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

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.

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。

钛材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医学领域。不足之处是钛基植入体因与周边骨组织间缺乏整合性，以致长期植入稳定性差，是其临床应用面临的普遍挑战。本项目利用阳极氧化法在钛材表面构建一系列不同管径钛纳米管，为深入探究其作用机理，做了进一步修饰研究：1）利用直接滴加法将药物辛伐他汀/褪黑素装载入纳米管，并利用层层自组装技术在表面组装多层膜，成功构建了药物缓释系统，有效控制了药物的释放，促进了细胞成骨分化；2）利用生物化学连接法将生物相容性良好的成骨生长肽/明胶等修饰在纳米管表面，构建了良好的细胞微环境，从而有效提高了成骨作用。除此之外，初步探究了纳米管纳米结构的作用机理。本研究将为钛基植入体的表面结构与生物功能化修饰提供理论参考，并为研发新型医用钛基植入体材料提供科学依据。