骨质疏松微环境响应性钛植入体复合界面的构建与骨折重建效应的研究

Characteristic features of osteoporosis include low bone density and high fragility. The fracture site can't integrate with the internal fixation implant rapidly and stably, which usually results in the failure of bone fracture repair. In this project, we would like to fabricate a composite titanium implant based on the characteristic features of the osteoporotic bone microenvironment (local acidity and high concentration of cathepsin K) and the mesenchymal stem cells under osteoporotic conditions (low cell-recruiting efficiency and osteogenicity), which could release SDF-1α, anti-osteoporosis drugs like alendronate and bone-inductive biomolecules such as 17β-estradiol in response to the osteoporotic microenvironment, eventually regulating the biological behavior of mesenchymal stem cells and osteoclasts and improving the osteogenesis at the titanium interface under osteoporotic conditions. We will systematically investigate the stability of the composite titanium surface, loading capacity of the bioactive molecules and retention of their bioactivity, as well as to further studyelucidating the interaction between the cells and the interface and the bone repairing effect for osteoporotic fractures, thus elucidating the regulating mechanisms from molecule and cell levels, which could be indicative for the development of titanium materials capable of bone induction and treatment.

骨质疏松症患者骨密度低、脆性大，其骨折部位和内固定植入物（如钛植入体）之间不能建立快速、稳定的骨键合，易导致骨折修复失败。本项目依据骨质疏松骨组织微环境（局部酸性微环境、高浓度组织蛋白酶k）及骨质疏松环境中骨髓间充质干细胞的特征（低募集性、低成骨性），拟构建具有骨质疏松微环境响应性的钛植入体复合界面，有序释放趋化因子SDF-1α、抗骨质疏松症药物（阿伦磷酸钠）及骨诱导分子（如17β-雌二醇），调控骨髓间充质干细胞及破骨细胞的生物学行为，促进骨质疏松性环境中钛基界面骨生成。系统研究钛基复合界面的稳定性、功能分子的负载量及活性保持性能，深入探索该界面系统与细胞相互作用机制及其对骨质疏松性骨折修复效应，进而从细胞、分子水平探讨、阐释其调控机理，为开发兼具骨诱导性及治疗功效的钛基材料奠定基础。

骨质疏松症患者骨密度低、脆性大，其骨折部位和内固定植入物（如钛植入体）之间不能建立快速、稳定的骨键合，易导致骨折修复失败。本项目依据骨质疏松骨组织微环境（局部酸性微环境、高活性氧和高蛋白酶等）及骨质疏松环境中骨髓间充质干细胞的特征（低募集性、低成骨性），构建了系列具有骨质疏松微环境响应性的钛植入体复合界面，有序释放募集因子、抗骨质疏松症药物及骨诱导分子，调控骨髓间充质干细胞及破骨细胞的生物学行为，促进骨质疏松性环境中钛基界面骨生成。同时，本项目系统研究了钛基复合界面的稳定性、功能分子的负载量及活性保持性能，发现该活性界面能够募集植入组织周围的干细胞并促进其成骨分化，提高骨质疏松性骨折的生物修复效应。该项目从细胞、分子水平上，阐释了骨质疏松微环境响应性的钛植入体复合界面的成骨调控机理，在Biomaterials、Acta Biomater、Appl Mater Today和Chem Eng J等杂志以第一作者/通讯作者发表13篇SCI研究论文和2个授权发明专利，研究成果有望用于开发兼具骨诱导性及治疗功效的钛基植入体。