多孔支架表面微纳分级结构协同化学刺激对骨修复的影响及机制研究

在骨修复进程中，骨组织工程支架表面微纳米拓扑结构与化学刺激在调控细胞行为、提高成骨活性方面发挥了关键作用。然而，如何对支架进行合理设计，使其既适合细胞增殖和成骨分化，又能诱导新生血管生成，目前仍面临重大挑战。基于前期研究基础，本研究拟利用三维打印技术和仿生合成手段来解决这一问题。具体内容为：通过三维打印技术获得高强度β-磷酸三钙多孔支架，在柠檬酸钠调控下，引入微量元素Sr和Co，从而对支架表面羟基磷灰石（HAp）微纳米颗粒结构和化学组成进行精确控制，最终获得具备多种分级结构、微量元素释放可控的HAp三维支架体系。通过分别考察细胞在单一刺激（微纳分级结构或化学刺激）以及双重刺激作用下的粘附、迁移、增殖等行为，在细胞和分子水平上检测细胞成骨及成血管相关标记基因和蛋白的表达，探索微纳分级结构和化学刺激两种作用方式对细胞调控的分子机制和协同调控规律，为新型骨修复材料的开发提供可靠的理论依据。

In the process of bone repairing, micro/nano topological structure and chemical stimulation play important role in modifying cell behavior and promoting osteogenic activity. However, it’s still a big challenge to construct a proper scaffold, which not only promotes the proliferation, osteogenesis differentiation of the mesenchymal stem cells (MSCs), but also stimulates angiogenesis process. Based on our previous research results, 3D printing technology and biomimetic synthesis method will be used in this study. The research contents mainly include: high mechanical strength porous scaffold of β-tricalcium phosphate will be prepared by 3D printing; the microstructure and the chemical composition of the 3D scaffold is adjusted by adding Sr and Co with the aid of sodium citrate. Finally, a 3D scaffold with stable hierarchical structure and controllable releasing of trace elements will be obtained. Moreover, the cellular behaviors (such as adhesion, migration and proliferation etc), and gene expression related to the osteogenesis differentiation and angiogenesi, will be systematic studied in the presence of single stimulation (topological structure or chemical stimulation) and synergistic stimulating, respectively. We expect that some novel understanding and knowledge for osteogenic differentiation and angiogenesis can be obtained. That will further provide important theoretical basis for developing novel bone tissue repair materials.