载锶仿生磷酸钙涂层调控巨噬细胞极化促进糖尿病颅颌面骨再生的研究

糖尿病局部促炎环境导致骨缺损愈合障碍。赋予骨替代材料骨免疫微环境调控特性，可调控巨噬细胞极化降低局部炎症促进骨再生，应用此类材料修复糖尿病骨缺损已成为研究热点。载锶骨替代材料具有促进成骨分化、抑制破骨分化和骨免疫微环境调控多重特性，且研究表明钙敏感受体介导的信号通路在其促成骨、抑破骨过程中发挥主要作用。申请人发现锶可降低脂多糖诱导的炎症反应，且载锶骨替代材料促进骨质疏松骨缺损修复。但其在骨免疫中调控巨噬细胞极化的机制仍未明确，且其在糖尿病骨再生中的效果仍未知。因此申请人提出载锶骨替代材料可通过钙敏感受体介导的信号通路调控巨噬细胞极化，间接促进成骨分化，进而促进糖尿病骨再生。本项目拟构建载锶仿生磷酸钙涂层，体外实验明确其调控巨噬细胞极化的机制，筛选并验证其调控巨噬细胞极化间接促进成骨的关键细胞因子及信号通路，体内实验研究其促进糖尿病颅骨和牙周骨缺损修复的能力，为糖尿病颅颌面骨再生提供新方案。

The local pro-inflammatory environment of diabetes leads to bone defect healing disorder. Endowing bone substitutes with osteoimmunomodulatory properties can regulate macrophage polarization, reduce local inflammation and promote bone regeneration. The application of such materials to repair diabetic-related bone defects has become a research hotspot. Strontium loaded bone substitutes have many characteristics, such as promoting osteogenic differentiation, inhibiting osteoclast differentiation, and modulating the osteoimmune environment. Studies have shown that the calcium-sensitive receptor mediated signaling pathway plays a major role in the process of promoting osteogenic differentiation and inhibiting osteoclast differentiation. The applicant previously found that strontium can reduce LPS induced inflammatory response, and strontium loaded bone substitutes can promote osteoporotic bone regeneration, but the relevant mechanism of macrophage polarization in osteoimmunomodulation is still unclear, and its role in diabetic-related bone regeneration remains to be studied. Therefore, the applicant proposes that strontium loaded bone substitutes can regulate macrophage polarization through calcium-sensitive receptor mediated signaling pathway, indirectly promote osteogenic differentiation, and then promote diabetic bone regeneration. This project intends to construct strontium loaded biomimetic calcium phosphate coating, clarify its mechanism of regulating macrophage polarization through in vitro experiments, screen and verify the key cytokines and signal pathways that indirectly promote osteogenesis by regulating macrophage polarization, and study its ability to promote the repair of the diabetic-related skull and periodontal bone defects through in vivo experiments. This project will provide new methods for bone regeneration of craniofacial bone defects in diabetes mellitus.