Functional meniscus reconstruction with biological and biomechanical heterogeneities through topological self-induction of stem cells  

作　　者：Mingze Du Kangze Liu Huinan Lai Jin Qian Liya Ai Jiying Zhang Jun Yin Dong Jiang 

机构地区：[1]Department of Sports Medicine,Peking University Third Hospital,Institute of Sports Medicine of Peking University,Beijing Key Laboratory of Sports Injuries,Engineering Research Center of Sports Trauma Treatment Technology and Devices,Ministry of Education,Beijing,China [2]The State Key Laboratory of Fluid Power Transmission and Control Systems,Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province,School of Mechanical Engineering,Zhejiang University,Zhejiang,310058,China [3]Department of Engineering Mechanics,Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province,Zhejiang University,Zhejiang,310058,China [4]School of Chemistry,Chemical Engineering and Biotechnology,Nanyang Technological University,639798,Singapore

出　　处：《Bioactive Materials》2024年第6期358-375,共18页生物活性材料（英文）

基　　金：supported by National Key R&D Program of China(No.2019YFB1706905);National Natural Science Foundation of China(82072428,52075482);Natural Science Foundation of Beijing,China(7212132).

摘　　要：Meniscus injury is one of the most common sports injuries within the knee joint,which is also a crucial pathogenic factor for osteoarthritis(OA).The current meniscus substitution products are far from able to restore meniscal biofunctions due to the inability to reconstruct the gradient heterogeneity of natural meniscus from biological and biomechanical perspectives.Here,inspired by the topology self-induced effect and native meniscus microstructure,we present an innovative tissue-engineered meniscus(TEM)with a unique gradient-sized diamond-pored microstructure(GSDP-TEM)through dual-stage temperature control 3D-printing system based on the mechanical/biocompatibility compatible high M_(w) poly(ε-caprolactone)(PCL).Biologically,the unique gradient microtopology allows the seeded mesenchymal stem cells with spatially heterogeneous differentiation,triggering gradient transition of the extracellular matrix(ECM)from the inside out.Biomechanically,GSDP-TEM presents excellent circumferential tensile modulus and load transmission ability similar to the natural meniscus.After implantation in rabbit knee,GSDP-TEM induces the regeneration of biomimetic heterogeneous neomeniscus and efficiently alleviates joint degeneration.This study provides an innovative strategy for functional meniscus reconstruction.Topological self-induced cell differentiation and biomechanical property also provides a simple and effective solution for other complex heterogeneous structure reconstructions in the human body and possesses high clinical translational potential.

关 键 词：Tissue-engineered meniscus Functional reconstruction Mesenchymal stem cells HETEROGENEITY Topology structure 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学] R318[医药卫生—基础医学]