硅酸钙复合β-磷酸三钙生物陶瓷调节巨噬细胞极化方向促进骨修复的机制

Regulation of macrophage polarization direction, induction of macrophage phenotypic balance from proinflammatory M1 to reparative M2 and gaining a goal to optimize the host response to bone prosthesis is a new direction for bone repair material technology. The project is based on the forefront of bone repair material research and aims at the clinical problem. We plan to composite β-TCP with CS in different proportions as a breakthrough point, and design, fabricate composite bioceramic in different proportions. In the present project, the influence of the Si element on variety cell types in microenvironment of bone defect site will be investigated. Further, the relationship between the cells treated by Si and M2 polarization direction will be disclosed. Under the conditions of the different composite proportion, Si element release patterns will be studied and the optima concentration of Si element regulating the balance of M1 to M2 will be sought, through exploring the effects of M1/M2 balance and bone repair. Several cell signal pathways driving macrophage polarization direction and the impact of the composite bioceramics on the signal pathway will be illuminated. Ultimately, a way to impair pathological inflammation though regulating macrophage function by composition composited will be explored, providing new thought for research, development, evaluation and application of new bone repair materials.

如何调控巨噬细胞极化方向，诱导其从促炎症表型M1至促修复表型M2极化，以达到人体对骨修复体的最佳生物学反应，是骨修复材料技术领域的新方向。本项目立足于骨缺损修复材料研究前沿，瞄准临床存在问题，通过向β-TCP中复合不同比例的CS为切入点，设计制备不同组成比例的复合生物陶瓷：研究Si元素对于骨缺损微环境中多种细胞的影响，发现Si元素通过这些细胞对于巨噬细胞M2极化方向的引导关系；寻找不同复合比例条件下Si元素的释放规律，通过研究不同Si元素的释放量所诱导的巨噬细胞M1/M2极化比例与促骨修复作用的效应，明确Si元素调控巨噬细胞M1/M2极化平衡的最佳释放浓度；引入多条与巨噬细胞M1、M2方向极化的信号传导途径，揭示复合陶瓷对于信号转导通路中几个关键蛋白成分的作用及相关机制，最终探索一条通过成份复合调节巨噬细胞功能、改善植入后病理性炎症问题的道路，为骨修复材料的研制、开发、评价和应用提供思路。

如何调控巨噬细胞极化方向，诱导其从促炎症表型M1至促修复表型M2极化，以达到人体对骨修复体的最佳生物学反应，是骨修复材料技术领域的新方向。本项目立足于骨缺损修复材料研究前沿，瞄准临床存在问题，通过向β-TCP中复合不同比例的CS为切入点，制备了不同组成比例的复合生物陶瓷，研究了不同复合比例条件下Si元素的释放规律，并揭示了Si元素的释放与骨修复的正相关关系；研究了Si元素对于骨缺损微环境中成骨细胞的影响，进一步发现Si元素诱导成骨细胞表达TGF-β，提示了Si元素与巨噬细胞M2极化的方向的关联性，为进一步的探索研究提供思路。