TiO2纳米管负载淫羊藿苷对骨质疏松下钛种植体骨结合的作用及分子机理研究

项目名称： TiO2纳米管负载淫羊藿苷对骨质疏松下钛种植体骨结合的作用及分子机理研究

项目编号： No.31470920

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 李长义

作者单位： 天津医科大学

项目金额： 75万元

中文摘要： 骨质疏松易造成种植体初期稳定性降低和延迟骨结合，影响种植成功率，是种植临床工作难点。淫羊藿苷具有骨诱导性，可促进成骨、血管生成，抑制骨质吸收，治疗骨质疏松效果明确，无毒副作用。本研究拟通过阳极氧化方法在纯钛表面制备TiO2纳米管，在此基础上负载淫羊藿苷。通过试件表征和药物释放实验研究纳米管内淫羊藿苷加载及释放规律；采用骨髓间充质干细胞体外培养实验探讨纳米管和淫羊藿苷单独作用与协同作用下对骨髓间充质干细胞增殖、分化和信号通路及分子网络的影响；经由骨质疏松兔模型研究纳米管和淫羊藿苷单独与协同作用下诱导骨-种植体界面骨结合的分子机制。进一步采用基因芯片和生物信息学手段，全面快速分析TiO2纳米管负载淫羊藿苷对种植体表面成骨、破骨相关基因表达的影响，筛选并验证关键性的成骨信号通路，探讨TiO2纳米管负载淫羊藿苷的分子作用机制，为骨质疏松条件下种植体表面改性提供新思路和理论基础。

中文关键词： TiO2纳米管；钛种植体；骨质疏松；淫羊藿苷；分子机制

英文摘要： Patients with osteoporosis is prone to suffering from decreased primary stability and delay bone bonding during implant treatment.This may impair the successful rate in implant surgery. To increase implant's early stability so as to achieve early osseointegration is one of the key problems in dental implantology. Icariin has the osteoinductivity, could promote osteogenisis, angiogenesis and inhibit bone absorption, and is effective on curing osteoporosis, without adverse effect. In the present research, we combined the modern TiO2 nanotube preparation technology and traditional Chinese herb icariin to establish the new implant surface which could promote the implant osseointegration. We constructed the TiO2 nanotube by anodic oxidation, then loaded icariin onto nanotube. This subject studies the release rules of the icariin loaded TiO2 nanotube surface of titanium implant through surface characterization and drug delivery test. We further cocultured the icariin loaded TiO2 nanotube titanium implant material with bone marrow mesenchymal stem cells to examine its bioactivity in vitro and further implanted into rabbit tibia to examine its bone bonding ability in vivo. The proliferation, differentiation effect, molecular signaling pathway and network change in icariin loaded TiO2 nanotube titanium implant material are examined. In addtion, the high throughput Gene Chip technology was combined with bioinformatics method, to screen the osteogenesis-related and osteoclast-related gene expression, signal pathway and molecular network. In the present study, we explore the underlying molecular mechanism of TiO2 tube and icariin to promote the osteogenic activity respectively and their synergistic action in vitro and osseointegration in vivo. The results will provide theoretic basis for improve the osseointegration of titanium implant under osteoporosis situation.

英文关键词： TiO2 nanotube;titanium implant;osteoporosis;icariin;molecular mechanism