Engineering an extracellular matrix-functionalized,load-bearing tendon substitute for effective repair of large-to-massive tendon defects  

作　　者：Shuting Huang Ying Rao Meng Zhou Anna M.Blocki Xiao Chen Chunyi Wen Dai Fei Elmer Ker Rocky S.Tuan Dan Michelle Wang 

机构地区：[1]School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China [2]Institute for Tissue Engineering and Regenerative Medicine,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China [3]Ministry of Education Key Laboratory for Regenerative Medicine,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China [4]Department of Orthopaedics and Traumatology,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong SAR,China [5]Center for Neuromusculoskeletal Restorative Medicine,Hong Kong Science Park,Hong Kong SAR,China [6]Dr.Li Dak Sum-Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [7]Department of Sports Medicine,Zhejiang University School of Medicine,Hangzhou,China [8]China Orthopedic Regenerative Medicine Group(CORMed),Hangzhou,China [9]Interdisciplinary Division of Biomedical Engineering,The Hong Kong Polytechnic University,Hong Kong SAR,China

出　　处：《Bioactive Materials》2024年第6期221-237,共17页生物活性材料（英文）

基　　金：funding support,including The Research Grants Council of Hong Kong SAR(GRF 14121121,DMW,GRF 14118620,DMW,ECS24201720,DFEK);National Natural Science Foundation of China/Research Grants Council Joint Research Scheme(N_CUHK409/23,DMW);The Innovation and Technology Commission of Hong Kong SAR Innovation Tier 3 Support(ITS/090/18,DFEK);Health@InnoHK CNRM(DMW,AB,DFEK,RST).

摘　　要：A significant clinical challenge in large-to-massive rotator cuff tendon injuries is the need for sustaining high mechanical demands despite limited tissue regeneration,which often results in clinical repair failure with high retear rates and long-term functional deficiencies.To address this,an innovative tendon substitute named“BioTenoForce”is engineered,which uses(i)tendon extracellular matrix(tECM)’s rich biocomplexity for tendon-specific regeneration and(ii)a mechanically robust,slow degradation polyurethane elastomer to mimic native tendon’s physical attributes for sustaining long-term shoulder movement.Comprehensive assessments revealed outstanding performance of BioTenoForce,characterized by robust core-shell interfacial bonding,human rotator cuff tendon-like mechanical properties,excellent suture retention,biocompatibility,and tendon differentiation of human adipose-derived stem cells.Importantly,BioTenoForce,when used as an interpositional tendon substitute,demonstrated successful integration with regenerative tissue,exhibiting remarkable efficacy in repairing large-to-massive tendon injuries in two animal models.Noteworthy outcomes include durable repair and sustained functionality with no observed breakage/rupture,accelerated recovery of rat gait performance,and>1 cm rabbit tendon regeneration with native tendon-like biomechanical attributes.The regenerated tissues showed tendon-like,wavy,aligned matrix structure,which starkly contrasts with the typical disorganized scar tissue observed after tendon injury,and was strongly correlated with tissue stiffness.Our simple yet versatile approach offers a dual-pronged,broadly applicable strategy that overcomes the limitations of poor regeneration and stringent biomechanical requirements,particularly essential for substantial defects in tendon and other load-bearing tissues.

关 键 词：Tendon regeneration Large-to-massive tendon defect Tendon tissue engineering Extracellular matrix Polyurethane 

分 类 号：R318[医药卫生—生物医学工程]