针对骨质疏松条件的miRNAs缓释钛种植体制备和骨结合能力与分子机制研究

项目名称： 针对骨质疏松条件的miRNAs缓释钛种植体制备和骨结合能力与分子机制研究

项目编号： No.31500776

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 吴凯敏

作者单位： 中国人民解放军海军第九七一医院

项目金额： 21万元

中文摘要： 如何在骨质疏松（OP）这一骨代谢失衡条件下形成理想骨结合是牙科钛种植体亟待解决的问题。最近我们发现微弧氧化处理钛表面具有优秀的载药能力，同时考虑到antimiR-138与miR-34a可分别通过促成骨和抑破骨正向调节骨代谢平衡，本课题提出联合采用共价结合和自组装多层复合技术，在微弧氧化处理钛表面构建稳固结合且可同时缓释壳聚糖/antimiR-138和壳聚糖/miR-34a的涂层以在OP患者体内获得长效骨结合能力。对涂层中miRNA活性和释放进行系统表征，体外观察该涂层对间充质干细胞和破骨前体细胞功能特别是成骨和破骨分化的影响，体内观察在OP动物模型内的骨结合情况，筛选出最佳的涂层构成。深入探索持续作用的促成骨和抑破骨双因素共同对骨代谢相关信号通路的作用以指导优化种植体构建。该新型涂层有望在OP患者体内获得更好的种植体骨结合，同时为其它生物材料的设计提供借鉴。

中文关键词： 骨质疏松；miRNAs；钛种植体；骨结合；信号通路

英文摘要： How to create the ideal osseointegration under the condition of osteoporosis with disordered balance of bone metabolism turns into an urgent problem for the tianium implants. Recently, we have reported that MAO Ti surfaces can actually serve as a good drug loading and delivering platform. Considering the outstanding ability of antimiR-138 and miR-34a which work respectively through promoting osteogenesis and suppressing osteoclastogenesis to positively regulate bone turnover, we plan to develop chitosan/antimiR-138 and chitosan/miR-34a loading MAO coating on dental implant by covalently binding and layer-by-layer self-assembly. The novel coating is hoped to be firmly combined and long-lastingly release antimiR-138 and miR-34a in a controlled mode, finally leading to faster and better osseointegration in osteoporotic condition. After fabrication, the surface properties of the miRNAs loading MAO Ti surfaces will be well characterized, including stability and release rate. In vitro experiments will be conducted to observe the effect of the miRNAs loading MAO Ti surfaces on bone mesenchymal stem cell and osteoclast precursor cells functions, especially osteogenic differentiation and osteoclast differentiation. Then the in vivo osseointegration of the miRNAs loading MAO Ti surfaces will be observed in osteoporotic rats to determine the sample that generates the best osseointegration in the osteoporotic condition. Further, the influence of the long-lasting effect of the two factors of promoting osteogenesis and suppressing osteoclastogenesis on bone turnover related signal pathways will be inspected to deeply understanding their biological effect and further guide the structure optimization of the miRNAs loading MAO Ti surfaces. The miRNAs loading MAO Ti surfaces, combining the dual effects of antimiR-138 and miR-34a, are very promising to generate good in vivo osseointegration in the osteoporotic condition. The technique reported here can be also extended to other biomaterials.

英文关键词： Osteoporosis;miRNAs;Titanium implant;Osseointegration;Signal pathway