针对骨质疏松的RNAi功能化种植体的构建、功效及机制研究

项目名称： 针对骨质疏松的RNAi功能化种植体的构建、功效及机制研究

项目编号： No.81470785

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张玉梅

作者单位： 中国人民解放军第四军医大学

项目金额： 100万元

中文摘要： 骨质疏松条件下的种植体骨结合是亟待解决的临床问题，仅依靠微纳米形貌修饰很难获得良好的骨结合，必须联合其它的种植体活化策略。RNAi技术可促进骨质疏松条件下的骨形成，因此，RNAi功能化有望成为一种理想选择。本课题在仿生微纳米形貌制备并对其生物学功能进行系统研究的基础上，针对骨质疏松条件进一步优化微纳米形貌，筛选骨质疏松条件下可促进骨形成的RNAi，选用生物相容性好的壳聚糖载体和可以达到长效缓释的阴极电沉积方法，对转染复合物及电沉积相关参数进行优化，构建RNAi功能化种植体。在此基础上，对其载荷量及缓释功能进行系统研究，采用骨质疏松动物模型和相关细胞对其转染和促骨结合功效进行系统评价并筛选出最佳的试样。最后，深入研究RNAi功能化种植体缓释、细胞转染及成骨作用的机制，为制备技术的进一步优化提供理论指导。最终形成可在骨质疏松条件下获得理想骨结合的功能化种植体，也为其他生物材料的活化提供参考。

中文关键词： 表面改性；RNAi；壳聚糖；药物缓释；骨质疏松

英文摘要： Poor implant osseointegration under osteoporotic condition is an urgent problem in clinic. Modification by micro-nano topographies can hardly fulfil the requirement and accompany with other strategies is essential. Among them, using RNA interference technique to facilitate osteogenesis under osteoporotic condition is an ideal selection. The project was established on our previous study of biomimetic approach to fabricate micro-nano topographies and further validation was needed, followed by RNAi functionalization. The biocompatible chitosan was chosen as vector to formulate transfection complexes and the parameter was confirmed. Meanwhile, the cathodic electrodeposition method was chosen to fabricate the coating due to its neutralizaion mechanism that resulted in prolonged degradation manner. The loading amount and release profile were performed. The in vitro and in vivo effects were carried out with related cells and osteoporotic animals. Finally, the mechanisms of sustained release, transfection and osteogenic effect were performed to better guide the coating optimization. Ultimately, the project wants to find out a kind of implant that could retain ideal ossointegration for osteoporotic condition and provide a model for molecules immobilization on other biomaterials.

英文关键词： surface modification;RNAi;chitosan;sustained release;osteoporosis