负载KGN及SMSCs脂质体锚定的混合微凝胶通过CCN1/CYR61调控促进软骨修复的机制研究

关节软骨损伤十分常见，但目前仍缺乏完好、快速及稳定的软骨修复手段。本课题组前期运用骨髓间充质干细胞BMSCs复合聚乙烯醇/壳聚糖（PVA/CS）多孔水凝胶在动物体内实现了软骨缺损的修复，但发现其无法实现微创植入，且与正常软骨整合不佳。基于此，项目组制备了光控自愈负载KGN及滑膜来源间充质干细胞（SMSCs）脂质体锚定的混合微凝胶，实现了微凝胶与组织之间的快速整合。同时发现其可有效促进SMSCs向软骨分化，且伴随半胱氨酸富集的蛋白61(CCN1/CYR61)表达显著上升。结合文献及前期研究成果，本研究拟：1）通过微流控技术或乳液法制备脂质体锚定的包裹KGN及SMSCs的可注射PVA/CS微凝胶，观察其表征及缓释性能；2）进一步应用体外及体内实验评价材料对软骨损伤修复效果，并探讨KGN通过CCN1/CYR61发挥调控作用机制。以期为软骨损伤的新型治疗手段提供理论依据。

Articular cartilage damage is very common, but there is still a lack of intact, rapid and stable cartilage repair methods. The research group used bone marrow mesenchymal stem cell BMSCs composited with polyvinyl alcohol/chitosan (PVA/CS) porous hydrogel to repair cartilage defects in animals previously, but found that it was unable to achieve minimally invasive implantation, and it was incompatible with poor integration of normal cartilage. Based on this, the project team prepared a light-controlled self-healing hybrid microgel anchored by liposomes contained KGN and synovial-derived mesenchymal stem cells (SMSCs) , realizing the rapid integration between the microgel and the tissue. At the same time, it was found that it can effectively promote the differentiation of SMSCs into cartilage cells, and the expression of protein 61 (CCN1/CYR61) with cysteine ​​enrichment increased significantly.Combining literature and previous research results, this study intends to: 1) prepare liposome-anchored injectable PVA/CS microgels encapsulating KGN and SMSCs by microfluidic technology or emulsion method, and observe its characterization and sustained-release properties; 2) Furtherly use in vitro and in vivo experiments to evaluate the effect of materials on cartilage damage repair, and to explore the mechanism of KGN through CCN1/CYR61 with the aim to provide a theoretical basis for a new type of treatment of cartilage injury.