氧化钽纳米管内植物涂层通过调控衰老相关BMSCs成骨-成脂分化命运促进骨整合的作用机制研究

老年骨质疏松（OP）患者假体松动是临床难题。假体对于疏松骨质的骨整合性能欠优以及衰老骨髓间充质干细胞（BMSCs）成骨-成脂分化功能紊乱是其主要原因。为此，我们前期通过激光3D打印结合阳极氧化技术制备了具有氧化钽纳米管（NT）涂层的多孔钽支架，发现氧化钽NT涂层能够提高大鼠BMSCs成骨分化，并抑制其成脂分化。我们还发现氧化钽NT涂层可上调BMSCs中YAP和TAZ表达，且提高了多孔钽支架在老年OP大鼠骨中的初始稳定性。由此我们提出假说：通过对3D打印多孔钽支架进行NT涂层改性，可提高其生物活性并调控BMSCs成骨-成脂分化偏移，促进老年OP骨整合。本项目拟通过体内外老年OP模型探究NT涂层的多孔钽支架对BMSCs成骨-成脂分化和骨缺损中的骨整合效果。此外，还将通过YAP/TAZ探究氧化钽涂层调控老年OP患者BMSCs分化命运的潜在机制，为防治老年OP患者假体松动提供新的思路和理论基础。

The prosthesis loosening in elderly patients with osteoporosis (OP) is a challenging clinical problem, of which the main reasons can be attributed to the unsatisfied osteointegration property of the prosthesis to osteoporotic bone and the disorder of osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs) in elderly OP patients. Therefore, we prepared porous tantalum (Ta) scaffolds with tantalum oxide nanotubes (Ta2O5-NT) coating by laser 3D printing combined with anodizing technology. It was found that NT coating can improve the osteogenic differentiation and inhibit the adipogenic differentiation of BMSCs from rats in-vitro. We also found that Ta2O5-NT coating can up-regulate the expression of YAP and TAZ in BMSCs, and improve the initial mechanical stability of porous Ta in elderly rats with OP. The YAP/TAZ molecules have been found playing critical roles in regulating the osteogenic-adipogenic differentiation of BMSCs in published resaerch. Therefore, we propose a hypothesis that by modifying 3D printed porous Ta scaffolds with NT coating, we can improve their biological activity, regulate the osteogenic-adipogenic differentiation fate of BMSCs of elderly patients with OP, and promote the osteointegration of prosthesis in the elderly OP patients. Through in vitro and in vivo OP model experiments, the effect of NT coated porous Ta scaffolds on osteogenic-adipogenic differentiation of BMSCs from elderly OP patients and osteointegration in the elderly patients with OP. In addition, we will explore the potential mechanism of Ta2O5-NT coating to regulate the fate of BMSCs differentiation in elderly OP patients focusing on YAP/TAZ, so as to provide new ideas and theoretical basis for the prevention and treatment of prosthesis loosening in elderly OP patients.