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通过干细胞的拓扑自诱导实现具有生物学和生物力学异质性的功能性半月板重建。

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

作者信息

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

机构信息

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.

School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 639798, Singapore.

出版信息

Bioact Mater. 2024 Mar 11;36:358-375. doi: 10.1016/j.bioactmat.2024.03.005. eCollection 2024 Jun.

Abstract

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 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.

摘要

半月板损伤是膝关节最常见的运动损伤之一,也是骨关节炎(OA)的关键致病因素。目前的半月板替代产品由于无法从生物学和生物力学角度重建天然半月板的梯度异质性,远远不能恢复半月板的生物功能。在此,受拓扑自诱导效应和天然半月板微观结构的启发,我们通过基于机械/生物相容性兼容的高M聚(ε-己内酯)(PCL)的双阶段温度控制3D打印系统,提出了一种具有独特梯度尺寸菱形孔微观结构的创新型组织工程半月板(TEM)(GSDP-TEM)。在生物学上,独特的梯度微观拓扑结构允许接种的间充质干细胞进行空间异质性分化,引发细胞外基质(ECM)从内向外的梯度转变。在生物力学上,GSDP-TEM呈现出与天然半月板相似的优异周向拉伸模量和载荷传递能力。植入兔膝关节后,GSDP-TEM诱导仿生异质新半月板再生,并有效减轻关节退变。本研究为功能性半月板重建提供了一种创新策略。拓扑自诱导细胞分化和生物力学特性也为人体其他复杂异质结构重建提供了一种简单有效的解决方案,具有很高的临床转化潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1ba/10944202/3359ced0602b/ga1.jpg

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