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
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
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
背景:由于关节软骨的解剖、生理特点,其自我修复能力有限,故而如何修复大面积的软骨缺损(直径>4 mm)成为医学界备受瞩目的问题之一。伴随生物材料和组织工程学科的发展,通过支架技术尤其具有模拟细胞外基质微环境的水凝胶支架研究的...背景:由于关节软骨的解剖、生理特点,其自我修复能力有限,故而如何修复大面积的软骨缺损(直径>4 mm)成为医学界备受瞩目的问题之一。伴随生物材料和组织工程学科的发展,通过支架技术尤其具有模拟细胞外基质微环境的水凝胶支架研究的深入发展,为软骨损伤修复提供了新的治疗思路。目的:就海藻酸盐的性质、海藻酸盐水凝胶支架的制备以及在软骨损伤修复中的研究进展进行综述。方法:利用计算机检索Web of Science、PubMed、万方和中国知网数据库,中文检索词为“海藻酸盐水凝胶、软骨组织工程或软骨、骨软骨、支架”,英文检索词为“alginate hydrogel,cartilage tissue engineering or chondro*,osteochondral,scaffold”,检索文献时间范围2016年1月至2020年12月。最终按入组标准筛选后纳入60篇文献进行综述分析。结果与结论:①海藻酸盐作为带负电荷的天然亲水性多糖,可通过修饰技术赋予传统海藻酸盐水凝胶更优良的机械性能、黏附性、生物降解性以及生物相容性等。②修饰后的海藻酸盐复合水凝胶支架利于维持种子细胞的正常形态、合成相应的细胞外基质,促进成软骨相关基因的表达,表现出优良的成软骨能力。③有报道证实海藻酸盐复合水凝胶支架可在动物体内形成与周边正常软骨相似的软骨组织,有效修复缺损部位。④因此,海藻酸盐复合水凝胶支架具备良好的促软骨修复能力,为软骨组织工程提供新的治疗思路,但该材料未来还需更完善的临床前试验数据的支撑,以推进其临床转化进程。展开更多
AIM To clarify the effectiveness of scaffold-based therapy for osteochondral lesions of the talus(OLT). METHODS A systematic search of MEDLINE and EMBASE databases was performed during August 2016 and updated in Janua...AIM To clarify the effectiveness of scaffold-based therapy for osteochondral lesions of the talus(OLT). METHODS A systematic search of MEDLINE and EMBASE databases was performed during August 2016 and updated in January 2017. Included studies were evaluated with regard to the level of evidence(LOE) and quality of evidence(QOE) using the Modified Coleman Methodology Score. Variable reporting outcome data, clinical outcomes, and the percentage of patients who returned to sport at previous level were also evaluated. RESULTS Twenty-eight studies for a total of 897 ankles were included; 96% were either LOE Ⅲ or Ⅳ. Studies were designated as either of poor or fair quality. There were 30 treatment groups reporting six different scaffold repair techniques: 13 matrix-induced autologous chondrocyte transplantation(MACT), nine bone marrow derived cell transplantation(BMDCT), four autologous matrixinduced chondrogeneis(AMIC), and four studies of other techniques. The categories of general demographics(93%) and patient-reported outcome data(85%) were well reported. Study design(73%), imaging data(73%), clinical variables(49%), and patient history(30%) were also included. The weighted mean American Orthopaedic Foot and Ankle Society(AOFAS) score at final follow-up was: 86.7 in MACT, 88.2 in BMDCT, and 82.3 in AMIC. Eight studies reported that a weighted mean of 68.3% ofpatients returned to a previous level of sport activity. CONCLUSION Scaffold-based therapy for OLT may produce favorable clinical outcomes, but low LOE, poor QOE, and variability of the data have confounded the effectiveness of this treatment.展开更多
The repair of osteochondral defects is one of the major clinical challenges in orthopaedics.Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defec...The repair of osteochondral defects is one of the major clinical challenges in orthopaedics.Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects.However,less success has been achieved for the regeneration of large defects,which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue.In this study,we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques.The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite system.The microstructure and mechanical properties of the scaffold were examined,and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model.The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold,and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage,as demonstrated by hyaline-like cartilage formation.The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group.Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group.The findings showed the safety and efficacy of the cell-free“translation-ready”osteochondral scaffold,which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.展开更多
In the field of tissue engineering,there is significant subsidence of the porous design scaffold several months after implantation.To avoid stress shielding and stimulate bone and cartilage ingrowth,high scaffold poro...In the field of tissue engineering,there is significant subsidence of the porous design scaffold several months after implantation.To avoid stress shielding and stimulate bone and cartilage ingrowth,high scaffold porosity is needed to diminish the mechanical properties of the scaffold.The closer the mechanical properties of the scaffold are to those of surrounding tissues,the better biological properties it will get.Besides,adequate mechanical stability is needed as the scaffold needs to be well fixed in the target area and it will endure load after surgery.Evaluating the mechanical fixation of the scaffold at the initial stage and the long-term performance of a scaffold for in vivo study is hard,as no facility can be put into the target area for the friction test.This study investigated the mechanical stability of the biomimetic scaffold at the initial stage of implantation by finite element analysis(FEA).According to in vivo study,scaffold could not maintain its original position and would sink 1-2 mm in the target area.The simulation results suggested that mechanical loading is not the main reason for scaffold subsidence.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
按一定比例混合Ⅱ型胶原、丝素蛋白与透明质酸3种天然材料,运用冷冻干燥技术与天然软骨下骨交联,制备出同时具有软骨层和软骨下骨层的骨软骨一体化支架。采用扫描电子显微镜(scanning electron microscope,SEM)及非接触数字技术研究分...按一定比例混合Ⅱ型胶原、丝素蛋白与透明质酸3种天然材料,运用冷冻干燥技术与天然软骨下骨交联,制备出同时具有软骨层和软骨下骨层的骨软骨一体化支架。采用扫描电子显微镜(scanning electron microscope,SEM)及非接触数字技术研究分析支架的表观与微观结构,通过压缩试验及循环载荷下的平均应变试验,对支架的力学性能进行检测。结果表明:制备出的骨软骨一体化支架软骨层呈多孔孔隙结构,通透性较好,且具有明显的率相关性;随着压缩速率的增加,支架的弹性模量增加;在循环压缩载荷作用下,支架显示了应力-应变滞环曲线,随着加载圈数的增加,支架表现出明显的平均应变行为,对骨软骨缺损修复具有重要的临床价值。展开更多
Currently,osteochondral(OC)tissue engineering has become a potential treatment strategy in repairing chondral lesions and early osteoarthritis due to the limited self-healing ability of cartilage.However,it is still c...Currently,osteochondral(OC)tissue engineering has become a potential treatment strategy in repairing chondral lesions and early osteoarthritis due to the limited self-healing ability of cartilage.However,it is still challenging to ensure the integrity,physiological function and regeneration ability of stratified OC scaffolds in clinical application.Biomimetic OC scaffolds are attractive to overcome the above problems because of their similar biological and mechanical properties with native OC tissue.As a consequence,the researches on biomimetic design to achieve the tissue function of each layer,and additive manufacture(AM)to accomplish composition switch and ultrastructure of personalized OC scaffolds have made a remarkable progress.In this review,the design methods of biomaterial and structure as well as computer-aided design,and performance prediction of biopolymer-based OC scaffolds are presented;then,the characteristics and limitations of AM technologies and the integrated manufacture schemes in OC tissue engineering are summarized;finally,the novel biomaterials and techniques and the inevitable trends of multifunctional bio-manufacturing system are discussed for further optimizing production of tissue engineering OC scaffolds.展开更多
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.
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.
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.
文摘背景:由于关节软骨的解剖、生理特点,其自我修复能力有限,故而如何修复大面积的软骨缺损(直径>4 mm)成为医学界备受瞩目的问题之一。伴随生物材料和组织工程学科的发展,通过支架技术尤其具有模拟细胞外基质微环境的水凝胶支架研究的深入发展,为软骨损伤修复提供了新的治疗思路。目的:就海藻酸盐的性质、海藻酸盐水凝胶支架的制备以及在软骨损伤修复中的研究进展进行综述。方法:利用计算机检索Web of Science、PubMed、万方和中国知网数据库,中文检索词为“海藻酸盐水凝胶、软骨组织工程或软骨、骨软骨、支架”,英文检索词为“alginate hydrogel,cartilage tissue engineering or chondro*,osteochondral,scaffold”,检索文献时间范围2016年1月至2020年12月。最终按入组标准筛选后纳入60篇文献进行综述分析。结果与结论:①海藻酸盐作为带负电荷的天然亲水性多糖,可通过修饰技术赋予传统海藻酸盐水凝胶更优良的机械性能、黏附性、生物降解性以及生物相容性等。②修饰后的海藻酸盐复合水凝胶支架利于维持种子细胞的正常形态、合成相应的细胞外基质,促进成软骨相关基因的表达,表现出优良的成软骨能力。③有报道证实海藻酸盐复合水凝胶支架可在动物体内形成与周边正常软骨相似的软骨组织,有效修复缺损部位。④因此,海藻酸盐复合水凝胶支架具备良好的促软骨修复能力,为软骨组织工程提供新的治疗思路,但该材料未来还需更完善的临床前试验数据的支撑,以推进其临床转化进程。
文摘AIM To clarify the effectiveness of scaffold-based therapy for osteochondral lesions of the talus(OLT). METHODS A systematic search of MEDLINE and EMBASE databases was performed during August 2016 and updated in January 2017. Included studies were evaluated with regard to the level of evidence(LOE) and quality of evidence(QOE) using the Modified Coleman Methodology Score. Variable reporting outcome data, clinical outcomes, and the percentage of patients who returned to sport at previous level were also evaluated. RESULTS Twenty-eight studies for a total of 897 ankles were included; 96% were either LOE Ⅲ or Ⅳ. Studies were designated as either of poor or fair quality. There were 30 treatment groups reporting six different scaffold repair techniques: 13 matrix-induced autologous chondrocyte transplantation(MACT), nine bone marrow derived cell transplantation(BMDCT), four autologous matrixinduced chondrogeneis(AMIC), and four studies of other techniques. The categories of general demographics(93%) and patient-reported outcome data(85%) were well reported. Study design(73%), imaging data(73%), clinical variables(49%), and patient history(30%) were also included. The weighted mean American Orthopaedic Foot and Ankle Society(AOFAS) score at final follow-up was: 86.7 in MACT, 88.2 in BMDCT, and 82.3 in AMIC. Eight studies reported that a weighted mean of 68.3% ofpatients returned to a previous level of sport activity. CONCLUSION Scaffold-based therapy for OLT may produce favorable clinical outcomes, but low LOE, poor QOE, and variability of the data have confounded the effectiveness of this treatment.
基金financially supported by the Versus Arthritis (No. 21160)the Rosetree Trust (No. A1184)+2 种基金the European Commission via H2020-MSCA-RISE Program (BAMOS Project (No.734156))Innovate UK via Newton Fund (No. 102872)the Engineering and Physical Science Research Council (EPSRC) via DTP Case Programme (No. EP/T517793/1)
文摘The repair of osteochondral defects is one of the major clinical challenges in orthopaedics.Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects.However,less success has been achieved for the regeneration of large defects,which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue.In this study,we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques.The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite system.The microstructure and mechanical properties of the scaffold were examined,and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model.The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold,and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage,as demonstrated by hyaline-like cartilage formation.The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group.Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group.The findings showed the safety and efficacy of the cell-free“translation-ready”osteochondral scaffold,which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.
基金financially supported by Versus Arthritis Research UK (No.21977)European Commission via a H2020-MSCA-RISE Programme (BAMOS,No.734156)+2 种基金Innovative UK via Newton Fund (No.102872)Engineering and Physical Science Research Council (EPSRC) via DTP CASE Programme (No.EP/T517793/1)the Intergovernmental Cooperation in Science and Technology of China (No.2016YFE0125300)
文摘In the field of tissue engineering,there is significant subsidence of the porous design scaffold several months after implantation.To avoid stress shielding and stimulate bone and cartilage ingrowth,high scaffold porosity is needed to diminish the mechanical properties of the scaffold.The closer the mechanical properties of the scaffold are to those of surrounding tissues,the better biological properties it will get.Besides,adequate mechanical stability is needed as the scaffold needs to be well fixed in the target area and it will endure load after surgery.Evaluating the mechanical fixation of the scaffold at the initial stage and the long-term performance of a scaffold for in vivo study is hard,as no facility can be put into the target area for the friction test.This study investigated the mechanical stability of the biomimetic scaffold at the initial stage of implantation by finite element analysis(FEA).According to in vivo study,scaffold could not maintain its original position and would sink 1-2 mm in the target area.The simulation results suggested that mechanical loading is not the main reason for scaffold subsidence.
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.
文摘按一定比例混合Ⅱ型胶原、丝素蛋白与透明质酸3种天然材料,运用冷冻干燥技术与天然软骨下骨交联,制备出同时具有软骨层和软骨下骨层的骨软骨一体化支架。采用扫描电子显微镜(scanning electron microscope,SEM)及非接触数字技术研究分析支架的表观与微观结构,通过压缩试验及循环载荷下的平均应变试验,对支架的力学性能进行检测。结果表明:制备出的骨软骨一体化支架软骨层呈多孔孔隙结构,通透性较好,且具有明显的率相关性;随着压缩速率的增加,支架的弹性模量增加;在循环压缩载荷作用下,支架显示了应力-应变滞环曲线,随着加载圈数的增加,支架表现出明显的平均应变行为,对骨软骨缺损修复具有重要的临床价值。
基金Funding was supported by the Key Research and Development Program of Shaanxi Province(Grant No.2020ZDLSF04-07)the National Key Research and Development Program of China(Grant No.2019QY(Y)0502)+2 种基金the National Natural Science Foundation of China(Grant No.51905438)the Innovation Platform of Biofabrication(Grant No.17SF0002)the Fundamental Research Funds for the Central Universities(Grant No.31020190502009).
文摘Currently,osteochondral(OC)tissue engineering has become a potential treatment strategy in repairing chondral lesions and early osteoarthritis due to the limited self-healing ability of cartilage.However,it is still challenging to ensure the integrity,physiological function and regeneration ability of stratified OC scaffolds in clinical application.Biomimetic OC scaffolds are attractive to overcome the above problems because of their similar biological and mechanical properties with native OC tissue.As a consequence,the researches on biomimetic design to achieve the tissue function of each layer,and additive manufacture(AM)to accomplish composition switch and ultrastructure of personalized OC scaffolds have made a remarkable progress.In this review,the design methods of biomaterial and structure as well as computer-aided design,and performance prediction of biopolymer-based OC scaffolds are presented;then,the characteristics and limitations of AM technologies and the integrated manufacture schemes in OC tissue engineering are summarized;finally,the novel biomaterials and techniques and the inevitable trends of multifunctional bio-manufacturing system are discussed for further optimizing production of tissue engineering OC scaffolds.