内皮祖细胞适配子修饰StarPEG/去细胞瓣叶支架调控心脏瓣膜再生的机制

There are two key problems need to be resolved for the ideal heart valve prosthesis construction. First, accelerating the endothelialization of scaffold. Second, impove the mechanical property of scaffold. Aptamer that can specific binding the EPCs is prepared using SELEX technique. Then, StarPEG/decellularized porcine heart valve leaflets scaffold is modified by the aptamer to construct novel hybrid scaffold. The mechanism of the EPCs in the blood recruited and adhered to the novel hybrid scaffold, the endothelialization of scaffold accelerating, and thrombogenesis, immune and inflammatory reaction prevented is investigated. In the same time, the mechanical property and durability of novel hybrid scaffold is improved. And during the process of heart valve regeneration in vivo, the mechanism of the effects of EPCs recruited, adhered, endothelialization and mechanical property is explored.

目前理想心脏瓣膜替代物研究领域的热点和难点是组织工程支架材料植入体内后出现：（1）内皮化不足，导致血栓形成，免疫和炎症反应；（2）力学性能不足。本课题组在前期研究基础上，采用指数扩增配体的系统进化技术，制备能特异性结合内皮祖细胞(EPCs)的适配子(aptamer)，通过aptamer分子-NH2与星形聚乙二醇（StarPEG）分子-NCO的共价键合反应，对StarPEG /去细胞猪瓣叶支架进行修饰改性，构建新型复合支架，并阐明在体内环境下，新型复合支架对循环血EPCs的特异性招募、黏附、促进支架内皮化，防止血栓形成、免疫和炎症反应的机制。同时利用新型复合支架良好的力学性能，增强体内环境下的耐久性，防止衰败。在此基础上探讨EPCs招募、黏附－支架内皮化－力学性能－心脏瓣膜再生之间的内在调控机制。

促进支架内皮化和改善力学性能是实现体内心脏瓣膜再生需要解决的两大关键问题。本课题组采用指数扩增配体的系统进化技术，制备特异性结合内皮祖细胞(EPCs)的适配子(aptamer)，通过aptamer分子-NH2与聚乙二醇（PEG）分子-NCO的共价键合反应，对PEG/去细胞瓣叶支架进行修饰改性，构建新型复合支架。新型复合支架体内外试验结果显示支架表面有EPCs黏附，构建的组织工程心脏瓣膜（TEHV）在生物学和力学性能上与天然瓣膜相似。本项目探讨了EPCs招募、黏附—支架内皮化－力学性能－心脏瓣膜再生之间的内在调控机制，并为新型瓣膜替代物的研发提供了新思路。