Osteoarthritis （OA）, identified as one of the priorities for the Bone and Joint Decade, is one of the most prevalent joint diseases, which causes pain and disability of joints in the adult population. Secondary OA u...Osteoarthritis （OA）, identified as one of the priorities for the Bone and Joint Decade, is one of the most prevalent joint diseases, which causes pain and disability of joints in the adult population. Secondary OA usually stems from repetitive overloading to the osteochondral （OC） unit, which could result in cartilage damage and changes in the subchondral bone, leading to mechanical instability of the joint and loss of joint function. Tissue engineering approaches have emerged for the repair of cartilage defects and damages to the subchondral bone in the early stages of OA and have shown potential in restoring the joint＇s function. In this approach, the use of three-dimensional scaffolds （with or without cells） provides support for tissue growth. Commercially available OC scaffolds have been studied in OA patients for repair and regeneration of OC defects. However, none of these scaffolds has shown satisfactory clinical results. This article reviews the OC tissue structure and the design, manufacturing and performance of current OC scaffolds in treatment of OA. The findings demonstrate the importance of biological and biomechanical fixations of OC scaffolds to the host tissue in achieving an improved cartilage fill and a hyaline-like tissue formation. Achieving a strong and stable subchondral bone support that helps the regeneration of overlying cartilage seems to be still a grand challenge for the early treatment of OA.展开更多
Osteochondral （OC） lesions are characterized by defects in two different zones, the cartilage region and subchondral bone region. These lesions are frequently associated with mechanical instability, as well as osteo...Osteochondral （OC） lesions are characterized by defects in two different zones, the cartilage region and subchondral bone region. These lesions are frequently associated with mechanical instability, as well as osteoarthritic degenerative changes in the knee. The lack of spontaneous healing and the drawbacks of the current treatments have increased the attention from the scientific community to this issue. Different tissue engineering approaches have been attempted using different polymers and different scaffolds＇ processing. However, the current conventional techniques do not allow the full control over scaffold fabrication, and in this type of approaches, the tuning ability is the key to success in tissue regeneration. In this sense, the researchers have placed their efforts in the development of solid free-form （SFF） techniques. These techniques allow tuning different properties at the micro-macro scale, creating scaffolds with appropriate features for OC tissue engineering. In this review, it is discussed the current SFF techniques used in OC tissue engineering and presented their promising results and current challenges.展开更多
Textile-based technologies are considered as potential routes for the production of 3D porous architectures for tissue engineering( TE) applications. We describe the use of two polymers,namely polybutylene succinate( ...Textile-based technologies are considered as potential routes for the production of 3D porous architectures for tissue engineering( TE) applications. We describe the use of two polymers,namely polybutylene succinate( PBS) and silk fibroin(SF) to produce fiber-based finely tuned porous architectures by weft and warp knittings. The obtained knitted constructs are described in terms of their morphology, mechanical properties,swelling ability,degradation behaviour,and cytotoxicity. Each type of polymer fibers allows for the processing of a very reproducible intra-architectural scaffold geometry,with distinct characteristics in terms of the surface physicochemistry,mechanical performance,and degradation capability,which has an impact on the resulting cell behaviour at the surface of the respective biotextiles. Preliminary cytotoxicity screening shows that both materials can support cell adhesion and proliferation. Furthermore, different surface modifications were performed( acid /alkaline treatment, UV radiation,and plasma) for modulating cell behavior. An increase of cell-material interactions were observed,indicating the important role of materials surface in the first hours of culturing. Human adipose-derived stem cells( hASCs) became an emerging possibility for regenerative medicine and tissue replacement therapies. The potential of the recently developed silk-based biotextile structures to promote hASCs adhesion,proliferation,and differentiation is also evaluated. The obtained results validate the developed constructs as viable matrices for TE applications. Given the processing efficacy and versatility of the knitting technology, and the interesting structural and surface properties of the proposed polymer fibers,it is foreseen that our developed systems can be attractive for the functional engineering of tissues such as bone,skin,ligaments or cartilage and also for develop more complex systems for further industrialization of TE products.展开更多
In spite of the considerable achievements in the field of regenerative medicine in the past several decades,osteochondral defect regeneration remains a challenging issue among diseases in the musculoskeletal system be...In spite of the considerable achievements in the field of regenerative medicine in the past several decades,osteochondral defect regeneration remains a challenging issue among diseases in the musculoskeletal system because of the spatial complexity of osteochondral units in composition,structure and functions.In order to repair the hierarchical tissue involving different layers of articular cartilage,cartilage-bone interface and subchondral bone,traditional clinical treatments including palliative and reparative methods have showed certain improvement in pain relief and defect filling.It is the development of tissue engineering that has provided more promising results in regenerating neo-tissues with comparable compositional,structural and functional characteristics to the native osteochondral tissues.Here in this review,some basic knowledge of the osteochondral units including the anatomical structure and composition,the defect classification and clinical treatments will be first introduced.Then we will highlight the recent progress in osteochondral tissue engineering from perspectives of scaffold design,cell encapsulation and signaling factor incorporation including bioreactor application.Clinical products for osteochondral defect repair will be analyzed and summarized later.Moreover,we will discuss the current obstacles and future directions to regenerate the damaged osteochondral tissues.展开更多
Poly(lactide-co-glycolide)-bilayered scaffolds with the same porosity or different ones on the two layers were fabricated,and the porosity effect on in vivo repairing of the osteochondral defect was examined in a comp...Poly(lactide-co-glycolide)-bilayered scaffolds with the same porosity or different ones on the two layers were fabricated,and the porosity effect on in vivo repairing of the osteochondral defect was examined in a comparative way for the first time.The constructs of scaffolds and bone marrow-derived mesenchymal stem cells were implanted into pre-created osteochondral defects in the femoral condyle of New Zealand white rabbits.After 12 weeks,all experimental groups exhibited good cartilage repairing according to macroscopic appearance,cross-section view,haematoxylin and eosin staining,toluidine blue staining,immunohistochemical staining and real-time polymerase chain reaction of characteristic genes.The group of 92%porosity in the cartilage layer and 77%porosity in the bone layer resulted in the best efficacy,which was understood by more biomechanical mimicking of the natural cartilage and subchondral bone.This study illustrates unambiguously that cartilage tissue engineering allows for a wide range of scaffold porosity,yet some porosity group is optimal.It is also revealed that the biomechanical matching with the natural composite tissue should be taken into consideration in the design of practical biomaterials,which is especially important for porosities of a multi-compartment scaffold concerning connected tissues.展开更多
The osteochondral defect repair has been most extensively studied due to the rising demand for new therapies to diseases such as osteoarthritis.Tissue engineering has been proposed as a promising strategy to meet the ...The osteochondral defect repair has been most extensively studied due to the rising demand for new therapies to diseases such as osteoarthritis.Tissue engineering has been proposed as a promising strategy to meet the demand of simultaneous regeneration of both cartilage and subchondral bone by constructing integrated gradient tissue-engineered osteochondral scaffold(IGTEOS).This review brought forward the main challenges of establishing a satisfactory IGTEOS from the perspectives of the complexity of physiology and microenvironment of osteochondral tissue,and the limitations of obtaining the desired and required scaffold.Then,we comprehensively discussed and summarized the current tissue-engineered efforts to resolve the above challenges,including architecture strategies,fabrication techniques and in vitro/in vivo evaluation methods of the IGTEOS.Especially,we highlighted the advantages and limitations of various fabrication techniques of IGTEOS,and common cases of IGTEOS application.Finally,based on the above challenges and current research progress,we analyzed in details the future perspectives of tissue-engineered osteochondral construct,so as to achieve the perfect reconstruction of the cartilaginous and osseous layers of osteochondral tissue simultaneously.This comprehensive and instructive review could provide deep insights into our current understanding of IGTEOS.展开更多
Osteochondral lesion repair is a challenging area of orthopedic surgery. Here we aimed to develop an extracellular matrix-derived, integrated, biphasic scaffold and to investigate the regeneration potential of the sca...Osteochondral lesion repair is a challenging area of orthopedic surgery. Here we aimed to develop an extracellular matrix-derived, integrated, biphasic scaffold and to investigate the regeneration potential of the scaffold loaded with chondrogenically-induced bone marrow-derived mesenchymal stem cells （BMSCs） in the repair of a large, high-load-bearing, osteochondral defect in a canine model. Methods The biphasic scaffolds were fabricated by combining a decellularization procedure with a freeze-drying technique and characterized by scanning electron microscopy （SEM） and micro-computed tomography （micro-CT）. Osteochondral constructs were fabricated in vitro using chondrogenically-induced BMSCs and a biphasic scaffold, then assessed by SEM for cell attachment. Osteochondral defects （4.2 mm （diameter） ×6 mm （depth）） were created in canine femoral condyles and treated with a construct of the biphasic scaffold/chondrogenically-induced BMSCs or with a cell-free scaffold （control group）. The repaired defects were evaluated for gross morphology and by histological, biochemical, biomechanical and micro-CT analyses at 3 and 6 months post-implantation. Results The osteochondral defects of the experimental group showed better repair than those of the control group. Statistical analysis demonstrated that the macroscopic and histologic grading scores of the experimental group were always higher than those of the control group, and that the scores for the experimental group at 6 months were significantly higher than those at 3 months. The cartilage stiffness in the experimental group （6 months） was （6.95±0.79） N/mm, 70.77% of normal cartilage; osteochondral bone stiffness in the experimental group was （158.16±24.30） N/mm, 74.95% of normal tissue; glycosaminoglycan content of tissue-engineered neocartilage was （218±21.6） tJg/mg （dry weight）, 84.82% of native cartilage. Micro-CT analysis of the subchondral bone showed mature trabecular bone regularly formed at 3 and 6 months, with no significant difference between the experimental and control groups. Conclusion The extracellular matrix-derived, integrated, biphasic scaffold shows potential for the repair of large, high-load-bearing osteochondral defects.展开更多
Osteochondral defects are caused by injury to both the articular cartilage and subchondral bone within skeletal joints. They can lead to irreversible joint damage and increase the risk of progression to osteoarthritis...Osteochondral defects are caused by injury to both the articular cartilage and subchondral bone within skeletal joints. They can lead to irreversible joint damage and increase the risk of progression to osteoarthritis. Current treatments for osteochondral injuries are not curative and only target symptoms, highlighting the need for a tissue engineering solution. Scaffold-based approaches can be used to assist osteochondral tissue regeneration, where biomaterials tailored to the properties of cartilage and bone are used to restore the defect and minimise the risk of further joint degeneration. This review captures original research studies published since 2015, on multiphasic scaffolds used to treat osteochondral defects in animal models. These studies used an extensive range of biomaterials for scaffold fabrication, consisting mainly of natural and synthetic polymers. Different methods were used to create multiphasic scaffold designs, including by integrating or fabricating multiple layers, creating gradients, or through the addition of factors such as minerals, growth factors, and cells. The studies used a variety of animals to model osteochondral defects, where rabbits were the most commonly chosen and the vast majority of studies reported small rather than large animal models. The few available clinical studies reporting cell-free scaffolds have shown promising early-stage results in osteochondral repair, but long-term follow-up is necessary to demonstrate consistency in defect restoration. Overall, preclinical studies of multiphasic scaffolds show favourable results in simultaneously regenerating cartilage and bone in animal models of osteochondral defects, suggesting that biomaterials-based tissue engineering strategies may be a promising solution.展开更多
The osteochondral defects caused by vigorous trauma or physical disease are difficult to be managed.Tissue engineering provides a possible option to regenerate the damaged osteochondral tissues.For osteochondral recon...The osteochondral defects caused by vigorous trauma or physical disease are difficult to be managed.Tissue engineering provides a possible option to regenerate the damaged osteochondral tissues.For osteochondral reconstruction,one intact scaffold should be considered to support the regeneration of both cartilage and subchondral bone.Therefore,the biphasic scaffolds with the mimic structures of osteochondral tissues have been developed to close this chasm.A variety of biomimetic bilayer scaffolds fabricated from natural or synthetic polymers,or the ones loading with growth factors,cells,or both of them make great progresses in osteochondral defect repair.In this review,the preparation and in vitro and/or in vivo verification of bioinspired biphasic scaffolds are summarized and discussed,as well as the prospect is predicted.展开更多
Autologous mosaicplasty is a common approach used to treat osteochondral defects in clinical practice.Gap integration between host and transplanted plugs requires bone tissue reservation and hyaline cartilage regenera...Autologous mosaicplasty is a common approach used to treat osteochondral defects in clinical practice.Gap integration between host and transplanted plugs requires bone tissue reservation and hyaline cartilage regeneration without uneven surface,graft necrosis and sclerosis.However,poor gap integration is a serious concern,which eventually leads to deterioration of joint function.To deal with such complications,this study has developed a strategy to effectively enhance integration of the gap region following mosaicplasty by applying injectable bioactive supramolecular nanofiber-enabled gelatin methacryloyl(GelMA)hydrogel(BSN-GelMA).A rabbit osteochondral defect model demonstrated that BSN-GelMA achieved seamless osteochondral healing in the gap region between plugs of osteochondral defects following mosaicplasty,as early as six weeks.Moreover,the International Cartilage Repair Society score,histology score,glycosaminoglycan content,subchondral bone volume,and collagen II expression were observed to be the highest in the gap region of BSN-GelMA treated group.This improved outcome was due to bio-interactive materials,which acted as tissue fillers to bridge the gap,prevent cartilage degeneration,and promote graft survival and migration of bone marrow mesenchymal stem cells by releasing bioactive supramolecular nanofibers from the GelMA hydrogel.This study provides a powerful and applicable approach to improve gap integration after autologous mosaicplasty.It is also a promising off-the-shelf bioactive material for cell-free in situ tissue regeneration.展开更多
Osteoarthritis is a degenerative joint disease,typified by the loss in the quality of cartilage and bone at the interface of a synovial joint,resulting in pain,stiffness and reduced mobility.The current surgical treat...Osteoarthritis is a degenerative joint disease,typified by the loss in the quality of cartilage and bone at the interface of a synovial joint,resulting in pain,stiffness and reduced mobility.The current surgical treatment for advanced stages of the disease is joint replacement,where the non-surgical therapeutic options or less invasive surgical treatments are no longer effective.These are major surgical procedures which have a substantial impact on patients’quality of life and lifetime risk of requiring revision surgery.Treatments using regenerative methods such as tissue engineering methods have been established and are promising for the early treatment of cartilage degeneration in osteoarthritis joints.In this approach,3-dimensional scaffolds(with or without cells)are employed to provide support for tissue growth.However,none of the currently available tissue engineering and regenerative medicine products promotes satisfactory durable regeneration of large cartilage defects.Herein,we discuss the current regenerative treatment options for cartilage and osteochondral(cartilage and underlying subchondral bone)defects in the articulating joints.We further identify the main hurdles in osteochondral scaffold development for achieving satisfactory and durable regeneration of osteochondral tissues.The evolution of the osteochondral scaffolds–from monophasic to multiphasic constructs–is overviewed and the osteochondral scaffolds that have progressed to clinical trials are examined with respect to their clinical performances and their potential impact on the clinical practices.Development of an osteochondral scaffold which bridges the gap between small defect treatment and joint replacement is still a grand challenge.Such scaffold could be used for early treatment of cartilage and osteochondral defects at early stage of osteoarthritis and could either negate or delay the need for joint replacements.展开更多
文摘Osteoarthritis （OA）, identified as one of the priorities for the Bone and Joint Decade, is one of the most prevalent joint diseases, which causes pain and disability of joints in the adult population. Secondary OA usually stems from repetitive overloading to the osteochondral （OC） unit, which could result in cartilage damage and changes in the subchondral bone, leading to mechanical instability of the joint and loss of joint function. Tissue engineering approaches have emerged for the repair of cartilage defects and damages to the subchondral bone in the early stages of OA and have shown potential in restoring the joint＇s function. In this approach, the use of three-dimensional scaffolds （with or without cells） provides support for tissue growth. Commercially available OC scaffolds have been studied in OA patients for repair and regeneration of OC defects. However, none of these scaffolds has shown satisfactory clinical results. This article reviews the OC tissue structure and the design, manufacturing and performance of current OC scaffolds in treatment of OA. The findings demonstrate the importance of biological and biomechanical fixations of OC scaffolds to the host tissue in achieving an improved cartilage fill and a hyaline-like tissue formation. Achieving a strong and stable subchondral bone support that helps the regeneration of overlying cartilage seems to be still a grand challenge for the early treatment of OA.
文摘Osteochondral （OC） lesions are characterized by defects in two different zones, the cartilage region and subchondral bone region. These lesions are frequently associated with mechanical instability, as well as osteoarthritic degenerative changes in the knee. The lack of spontaneous healing and the drawbacks of the current treatments have increased the attention from the scientific community to this issue. Different tissue engineering approaches have been attempted using different polymers and different scaffolds＇ processing. However, the current conventional techniques do not allow the full control over scaffold fabrication, and in this type of approaches, the tuning ability is the key to success in tissue regeneration. In this sense, the researchers have placed their efforts in the development of solid free-form （SFF） techniques. These techniques allow tuning different properties at the micro-macro scale, creating scaffolds with appropriate features for OC tissue engineering. In this review, it is discussed the current SFF techniques used in OC tissue engineering and presented their promising results and current challenges.
文摘Textile-based technologies are considered as potential routes for the production of 3D porous architectures for tissue engineering( TE) applications. We describe the use of two polymers,namely polybutylene succinate( PBS) and silk fibroin(SF) to produce fiber-based finely tuned porous architectures by weft and warp knittings. The obtained knitted constructs are described in terms of their morphology, mechanical properties,swelling ability,degradation behaviour,and cytotoxicity. Each type of polymer fibers allows for the processing of a very reproducible intra-architectural scaffold geometry,with distinct characteristics in terms of the surface physicochemistry,mechanical performance,and degradation capability,which has an impact on the resulting cell behaviour at the surface of the respective biotextiles. Preliminary cytotoxicity screening shows that both materials can support cell adhesion and proliferation. Furthermore, different surface modifications were performed( acid /alkaline treatment, UV radiation,and plasma) for modulating cell behavior. An increase of cell-material interactions were observed,indicating the important role of materials surface in the first hours of culturing. Human adipose-derived stem cells( hASCs) became an emerging possibility for regenerative medicine and tissue replacement therapies. The potential of the recently developed silk-based biotextile structures to promote hASCs adhesion,proliferation,and differentiation is also evaluated. The obtained results validate the developed constructs as viable matrices for TE applications. Given the processing efficacy and versatility of the knitting technology, and the interesting structural and surface properties of the proposed polymer fibers,it is foreseen that our developed systems can be attractive for the functional engineering of tissues such as bone,skin,ligaments or cartilage and also for develop more complex systems for further industrialization of TE products.
基金This work was supported by grants from the National Natural Science Foundation of China(No.51772233)the National Key Research and Development Program of China(2018YFB1105500)+3 种基金the Major Special Projects of Technological Innovation of Hubei Province(No.2019ACA130)the Application Foundation and Front Research Program of Wuhan(No.2018010401011273)Foshan Xianhu Laboratory of the Advanced Energy Science and Technology Guangdong Laboratory(XHT2020-008)the Fundamental Research Funds for the Central Universities(2020-YB-015).
文摘In spite of the considerable achievements in the field of regenerative medicine in the past several decades,osteochondral defect regeneration remains a challenging issue among diseases in the musculoskeletal system because of the spatial complexity of osteochondral units in composition,structure and functions.In order to repair the hierarchical tissue involving different layers of articular cartilage,cartilage-bone interface and subchondral bone,traditional clinical treatments including palliative and reparative methods have showed certain improvement in pain relief and defect filling.It is the development of tissue engineering that has provided more promising results in regenerating neo-tissues with comparable compositional,structural and functional characteristics to the native osteochondral tissues.Here in this review,some basic knowledge of the osteochondral units including the anatomical structure and composition,the defect classification and clinical treatments will be first introduced.Then we will highlight the recent progress in osteochondral tissue engineering from perspectives of scaffold design,cell encapsulation and signaling factor incorporation including bioreactor application.Clinical products for osteochondral defect repair will be analyzed and summarized later.Moreover,we will discuss the current obstacles and future directions to regenerate the damaged osteochondral tissues.
基金This work was supported by Chinese Ministry of Science and Technology(973 Programs No.2009CB930000 and No.2011CB606203)National Science Foundation of China(Grant No.21034002,31170925,and 51273046)+1 种基金Science and Technology Developing Foundation of Shanghai(Grant No.13XD1401000)Shanghai International Science and Technology Partnership Program(No.11540702700).
文摘Poly(lactide-co-glycolide)-bilayered scaffolds with the same porosity or different ones on the two layers were fabricated,and the porosity effect on in vivo repairing of the osteochondral defect was examined in a comparative way for the first time.The constructs of scaffolds and bone marrow-derived mesenchymal stem cells were implanted into pre-created osteochondral defects in the femoral condyle of New Zealand white rabbits.After 12 weeks,all experimental groups exhibited good cartilage repairing according to macroscopic appearance,cross-section view,haematoxylin and eosin staining,toluidine blue staining,immunohistochemical staining and real-time polymerase chain reaction of characteristic genes.The group of 92%porosity in the cartilage layer and 77%porosity in the bone layer resulted in the best efficacy,which was understood by more biomechanical mimicking of the natural cartilage and subchondral bone.This study illustrates unambiguously that cartilage tissue engineering allows for a wide range of scaffold porosity,yet some porosity group is optimal.It is also revealed that the biomechanical matching with the natural composite tissue should be taken into consideration in the design of practical biomaterials,which is especially important for porosities of a multi-compartment scaffold concerning connected tissues.
基金support from the National Natural Science Foundation of China(No.32171345)Hebei Provincial Natural Science Foundation of China(No.C2022104003)+2 种基金the Fok Ying Tung Education Foundation(No.141039)the Fund of Key Laboratory of Advanced Materials of Ministry of Education,the International Joint Research Center of Aerospace Biotechnology and Medical Engineering,Ministry of Science and Technology of Chinathe 111 Project(No.B13003).
文摘The osteochondral defect repair has been most extensively studied due to the rising demand for new therapies to diseases such as osteoarthritis.Tissue engineering has been proposed as a promising strategy to meet the demand of simultaneous regeneration of both cartilage and subchondral bone by constructing integrated gradient tissue-engineered osteochondral scaffold(IGTEOS).This review brought forward the main challenges of establishing a satisfactory IGTEOS from the perspectives of the complexity of physiology and microenvironment of osteochondral tissue,and the limitations of obtaining the desired and required scaffold.Then,we comprehensively discussed and summarized the current tissue-engineered efforts to resolve the above challenges,including architecture strategies,fabrication techniques and in vitro/in vivo evaluation methods of the IGTEOS.Especially,we highlighted the advantages and limitations of various fabrication techniques of IGTEOS,and common cases of IGTEOS application.Finally,based on the above challenges and current research progress,we analyzed in details the future perspectives of tissue-engineered osteochondral construct,so as to achieve the perfect reconstruction of the cartilaginous and osseous layers of osteochondral tissue simultaneously.This comprehensive and instructive review could provide deep insights into our current understanding of IGTEOS.
基金the grants from the National Science Foundation of China，the Research Foundation of the Tianjin Health Bureau
文摘Osteochondral lesion repair is a challenging area of orthopedic surgery. Here we aimed to develop an extracellular matrix-derived, integrated, biphasic scaffold and to investigate the regeneration potential of the scaffold loaded with chondrogenically-induced bone marrow-derived mesenchymal stem cells （BMSCs） in the repair of a large, high-load-bearing, osteochondral defect in a canine model. Methods The biphasic scaffolds were fabricated by combining a decellularization procedure with a freeze-drying technique and characterized by scanning electron microscopy （SEM） and micro-computed tomography （micro-CT）. Osteochondral constructs were fabricated in vitro using chondrogenically-induced BMSCs and a biphasic scaffold, then assessed by SEM for cell attachment. Osteochondral defects （4.2 mm （diameter） ×6 mm （depth）） were created in canine femoral condyles and treated with a construct of the biphasic scaffold/chondrogenically-induced BMSCs or with a cell-free scaffold （control group）. The repaired defects were evaluated for gross morphology and by histological, biochemical, biomechanical and micro-CT analyses at 3 and 6 months post-implantation. Results The osteochondral defects of the experimental group showed better repair than those of the control group. Statistical analysis demonstrated that the macroscopic and histologic grading scores of the experimental group were always higher than those of the control group, and that the scores for the experimental group at 6 months were significantly higher than those at 3 months. The cartilage stiffness in the experimental group （6 months） was （6.95±0.79） N/mm, 70.77% of normal cartilage; osteochondral bone stiffness in the experimental group was （158.16±24.30） N/mm, 74.95% of normal tissue; glycosaminoglycan content of tissue-engineered neocartilage was （218±21.6） tJg/mg （dry weight）, 84.82% of native cartilage. Micro-CT analysis of the subchondral bone showed mature trabecular bone regularly formed at 3 and 6 months, with no significant difference between the experimental and control groups. Conclusion The extracellular matrix-derived, integrated, biphasic scaffold shows potential for the repair of large, high-load-bearing osteochondral defects.
基金support from the National Health and Medical Research Council(NHMRC)of Australia(GNT1120249).
文摘Osteochondral defects are caused by injury to both the articular cartilage and subchondral bone within skeletal joints. They can lead to irreversible joint damage and increase the risk of progression to osteoarthritis. Current treatments for osteochondral injuries are not curative and only target symptoms, highlighting the need for a tissue engineering solution. Scaffold-based approaches can be used to assist osteochondral tissue regeneration, where biomaterials tailored to the properties of cartilage and bone are used to restore the defect and minimise the risk of further joint degeneration. This review captures original research studies published since 2015, on multiphasic scaffolds used to treat osteochondral defects in animal models. These studies used an extensive range of biomaterials for scaffold fabrication, consisting mainly of natural and synthetic polymers. Different methods were used to create multiphasic scaffold designs, including by integrating or fabricating multiple layers, creating gradients, or through the addition of factors such as minerals, growth factors, and cells. The studies used a variety of animals to model osteochondral defects, where rabbits were the most commonly chosen and the vast majority of studies reported small rather than large animal models. The few available clinical studies reporting cell-free scaffolds have shown promising early-stage results in osteochondral repair, but long-term follow-up is necessary to demonstrate consistency in defect restoration. Overall, preclinical studies of multiphasic scaffolds show favourable results in simultaneously regenerating cartilage and bone in animal models of osteochondral defects, suggesting that biomaterials-based tissue engineering strategies may be a promising solution.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.51303174,51273196,51203153,51233004,51390484,and 51321062)the Scientific Development Program of Jilin Province(Nos.20140520050JH and 20140309005GX)the Science and Technology Planning Project of Changchun City(No.14KG045).
文摘The osteochondral defects caused by vigorous trauma or physical disease are difficult to be managed.Tissue engineering provides a possible option to regenerate the damaged osteochondral tissues.For osteochondral reconstruction,one intact scaffold should be considered to support the regeneration of both cartilage and subchondral bone.Therefore,the biphasic scaffolds with the mimic structures of osteochondral tissues have been developed to close this chasm.A variety of biomimetic bilayer scaffolds fabricated from natural or synthetic polymers,or the ones loading with growth factors,cells,or both of them make great progresses in osteochondral defect repair.In this review,the preparation and in vitro and/or in vivo verification of bioinspired biphasic scaffolds are summarized and discussed,as well as the prospect is predicted.
基金supported by the National Key Research and Development Program of China(2016YFB0700804)National Natural Science Foundation of China(NO.T2121004,31830029).
文摘Autologous mosaicplasty is a common approach used to treat osteochondral defects in clinical practice.Gap integration between host and transplanted plugs requires bone tissue reservation and hyaline cartilage regeneration without uneven surface,graft necrosis and sclerosis.However,poor gap integration is a serious concern,which eventually leads to deterioration of joint function.To deal with such complications,this study has developed a strategy to effectively enhance integration of the gap region following mosaicplasty by applying injectable bioactive supramolecular nanofiber-enabled gelatin methacryloyl(GelMA)hydrogel(BSN-GelMA).A rabbit osteochondral defect model demonstrated that BSN-GelMA achieved seamless osteochondral healing in the gap region between plugs of osteochondral defects following mosaicplasty,as early as six weeks.Moreover,the International Cartilage Repair Society score,histology score,glycosaminoglycan content,subchondral bone volume,and collagen II expression were observed to be the highest in the gap region of BSN-GelMA treated group.This improved outcome was due to bio-interactive materials,which acted as tissue fillers to bridge the gap,prevent cartilage degeneration,and promote graft survival and migration of bone marrow mesenchymal stem cells by releasing bioactive supramolecular nanofibers from the GelMA hydrogel.This study provides a powerful and applicable approach to improve gap integration after autologous mosaicplasty.It is also a promising off-the-shelf bioactive material for cell-free in situ tissue regeneration.
基金This work was financially supported by the Versus Arthritis(No.21160)Rosetree Trust(No.A1184)+2 种基金European Commission via H2020 MSCA RISE BAMOS programme(No.734156)Innovative UK via Newton Fund(No.102872)and Ministry of Science and Technology of China via National Key R&D Program(No.2018YFE0207900).
文摘Osteoarthritis is a degenerative joint disease,typified by the loss in the quality of cartilage and bone at the interface of a synovial joint,resulting in pain,stiffness and reduced mobility.The current surgical treatment for advanced stages of the disease is joint replacement,where the non-surgical therapeutic options or less invasive surgical treatments are no longer effective.These are major surgical procedures which have a substantial impact on patients’quality of life and lifetime risk of requiring revision surgery.Treatments using regenerative methods such as tissue engineering methods have been established and are promising for the early treatment of cartilage degeneration in osteoarthritis joints.In this approach,3-dimensional scaffolds(with or without cells)are employed to provide support for tissue growth.However,none of the currently available tissue engineering and regenerative medicine products promotes satisfactory durable regeneration of large cartilage defects.Herein,we discuss the current regenerative treatment options for cartilage and osteochondral(cartilage and underlying subchondral bone)defects in the articulating joints.We further identify the main hurdles in osteochondral scaffold development for achieving satisfactory and durable regeneration of osteochondral tissues.The evolution of the osteochondral scaffolds–from monophasic to multiphasic constructs–is overviewed and the osteochondral scaffolds that have progressed to clinical trials are examined with respect to their clinical performances and their potential impact on the clinical practices.Development of an osteochondral scaffold which bridges the gap between small defect treatment and joint replacement is still a grand challenge.Such scaffold could be used for early treatment of cartilage and osteochondral defects at early stage of osteoarthritis and could either negate or delay the need for joint replacements.
