激活自噬促骨质疏松性骨缺损修复生物陶瓷的设计与机制研究

骨质疏松症（Osteoporosis, OP）属严重的退行性疾病，易引发骨折、骨缺损和高致残率。OP内环境的持续氧化应激状态引发了炎性微环境、并降低了骨髓间充质干细胞（BMSCs）的归巢和成骨向分化能力。现有材料难以适配OP的内环境生理功能，导致临床使用效果不佳。我们预实验发现：特定结构和组成的生物陶瓷能够激活OP来源BMSCs自噬响应，以缓解氧化应激反应、并形成促细胞成骨分化的生物学现象；但材料特性和相关机制尚不明确。本项目旨在通过生物陶瓷优化设计，实现材料自身微纳结构良好介导OP内源性BMSCs归巢至植入材料部位；通过微纳结构，尤其是陶瓷降解释放的活性离子形成持续激活细胞自噬响应，以缓解缺损部位的氧化应激反应、形成促进BMSCs成骨分化的应激适应微环境；并揭示材料表面微纳结构、活性元素及其之间的协同激活自噬调控骨质疏松性骨缺损修复的规律和生物学机制，具有重要的科学意义和临床应用价值。

Osteoporosis (OP) is a serious degenerative disease that can lead to fractures, bone defects and high rates of disability. The continuous oxidative stress in the internal environment of OP induces inflammatory microenvironment and reduces the homing and osteogenic differentiation abilities of bone marrow mesenchymal stem cells (BMSCs). The existing materials are difficult to regulate the physiological functions of the internal environment of OP, resulting in poor clinical application effects. In our preliminary experiments, the biological phenomena of the specific structure and composition of bioceramics that can activate the autophagy level of BMSCs derived from OP to alleviate the oxidative stress response and stimulate osteogenic differentiation were found. However, the material characteriistics and the behind mechanisms are still unclear. The purpose of this project is to achieve the optimal designing of bioceramics to mediate the homing of endogenous BMSCs in OP, and regulate their osteogenic differentiation. At the same time, the bioactive ions released from the degradation of bioceramics can continuously activate the autophagy level, so as to alleviate the host's oxidative stress response and form stress adaptive microenvironment for the promotion of osteogenic differentiation of BMSCs. Moreover, the study will reveal the laws and biological mechanisms among the micro-/nano-structured surfaces and bioactive elements of bioceramics, and their synergistic activation of autophagy to regulate the repair of osteoporotic bone defects. The present project plays an important theoretic and clinical application role in the designing and development of bioactive materials for osteoporotic bone defect repair.