关节软骨弥漫性表浅缺损是骨关节炎的常见病理特征，但软骨表浅缺损面的细胞移植和材料粘附困难导致其修复依旧是临床上的巨大挑战。本项目模拟墙纸黏附翻修墙壁的策略，设计一种组织表面粘附力强，细胞相容性好、具有仿生微环境且便于操作的“分子胶水”，复合高细胞密度且可仿生软骨表层ECM膜状结构的MSCs细胞片，用于关节软骨的表浅型缺损修复研究。首先；以可原位成胶且提供促进组织粘附的分子锚定位点的邻硝基苄基苯光扳机接枝的硫酸软骨素及透明质酸为胶水基体材料，探索材料配比与组织粘附性能的关系；其次，获取MSCs细胞片，研究“分子胶水”微环境对MSCs细胞片的体外功能调控；最后，将成软骨诱导的MSCs细胞片复合仿生“分子胶水”移植到软骨缺损部位，分析细胞片及胶水材料与周围组织的整合，并评价其体内修复效果。本项目将为关节软骨表浅型缺损的修复及再生研究提供新的思路及理论指导。

Partial-thickness cartilage defect is a common pathological feature of osteoarthritis (OA), but difficulties of cell transplantation and material integration on the surface of partial-thickness cartilage defect make it a great clinical challenge to repair. In this project, inspired by the renovation strategy of wallpaper, we aim to design a novel kind of “molecular glue” with strong tissue adhesion, good biocompatibility, biomimetic microenvironment and easy operation properties, combined with MSCs cell sheets which show high cell densities and biomimetic membrane structure of cartilage surface, to synergistically repair partial-thickness cartilage defect of OA. First, N-(2-aminoethyl)-4-(4 (hydroxymethyl)-2-methoxy-5-nitrosophenoxy) butanamide modified chondroitin sulfate and hyaluronic acid will be used as glue matrix materials, which can be UV-crosslinked in situ and provide molecular anchor sites to promote tissue adhesion. The relationship between material ratio and tissue adhesion will be further explored. Second, the MSCs cell sheets will be noninvasively obtained, and the regulated effects of “molecular glue” microenvironment on the cell sheets function in vitro will be studied. Last, chondrogenesis induced MSCs cell sheets and the “molecular glue” will be transplanted to the cartilage defect, and the integration of cell sheets and glue with the surrounding tissues and their repair effects in vivo will be evaluated. This project will provide new idea and theoretical direction for the repair and regeneration of partial-thickness cartilage defects.