Transplantation, Homologous ,Transplantation ,Periosteum ,Bone Transplantation ,Chemistry ,Demineralized bone matrix ,Stem Cells ,Mesenchymal stem cell ,Anatomy ,Middle Aged ,Ascorbic acid ,Tissue Graft ,Tendon ,Disease Models, Animal ,medicine.anatomical_structure ,Tendinopathy ,Female ,Rabbits ,Stem cell ,Bone Diseases ,Biomedical engineering ,Stem Cell Transplantation - Abstract
Background Large musculoskeletal defects are commonly reconstructed with allogeneic grafts. As cryopreserved allogeneic grafts lack viable cells, this often results in poorer clinical outcome. Current technology can not incorporate large number of cells to the dense grafts. This study aimed to investigate the feasibility of fabricating sheets of mesenchymal stem cells (MSCs) to revitalize cryopreserved grafts. Methods Human MSCs were isolated, characterized, and cultured to form a cell sheet in the presence of ascorbic acid. Once a sheet of MSCs was obtained, it was assembled onto the demineralized bone grafts or frozen tendon grafts by a wrapping technique. Then the assembled structure was cultured for 3 weeks. The macro morphology, histology, and immunohistochemistry of the grafts were evaluated. Results It was found that MSCs were able to form coherent cellular sheets within 3 weeks. When assembled with demineralized bone matrix, MSC sheets were similar to in situ periosteum and were able to differentiate into the osteochondral lineage. When assembled with frozen tendon graft, MSCs sheets were well-incorporated within the tissue sheath (peritenon) around the tendon, and adopted the characteristic spindle-shaped morphology of tenocyte-like cells. Conclusions The results therefore demonstrated that MSCs sheets are easily fabricated and can maintain their differentiation potential within particular scaffolds, which would suggest a novel and convenient strategy for revitalizing large tissue grafts to improve clinical outcome.
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- 2006
279. Osteoarthritis and therapy
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Boon Chin Heng, Hongwei Ouyang, Tong Cao, Zheng Yang, Zigang Ge, Yang Hu, and Eng Hin Lee
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Chondropathy ,Cartilage, Articular ,medicine.medical_specialty ,Bone density ,Immunology ,Population ,Osteoarthritis ,Chondrocytes ,Rheumatology ,Internal medicine ,Synovitis ,medicine ,Immunology and Allergy ,Humans ,Pharmacology (medical) ,education ,education.field_of_study ,business.industry ,Cartilage ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Joint pain ,Eburnation ,Cytokines ,medicine.symptom ,business - Abstract
Introduction Osteoarthritis (OA) is the leading cause of disability in older persons, affecting 10% of the population 60 years of age. In the United States alone, there are currently at least 20 million persons afflicted with OA, which costs the economy approximately $60 billion annually. Eighty percent of individuals with OA have limited mobility and 25% cannot perform major daily activities (1). Because the population is aging rapidly, it is anticipated that OA will affect almost 60 million individuals in the United States by 2020, with consequent increased spending on diagnosis, therapy, side-effect prevention, and loss of productivity. Most cases of OA develop without a known cause of joint degeneration in what is referred to as primary or idiopathic OA. Less frequently, OA develops as a result of joint degeneration caused by traumatic injury or a variety of hereditary; inflammatory; or developmental, metabolic, and neurologic disorders, a group of conditions referred to as secondary OA. Genetic predisposition, age, obesity, female sex, greater bone density, joint laxity, and excessive mechanical loading have been identified as risk factors for primary OA (1). OA diseases are a result of both mechanical and biologic events that destabilize the normal coupling of degradation and synthesis of articular cartilage chondrocytes, extracellular matrix, and subchondral bone. Ultimately, OA diseases are manifested by morphologic, biochemical, molecular, and biomechanical changes to both cells and extracellular matrix, which lead to softening, fibrillation, ulceration, loss of articular cartilage, sclerosis, and eburnation of subchondral bone, osteophytes, and subchondral cysts. When clinically evident, OA diseases are characterized by joint pain, tenderness, limitation of movement, crepitus, occasional effusion, and variable degrees of inflammation without systemic effects (2). Although intensive research has been carried out on the effects of different cytokines, growth factors, and mechanical loading on the regeneration of cartilage and subchondral bone, there is still no comprehensive understanding of mechanism of OA. Although synovitis is not directly related to the severity of OA (3), it is proposed to be involved with the progression of OA and can be predictive of future chondropathy (4). Therefore, it is imperative to develop a better understanding of how synovitis affects the progression of OA. Recently, the potential role of subchondral bone in the mechanism of OA has attracted more attention. Several theories relate subchondral bone to OA. First, a stiffer subchondral bone, either caused by healing of trabecular microfacture (5) or abnormal metabolism of osteoblasts (6), is no longer an effective shock absorber and causes damage to cartilage. Second, abnormal function of OA osteoblasts in subchondral bone may lead to an increase in bone volume without a concomitant increase in mineralization due to an inappropriate isoform and structure of collagen, which reduces bone strength (6). Third, bone-derived products (7) and cytokines from subchondral bone (8) may pass through channels and fissures between cartilage and bone to initiate OA (9). Much clinical therapy of OA is focused on improving conditions of OA in subchondral bone.
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- 2006
280. Characterization of a novel polymeric scaffold for potential application in tendon/ligament tissue engineering
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Tong Earn Tay, James C.H. Goh, Siew L. Toh, Hongwei Ouyang, and Sambit Sahoo
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Scaffold ,Stromal cell ,Decorin ,Polymers ,Swine ,Biocompatible Materials ,Bone Marrow Cells ,Extracellular matrix ,Tendons ,chemistry.chemical_compound ,Tissue engineering ,Polylactic Acid-Polyglycolic Acid Copolymer ,Materials Testing ,medicine ,Animals ,Lactic Acid ,Cells, Cultured ,Extracellular Matrix Proteins ,Ligaments ,Microscopy, Confocal ,Tissue Engineering ,Chemistry ,Reverse Transcriptase Polymerase Chain Reaction ,Biglycan ,General Engineering ,Tendon ,Nanostructures ,PLGA ,medicine.anatomical_structure ,Stromal Cells ,Polyglycolic Acid ,Biomedical engineering - Abstract
Unlike braided fabrics, knitted scaffolds have been proven to favor deposition of collagenous connective tissue matrix, which is crucial for tendon/ligament reconstruction. But cell seeding of such scaffolds often requires a gel system, which is unstable in a dynamic situation, especially in the knee joint. This study developed a novel, biodegradable nano-microfibrous polymer scaffold by electrospinning PLGA nanofibers onto a knitted PLGA scaffold in order to provide a large biomimetic surface for cell attachment. Porcine bone marrow stromal cells were seeded onto either the novel scaffolds by pipetting a cell suspension (Group I) or the knitted PLGA scaffolds by immobilizing in fibrin gel (Group II). Cell attachment at 36 hours, cell proliferation and extracellular matrix synthesis at 1 week, and mechanical properties over 2 weeks were investigated. Cell attachment was comparable and cell proliferation was faster in Group I. Moreover, cellular function was more actively exhibited in Group I, as evident by the higher expression of collagen I, decorin, and biglycan genes. Thus, this novel scaffold, facilitating cell seeding and promoting cell proliferation, function, and differentiation, could be applied with promise in tissue engineering of tendon/ligament.
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- 2006
281. Kdm6b regulates cartilage development and homeostasis through anabolic metabolism.
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Jun Dai, Dongsheng Yu, Yafei Wang, Yishan Chen, Heng Sun, Xiaolei Zhang, Shouan Zhu, Zongyou Pan, Boon Chin Heng, Shufang Zhang, Hongwei Ouyang, Dai, Jun, Yu, Dongsheng, Wang, Yafei, Chen, Yishan, Sun, Heng, Zhang, Xiaolei, Zhu, Shouan, Pan, Zongyou, and Heng, Boon Chin
- Abstract
Objectives: Epigenetic mechanisms have been reported to play key roles in chondrogenesis and osteoarthritis (OA) development. Here, we sought to identify specific histone demethylases that are involved and delineate the underlying mechanisms.Methods: We screened the expression of 17 distinct histone demethylases by quantitative real time PCR (qRT-PCR) during chondrogenic differentiation of C3H10T1/2 cells. The role of Kdm6b in cartilage development was then analysed with transgenic Col2a1-CreERT2;Kdm6bf/f . RNA-Seq was applied to explore the underlying changes in chondrocytes upon knockdown of Kdm6b. Experimental OA in mice was induced by destabilisation of the medial meniscus in C57BL/6J (wild type, Kdm6bf/f and Col2a1-CreERT2;Kdm6bf/f ) mice, either with intra-articular injection of shKdm6b lentivirus or after tamoxifen treatment. Mouse joints and human cartilage samples were used for histological analysis.Results: Kdm6b expression was significantly increased during cartilage development. Col2a1-CreERT2;Kdm6bf/f mice displayed obvious skeletal abnormalities at E16.5 and E18.5 with intraperitoneal injection of tamoxifen at E12.5. RNA-Seq and qRT-PCR analyses revealed decreased expression of chondrocyte anabolic genes in Col2a1-CreERT2;Kdm6bf/f chondrocytes. The histological OA score was significantly higher in mice injected with Kdm6b short hairpin RNA lentivirus. Col2a1-CreERT2;Kdm6bf/f mice exhibited accelerated OA development at 8 and 12 weeks following surgical induction. The number of Kdm6b-positive chondrocytes was lower in both mice and human OA cartilage samples.Conclusions: These findings indicate that knockdown of Kdm6b in chondrocytes leads to abnormal cartilage development and accelerated OA progression via inhibition of the anabolic metabolism of chondrocytes. Understanding the epigenetic mechanism of joint cartilage development and homeostasis would be useful for development of new therapeutic modalities for OA. [ABSTRACT FROM AUTHOR]- Published
- 2017
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282. Loss of viability during freeze-thaw of intact and adherent human embryonic stem cells with conventional slow-cooling protocols is predominantly due to apoptosis rather than cellular necrosis
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Zheng Yang, Eng Hin Lee, Abdul Jalil Rufaihah, Boon-Huat Bay, Hongwei Ouyang, Hua Liu, Wei Seong Toh, Tong Cao, Boon Chin Heng, Chao Peng Ye, and Zigang Ge
- Subjects
Programmed cell death ,Cell Survival ,Endocrinology, Diabetes and Metabolism ,Cellular differentiation ,Clinical Biochemistry ,Apoptosis ,DNA Fragmentation ,Biology ,Necrosis ,Cryoprotective Agents ,Microscopy, Electron, Transmission ,Freezing ,In Situ Nick-End Labeling ,Humans ,Pharmacology (medical) ,Fragmentation (cell biology) ,Molecular Biology ,Cryopreservation ,TUNEL assay ,Stem Cells ,Biochemistry (medical) ,Temperature ,Cell Differentiation ,Cell Biology ,General Medicine ,Embryo, Mammalian ,Molecular biology ,Chromatin ,Cell biology ,Kinetics ,Terminal deoxynucleotidyl transferase ,DNA fragmentation ,Stem cell - Abstract
A major challenge in the widespread application of human embryonic stem (hES) cells in clinical therapy and basic scientific research is the development of efficient cryopreservation protocols. Conventional slow-cooling protocols utilizing standard cryoprotectant concentrations i.e. 10% (v/v) DMSO, yield extremely low survival rates of5% as reported by previous studies. This study characterized cell death within frozen-thawed hES colonies that were cryopreserved under standard conditions. Surprisingly, our results showed that immediately after post-thaw washing, the overwhelming majority of hES cells were viable (approximately 98%), as assessed by the trypan blue exclusion test. However, when the freshly-thawed hES colonies were incubated within a 37 degrees C incubator, there was observed to be a gradual reduction in cell viability over time. The kinetics of cell death was drastically slowed-down by keeping the freshly-thawed hES colonies at 4 degrees C, with90% of cells remaining viable after 90 min of incubation at 4 degrees C. This effect was reversible upon re-exposing the cells to physiological temperature. The vast majority of low temperature-exposed hES colonies gradually underwent cell death upon incubation for a further 90 min at 37 degrees C. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) assay confirmed apoptosis-induced nuclear DNA fragmentation in frozen-thawed hES cells after incubation at 37 degrees C for 90 min. Expression of active caspase-3 enzyme, which is another prominent marker of apoptosis, was confirmed by immunocytochemical staining, while transmission electron microscopy showed typical ultrastructural features of apoptosis such as chromatin condensation and margination to the nuclear membrane. Hence, our results demonstrated that apoptosis instead of cellular necrosis, is the major mechanism of the loss of viability of cryopreserved hES cells during freeze-thawing with conventional slow-cooling protocols.
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- 2005
283. Assembly of bone marrow stromal cell sheets with knitted poly (L-lactide) scaffold for engineering ligament analogs
- Author
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Tong Earn Tay, Hongwei Ouyang, James C.H. Goh, Siew Lok Toh, and Kyaw Moe
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Scaffold ,Stromal cell ,Materials science ,Ligaments ,Tissue Engineering ,Swine ,Anterior cruciate ligament ,Polyesters ,Biomedical Engineering ,Biocompatible Materials ,Bone Marrow Cells ,Adhesion ,Ascorbic acid ,Biomaterials ,Collagen Type III ,medicine.anatomical_structure ,Tissue engineering ,Ligament ,medicine ,Animals ,Stromal Cells ,Cells, Cultured ,Biomedical engineering - Abstract
The current cell seeding technique has several disadvantages, such as low efficiency of cell attachment to scaffolds and the limited strength of cell-gel composite adhesion to scaffold. These problems warrant further study to improve the assembly of cell to scaffold. Therefore this study aims to fabricate a bone marrow stromal cells (bMSCs) sheet and assemble it on a knitted poly (L-lactide) (PLLA) scaffold for engineering ligament analogs. bMSCs were cultured to form a cell sheet in the presence of ascorbic acid. Once a sheet of bMSCs was obtained, it was assembled onto the knitted scaffold by a wrapping technique. Then the assembled structure was held in place in a spinner flask for 4 weeks. The macromorphology, histology, and biomechanics of the grafts were evaluated. The composite of cell sheet/PLLA scaffold constructs had transformed into tissuelike ligament analogs. Immunohistochemical analysis showed that the components of the analogs were similar to that of ligament tissues, consisting primarily of collagen type I and small amount of collagen type III and tenascin. The failure force of the cell/scaffold assembly under tension (46.68+/-2.29 N) was higher than that of the scaffold group (43.58+/-2.41 N; p
- Published
- 2005
284. Ligament and Tendon Repair with Adult Stem Cells
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James C.H. Goh, Sambit Sahoo, and Hongwei Ouyang
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medicine.anatomical_structure ,medicine ,Ligament ,Anatomy ,Biology ,Adult stem cell ,Tendon - Published
- 2005
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285. Anchoring dental implant in tissue-engineered bone using composite scaffold: a preliminary study in nude mouse model
- Author
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Hongwei Ouyang, Fulin Chen, Xue Feng, Tieshan Liu, Tianqiu Mao, Guifang Zhao, Yaowu Yang, Zhan Gao, and Xiaohui Zou
- Subjects
Scaffold ,Stromal cell ,Bone density ,medicine.medical_treatment ,Dentistry ,Mice, Nude ,Dental Prosthesis Retention ,Mice ,Nude mouse ,Tissue engineering ,medicine ,Animals ,Dental implant ,Bone Marrow Transplantation ,Dental Implants ,biology ,Tissue Engineering ,business.industry ,Dental Implantation, Endosseous ,biology.organism_classification ,Otorhinolaryngology ,Bone Substitutes ,Models, Animal ,Surgery ,Cattle ,Implant ,Rabbits ,Oral Surgery ,Stromal Cells ,business - Abstract
Purpose The purpose of this study was to fabricate a tissue-engineered bone graft anchoring dental implant with bone marrow stromal cell (bMSC) seeded coral-implant composite scaffold. Materials and methods Titanium dental implants (3 mm in diameter) were inserted into the cylinder coral scaffolds (5 mm in diameter and 1 mm in wall thickness). bMSCs were isolated from iliac bone marrow of adult New Zealand White rabbits, induced by dexamethasone and seeded into the composite scaffold at the density of 2 × 10 8 /mL in 200 μL medium. Nine cell coral-implant complexes were incubated in vitro for 5 days. One complex was processed for scanning electronic microscopy. The other 8 complexes, together with 4 coral scaffold without cell acting as control, were implanted subcutaneously into nude mice back. At 1 and 2 months after implantation, 4 specimens from the experiment group and 2 specimens from the control group were harvested respectively. New bone restoration and new bone integration with dental implant were evaluated by gross inspection, manual handling test, radiographic examination, and histologic observation. Results Specimens harvested at 2 months after implantation were red and similar to native bone. Manual handling test showed that dental implants were fixed in the newly formed bone. Radiographic examination showed that most of the coral scaffold had been absorbed. Bone density x-ray shadow could be observed around the dental implant. Histologic examination showed that large amount of new bone formed around the dental implants and integrated well with the implants in some area. In the control group no bone formation was observed both macroscopically and microscopically. Conclusion The results of the study suggested that the tissue-engineered bone of bMSCs seeded natural coral-implant composite scaffold is promising for dental implant anchoring, which has positive implication for clinical jaw reconstruction.
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- 2005
286. Towards an ideal polymer scaffold for tendon/ligament tissue engineering
- Author
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Sambit Sahoo, Hongwei Ouyang, James C.H. Goh, Siew Lok Toh, and Tong Earn Tay
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Scaffold ,business.product_category ,Materials science ,Biocompatibility ,Electrospinning ,Extracellular matrix ,PLGA ,chemistry.chemical_compound ,Tissue engineering ,chemistry ,Nanofiber ,Microfiber ,business ,Biomedical engineering - Abstract
Tissue engineering holds promise in treating injured tendons and ligaments by replacing the injured tissues with "engineered tissues" with identical mechanical and functional characteristics. A biocompatible, biodegradable, porous scaffold with optimized architecture, sufficient surface area for cell attachment, growth and proliferation, faborable mechanical properties, and suitable degradation rate is a pre-requisite to achieve success with this aproach. Knitted poly(lactide-co-glycolide) (PLGA) scaffolds comprising of microfibers of 25 micron diameter were coated with PLGA nanofibers on their surfaces by electrospinning technique. A cell suspension of pig bone marrow stromal cells (BMSC) was seeded on the scaffolds by pipetting, and the cell-scaffold constructs were cultured in a CO2 incubator, at 37°C for 1-2 weeks. The "engineered tissues" were then assessed for cell attachment and proliferation, tissue formation, and mechanical properties. Nanofibers, of diameter 300-900 nm, were spread randomly over the knitted scaffold. The reduction in pore-size from about 1 mm (in the knitted scaffold) to a few micrometers (in the nano-microscaffold) allowed cell seeding by direct pipetting, and eliminated the need of a cell-delivery system like fibrin gel. BMSCs were seen to attach and proliferate well on the nano-microscaffold, producing abundant extracellular matrix. Mechanical testing revealed that the cell-seeded nano-microscaffolds possessed slightly higher values of failure load, elastic-region stiffness and toe-region stiffness, than the unseeded scaffolds. The combination of superior mechanical strength and integrity of knitted microfibers, with the large surface area and improved hydrophilicity of the electrospun nanofibers facilitated cell attachment and new tissue formation. This holds promise in tissue engineering of tendon/ligament.© (2005) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
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- 2005
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287. Cyclic uniaxial strains on fibroblasts-seeded PLGA scaffolds for tissure engineering of ligaments
- Author
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Hongwei Ouyang, Kyaw Moe, James C.H. Goh, Tong Earn Tay, and Siew Lok Toh
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education.field_of_study ,Materials science ,Morphology (linguistics) ,Eosin ,Biocompatibility ,Strain (chemistry) ,Population ,Cell morphology ,chemistry.chemical_compound ,PLGA ,chemistry ,Tissue engineering ,Composite material ,education - Abstract
Mechanical strain regulates the structure and mechanical properties of the engineering tissue. Previous studies showed that cyclic mechanical strain affect in development and function of cells in tissue formation on various three-dimension scaffolds. In this study, the effect of cyclic uniaxial tensile straining on cell morphology was investigated. The objective of this research is to investigate the effect of cyclic uniaxial strain on cells' growth on knitted PLGA (Poly-Lactide-co-glycolide) scaffolds. A biocompatible cyclic uniaxial tensile straining device (bioreactor) was developed. Cyclic uniaxial straining was applied at 1.8% strain for 4 hours daily. To study the effect of cyclic frequency on cells' growth, two sets (1Hz and 0.1 Hz) of frequencies were used. After two weeks stimulation, the cell morphology was studied with the aid of Hematoxylin & Eosin staining using paraffin sectioning. In both frequency sets the mean nuclei length are longer than unstrained specimens. The cell population also tended to orientate parallel to the straining axis. In 0.1Hz frequency straining, more cell population are aligned in the straining direction than in 1Hz frequency. This study has demonstrated that cyclic uniaxial strain affect on cell morphology and mechanical properties of engineering tissue.
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- 2005
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288. Use of bone marrow stromal cells for tendon graft-to-bone healing: histological and immunohistochemical studies in a rabbit model
- Author
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Eng Hin Lee, Hongwei Ouyang, and James C.H. Goh
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Pathology ,medicine.medical_specialty ,Stromal cell ,Physical Therapy, Sports Therapy and Rehabilitation ,Bone healing ,Cell therapy ,Tendons ,03 medical and health sciences ,0302 clinical medicine ,New Zealand white rabbit ,medicine ,Animals ,Orthopedics and Sports Medicine ,Bone Marrow Transplantation ,030222 orthopedics ,Wound Healing ,biology ,business.industry ,Cartilage ,030229 sport sciences ,Anatomy ,biology.organism_classification ,Immunohistochemistry ,Tendon ,Hindlimb ,Calcaneus ,medicine.anatomical_structure ,Female ,Bone marrow ,Collagen ,Rabbits ,Stromal Cells ,Wound healing ,business - Abstract
Background Despite increasing attention on the issue of tendon-to-bone integration, there has been no animal study on the use of cell therapy for promoting the insertion healing of tendon to bone. Purpose To determine the efficacy of using a large number of bone marrow stromal cells (bMSCs) to enhance tendon-to-bone healing. Study Design Controlled laboratory study. Methods The hallucis longus tendons were translated into 2.5-mm diameter calcaneal bone tunnels in a New Zealand white rabbit model. The bone tunnels were treated with or without bMSCs. Three specimens from each group were harvested at 2, 4, and 6 weeks postoperatively and evaluated by conventional histological and immunohistochemical methods. Results At 4 weeks, the specimens with bMSCs exhibited more perpendicular collagen fiber formation and increased proliferation of cartilage-like cells, which was indicated by positive collagen type-II immuno-staining of the tendon-bone interface. In contrast, the specimens without bMSCs demonstrated progressive maturation and reorganization of fibrous tissue aligned along the load axis. Conclusion Introduction of a large number of bone marrow stromal cells to the bone tunnel have shown to improve the insertion healing of tendon to bone in a rabbit model through formation of fibrocartilagenous attachment at early time points.
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- 2004
289. 42 Inhibition Of Hif-2α Signalling With Digoxin Decreases Calcification In Tendinopathy
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Zi Yin, Jiajie Hu, Xiao Chen, and Hongwei Ouyang
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Achilles tendon ,Pathology ,medicine.medical_specialty ,biology ,business.industry ,CD44 ,Physical Therapy, Sports Therapy and Rehabilitation ,General Medicine ,medicine.disease ,Tendon ,medicine.anatomical_structure ,medicine ,biology.protein ,Alkaline phosphatase ,Orthopedics and Sports Medicine ,Progenitor cell ,Stem cell ,Tendinopathy ,business ,Calcification - Abstract
Introduction Chronic tendon pathology (tendinopathy) is a common but poorly treated disease, due to limited understanding of its pathogenesis. The resident tenocytes undergo continuous renewal form tendon progenitor/stem cells (TSPCs). 1 How TSPCs are maintained and differentiated into tenocytes in healthy individuals and which key molecular events are defective in patients have been largely unknown. Manipulating endogeous stem cells with small molecules has been proposed as a therapeutic strategy, but practical approaches are still unavailable. In this study, our results demonstrate that digoxin represents a potential approach for calcifying tendinopathy therapy through inhibiting HIF-2α mediated erroneous differentiation of TSPCs. Methods Human model of tendinopathy: Calcific Achilles tendon and supraspinatus tendon were collected from patients undergoing surgical procedures. Treatment: Digoxin/saline was injected into rat Achilles tendon subcutaneously every 3 days after collagenase injection. Results We compared the abundance of HIF-2α (encoded by EPAS1) in uncalcified and calcified regions of human and rat Achilles’s tendon. EPAS1 mRNA and protein levels were elevated in calcific tendons compared with normal tendons. Immunoreactive for stro-1, CD44 and HIF-2α demonstrated that HIF-2α was increased in TSPCs which located in the vicinity of calcific sites. These findings demostrate the HIF-2α level is increased in TSPCs of calcific tendons. Knockdown of HIF-2α by shRNA significantly decreased the activity of alkaline phosphatase (ALP) and Alizarin red staining (ARS) of human TSPCs underwent osteogenesis induction combined with IL1β treatment. In contrast, overexpression of a constitutive active form of HIF-2α lead to a significant reduction in expression levels of tendon specific markers, such as SCX, EYA1/2. These data suggest HIF-2α signalling plays a significant role in the fate specification of tenocytes and osteoblasts from TSPCs. Digoxin treatment in vitro inhibited IL1β-induced elevation of HIF-2α protein and significantly decreased the activity of ALP and ARS staining of TSPCs (Figure 1 a,b) and increased expression level of SCX, EYA1/2. Morever, we observed successful inhibition of HIF-2α in vivo by subcutaneously delivery of digoxin. X-ray quantification and histological examination showed that compared with vehicle, digoxin administration led to decreased calcium deposition (Figure 1 c,d). Discussion Our work provides a appicable therapeutic approach for tendon calcification, through manipulation of HIF-2α pathway in stem/progenitor cells by digoxin. I would like to apply for the British Journal of Sports Medicine Prize. Reference Bi Y, Ehirchiou D, Kilts TM, et al . Nat Med. 2007;13(10): 1219–27
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- 2014
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290. Wnt and Rho GTPase signaling in osteoarthritis development and intervention: implications for diagnosis and therapy
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Boon Chin Heng, Shouan Zhu, Hua Liu, Pengfei Chen, Huanhuan Liu, Yan Wu, and Hongwei Ouyang
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Cell physiology ,medicine.medical_specialty ,Pathology ,Immunology ,Chondrocyte hypertrophy ,Review ,GTPase ,Disease ,Bioinformatics ,Chondrocyte ,GTP Phosphohydrolases ,Chondrocytes ,Rheumatology ,Internal medicine ,Osteoarthritis ,medicine ,Animals ,Humans ,Immunology and Allergy ,Wnt Signaling Pathway ,Endochondral ossification ,business.industry ,Wnt signaling pathway ,medicine.anatomical_structure ,business ,Chondrogenesis - Abstract
Wnt and Rho GTPase signaling play critical roles in governing numerous aspects of cell physiology, and have been shown to be involved in endochondral ossification and osteoarthritis (OA) development. In this review, current studies of canonical Wnt signaling in OA development, together with the differential roles of Rho GTPases in chondrocyte maturation and OA pathology are critically summarized. Based on the current scientific literature together with our preliminary results, the strategy of targeting Wnt and Rho GTPase for OA prognosis and therapy is suggested, which is instructive for clinical treatment of the disease.
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- 2013
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291. Inhibitory function of parathyroid hormone-related protein on chondrocyte hypertrophy: the implication for articular cartilage repair
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Wei Zhang, Hongwei Ouyang, Jialin Chen, and Shufang Zhang
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musculoskeletal diseases ,Cartilage, Articular ,medicine.medical_specialty ,Immunology ,Chondrocyte hypertrophy ,Osteoarthritis ,Review ,Chondrocytes ,Rheumatology ,Internal medicine ,medicine ,Articular cartilage repair ,Immunology and Allergy ,Animals ,Humans ,Endochondral ossification ,Parathyroid hormone-related protein ,business.industry ,Cartilage ,Mesenchymal stem cell ,Parathyroid Hormone-Related Protein ,Hyperostosis ,Chondrogenesis ,medicine.disease ,musculoskeletal system ,Endocrinology ,medicine.anatomical_structure ,Cancer research ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Cartilage repair tissue is usually accompanied by chondrocyte hypertrophy and osseous overgrowths, and a role for parathyroid hormone-related protein (PTHrP) in inhibiting chondrocytes from hypertrophic differentiation during the process of endochondral ossification has been demonstrated. However, application of PTHrP in cartilage repair has not been extensively considered. This review systemically summarizes for the first time the inhibitory function of PTHrP on chondrocyte hypertrophy in articular cartilage and during the process of endochondral ossification, as well as the process of mesenchymal stem cell chondrogenic differentiation. Based on the literature review, the strategy of using PTHrP for articular cartilage repair is suggested, which is instructive for clinical treatment of cartilage injuries as well as osteoarthritis.
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- 2012
292. The evaluation of a novel bone marrow stem cell based silk sling on rat model of stress urinary incontinence
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Lin-Lin Wang, Yi Ying Qi, Xiaohui Zou, Xiao Chen, Hang Mei Jin, and Hongwei Ouyang
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medicine.medical_specialty ,Sling (implant) ,fungi ,Rat model ,technology, industry, and agriculture ,Urology ,Bone Marrow Stem Cell ,Urinary incontinence ,macromolecular substances ,Cell Biology ,Anatomy ,Biology ,equipment and supplies ,medicine ,medicine.symptom ,Molecular Biology - Abstract
The evaluation of a novel bone marrow stem cell based silk sling on rat model of stress urinary incontinence
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- 2008
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293. Clinical translation of autologous cell-based tissue engineering techniques as Class III therapeutics in China: Taking cartilage tissue engineering as an example
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Wei Zhang, Yangzi Jiang, Boon Chin Heng, and Hongwei Ouyang
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medicine.medical_specialty ,Autologous cell ,Transplantation surgery ,lcsh:Diseases of the musculoskeletal system ,Tissue engineering techniques ,business.industry ,Process (engineering) ,Clinical translation ,Translational medicine ,Class iii ,Autologous cells ,Cartilage tissue engineering ,Surgery ,Tissue engineering ,medicine ,Orthopedics and Sports Medicine ,Medical physics ,lcsh:RC925-935 ,business - Abstract
Summary Autologous cell-based tissue engineering (TE) techniques have been clinically approved for approximately 4 years in China, since the first cartilage TE technique was approved for clinical use by the Zhejiang Health Bureau. TE techniques offer a promising alternative to traditional transplantation surgery, and are different from those for transplanted tissues (biologics or pharmaceutical), the clinical translational procedures are unique and multitasked, and the requirements may differ from those of the target tissues. Thus, the translational procedure is still unfamiliar to most researchers and needs further improvement. This perspectives paper describes the key guidelines and regulations involved in the current translational process, and shares our translational experiences in cartilage TE to provide an example of autologous cell-based TE translation in China. Finally, we discuss the scientific and social challenges and provide some suggestions for future improvements.
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294. An Off-the-Shelf Tissue Engineered Cartilage Composed of Optimally Sized Pellets of Cartilage Progenitor/Stem Cells
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Zi Yin, Zefeng Zheng, Jisheng Ran, Yang Fei, Weiliang Shen, lidong wu, Hongwei Ouyang, Chenqi Tang, Boon Chin Heng, Dengfeng Ruan, Jiayun Huang, Dominique P. Pioletti, Lingfang Shen, Yejun Hu, Yangwu Chen, Xiao Chen, and Canlong Wang
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Cartilage, Articular ,Pathology ,medicine.medical_specialty ,education ,0206 medical engineering ,Biomedical Engineering ,mesenchymal stem-cells ,cartilage defect repair ,knee ,Articular cartilage ,Tissue engineered cartilage ,02 engineering and technology ,hepatocyte spheroids ,Biomaterials ,Chondrocytes ,Tissue engineering ,medicine ,articular-cartilage ,Humans ,Off the shelf ,Autologous chondrocyte implantation ,defects ,Progenitor ,business.industry ,Stem Cells ,Cartilage ,differentiation ,021001 nanoscience & nanotechnology ,pellets ,020601 biomedical engineering ,culture ,medicine.anatomical_structure ,tissue engineering ,repair ,regeneration ,Stem cell ,cartilage stem/progenitor cells (cspcs) ,0210 nano-technology ,business ,autologous chondrocyte implantation ,Chondrogenesis - Abstract
Articular cartilage focal lesion remains an intractable challenge in sports medicine, and autologous chondrocytes' implantation (ACI) is one of the most commonly utilized treatment modality for this ailment. However, the current ACI technique requires two surgical steps which increases patients' morbidity and incurs additional medical costs. In the present study, we developed a one-step cryopreserved off-the-shelf ACI tissue-engineered (TE) cartilage by seeding pellets of spheroidal cartilage stem/progenitor cells (CSPCs) on a silk scaffold. The pellets were developed through a hanging-drop method, and the incubation time of 1 day could efficiently produce spheroidal pellets without any adverse influence on the cell activity. The pellet size was also optimized. Under chondrogenic induction, pellets consisting of 40 000 CSPCs were found to exhibit the most abundant cartilage matrix deposition and the highest mRNA expression levels of SOX9, aggrecan, and COL2A1, as compared with pellets consisting of 10 000, 100 000, or 200 000 CSPCs. Scaffolds seeded with CSPCs pellets containing 40 000 cells could be preserved in liquid nitrogen with the viability, migration, and chondrogenic ability remaining unaffected for as long as 3 months. When implanted in a rat trochlear cartilage defect model for 3 months, the ready-to-use, cryopreserved TE cartilage yielded fully cartilage reconstruction, which was comparable with the uncryopreserved control. Hence, our study provided preliminary data that our off-the-shell TE cartilage with optimally sized CSPCs pellets seeded within silk scaffolds exhibited strong cartilage repair capacity, which provided a convenient and promising one-step surgical approach to ACI.
295. Intra-articular Injection Of ACL-derived Stem Cells Combined With Silk-Collagen Scaffold for Anterior Cruciate Ligament Reconstruction
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Jisheng Ran, Long Yang, Yejun Hu, Ting Zhu, Zefeng Zheng, Zi Yin, Hongwei Ouyang, Weiliang Shen, Junjuan Wang, and Xiao Chen
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lcsh:Diseases of the musculoskeletal system ,Anterior cruciate ligament reconstruction ,Chemistry ,medicine.medical_treatment ,02 engineering and technology ,Anatomy ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Intra articular ,SILK ,medicine ,Orthopedics and Sports Medicine ,lcsh:RC925-935 ,0210 nano-technology ,Collagen scaffold - Full Text
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296. Directing tenogenesis of stem cells with small molecule-based nanofibers
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Erchen Zhang, Yip Yio Chin, Hongwei Ouyang, Xiao Chen, Can Zhang, and Li Dak Sum
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lcsh:Diseases of the musculoskeletal system ,Chemistry ,Nanofiber ,Biophysics ,Orthopedics and Sports Medicine ,lcsh:RC925-935 ,Stem cell ,Small molecule - Full Text
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297. Targeted pathological collagen delivery of sustained-release rapamycin to prevent heterotopic ossification.
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Yangwu Chen, Weiliang Shen, Chenqi Tang, Jiayun Huang, Chunmei Fan, Zi Yin, Yejun Hu, Weishan Chen, Hongwei Ouyang, Yiting Zhou, Zhengwei Mao, and Xiao Chen
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HETEROTOPIC ossification , *DRUG coatings , *COLLAGEN , *ANTERIOR cruciate ligament surgery , *CIRCULAR RNA - Abstract
The article discusses a study on targeted pathological collagen delivery of sustained-release rapamycin to prevent heterotopic ossification. It mentions that tendon stem/ progenitor cells do not undergo osteochondrogenic differentiation when mTOR signaling is inactivated by gene knockout or rapamycin (RAPA) treatment.
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- 2020
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298. Biomimetic photo-responsive hydrogels for articular cartilage defects repair
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Ma, Yuanzhu, Shipston, Michael, Bachmann, Till, and Hongwei Ouyang
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tissue engineering ,cartilage repair ,3D printing ,hydrogels ,biomaterials - Abstract
Osteoarthritis (OA) is one of the most prevalent chronic diseases and severely impacts the quality of patients’ life and brings burdens to society. Cartilage defects are important pathological features of OA. Challenges remain in both partial-thickness cartilage defects and osteochondral defects: it is difficult to fix the materials used for partial-thickness cartilage defects and the scaffolds for osteochondral defects require high performance in biological properties as well as structural properties. As a three-dimensional polymer network containing a large amount of water, hydrogels have become widespread in cartilage repair and other biomedical applications for their biomimetic properties and multifunctionalities. Here, based on the cartilage matrix, biomimetic hydrogels for articular cartilage defects repairment were developed. For partial-thickness cartilage defects, a two-step biomimetic adhesive hydrogel was developed; besides, a one-step adhesive hydrogel was developed by improving the components design of the previous strategy; for osteochondral defects, high-precision 3D hydrogel bioprinting system was developed for the preparation of biomimetic scaffolds. The research mainly includes the following contents: 1. ‘Two-step’ photo-responsive biomimetic tissue-adhesive hydrogel for partial-thickness cartilage defect repair. Partial-thickness cartilage defect is the most common symptom of OA but till now it is less focused with no proven clinical treatments and relatively less research on partial-thickness cartilage defect repair. Mimicking the natural cartilage, the tissue adhesive hydrogel “joint paint” is comprised of a gelatin methacrylate (GelMA)/ hyaluronic acid (HA) surface layer and a chondroitin sulfate (CS) layer that can bridge the surface layer and the cartilage. The joint paint can rapidly gel at the defect area under light exposure and the formed binding is tight enough for long-term maintenance. Being able to keep main cartilage matrix components such as glycosaminoglycan and inhibit cell apoptosis, this hydrogel functions well in rabbit partial-thickness cartilage defect models with good tissue integration and regeneration capability. 2. One-step photoresponsive biomimetic tissue adhesive hydrogel for partial-thickness cartilage defect repair Based on the strategy of in situ photoresponsive adhesive hydrogels for partial-thickness cartilage defects repairment, the material formulation was improved to avoid the two-step usage in Chapter 3, making it more suitable for clinical application and translation. The photoinduced imine crosslinking strategy was used to provide the adhesion ability between hydrogels and tissues. O-nitrobenzyl compound NB was grafted onto CS, and hydrogels containing GelMA, CSNB, and HA were prepared according to the proportion of natural cartilage matrix components. This double-network hydrogel can gel rapidly on cartilage surface in a single step and shows good efficacy for partial-thickness cartilage defects regeneration in large animal models. 3. High precision stereolithography 3D bioprinting system for the preparation of osteochondral tissue engineering scaffolds with biomimetic structure Osteochondral defect is one of the manifestations of the terminal progression of osteoarthritis. Structure-free hydrogels cannot meet the needs of osteochondral defect repair. However, due to technical limitations, the current osteochondral tissue engineering scaffolds rarely improve their performance through structures. 3D printing technology is a powerful means of creating complex structures. The application of CSNB in stereolithography 3D printing solves the problem that the printing resolution, the mechanical properties of products, and the cell-laden ability cannot be achieved simultaneously in the current 3D bioprinting technologies. CSNB system was used to print osteochondral scaffolds with a tidemark structure that could disperse mechanical load and the in vivo repair function of the scaffolds was assessed.
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- 2022
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