项目名称： 钛材纳米界面原位调控骨髓间充质干细胞分化的分子机制研究

项目编号： No.31500766

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： 来敏

作者单位： 江苏师范大学

项目金额： 20万元

中文摘要： 钛及钛合金由于具有良好的物理性能已被作为植入体材料广泛应用于骨科临床领域。不足之处是，钛基植入体因与周边骨组织间缺乏整合性，以致其长期植入稳定性差，是其临床应用面临的普遍挑战。表面纳米结构能够很好地模拟人体骨组织微环境，且可能具有良好的成骨生物学效应，但细胞对纳米结构所产生的直接机械力学刺激的识别机制、信号转导机制和响应机制等尚不清楚。鉴于此，本项目在我们前期构建系列钛纳米管并研究其生物学效应的基础上，拟从力传导角度探讨钛纳米管调控骨髓间充质干细胞定向成骨分化的分子机制，包括机械传递子（如粘着斑激酶、RhoA/Rho相关蛋白激酶和肌球蛋白Ⅱ）是否参与纳米界面原位调控细胞定向成骨分化以及不同信号通路间的相互作用与相互关系，以期深入认识钛基纳米界面原位调控干细胞成骨分化的机理。本研究将为钛基植入体的表面结构优化设计以及后续蛋白/基因修饰提供理论参考，并为研发新型医用钛基植入体材料提供科学依据。

中文关键词： 钛材；表面纳米结构；骨髓间充质干细胞；分化；骨整合性

英文摘要： Titanium (Ti) and its alloys have been widely applied as bone implants in clinical applications because of their good mechanical properties. Nevertheless，titanium based materials are lack of osseointegration between the implant and its surrounding nature bone tissue, which results in poor long-term stability of the implant. It is the common challenge in clinical application. Surface nanostructure may exhibit good biological effects on osteogenesis mimicking the microenvironment of the human bone tissue. However, the mechanisms of recognition, signal pathway and response activated by direct mechanical stimulation from surface nanostructure are poorly understood. Considering these issues, On the basis of our previous studies that have shown a series of TiO2 nanotubes with different diameters were fabricated having good biocompatibility, In the point of mechanotransduction, this project explores and interprets the molecular mechanisms for the differentiation of mesenchymal stem cells regulated by TiO2 nanotubes, including whether mechanical transfers (such as focal adhesion kinase (FAK), RhoA/ROCK and myosinⅡ) being involved in interface regulated in situ differentiation of mesenchymal stem cells and cross-talking of different signal transduction pathways. This study provides theoretical references for the structure optimization design and subsequent protein/genetic modification of titanium-based implants. At the same time, it provides scientific basis for the fabrication of high-performance titanium-based implants with enhanced bone osseointegration.

英文关键词： titanium based materials;surface nanostructure;mesenchymal stem cell;differentiation;osseointegration