OPN和BSP对骨内植入材料界面巨噬细胞免疫响应的调控

骨内种植体植入体内早期反应的主导细胞是巨噬细胞。与聚合物-骨界面的巨噬细胞持续存在与融合不同，钛-骨整合界面早期的巨噬细胞则快速消失。钛植入骨内后先形成OPN和BSP为主的粘合线蛋白层，而OPN和BSP可介导巨噬细胞在钛表面的黏附。近期体外研究和本课题组预实验显示，OPN和BSP可影响巨噬细胞的融合与生存。因此，本项目提出，OPN和BSP很可能通过影响巨噬细胞表型、融合和凋亡，而对钛-骨界面的巨噬细胞免疫响应发挥调控作用。本课题拟从体内和体外实验两种角度来验证假设，首先在不同动物模型中观察OPN和BSP在植入材料界面对巨噬细胞分布和转归的影响。然后在体外细胞学实验中，观察OPN和BSP对巨噬细胞M1/M2表型、凋亡、融合的影响及其可能机制。本项目将粘合线蛋白对巨噬细胞免疫应答的调控作为材料界面研究的新切入点，来探寻生物材料的免疫响应机制，这将为植入材料的改性开辟新的设计思路。

Macrophages play a predominant role in the bone after the titanium implants are inserted. The macrophages of bone-polymer interface constantly exist and fusion in a long term, macrophages in bone-titanium integration interface disappear quickly. After titanium implantation in the bone, a cement line mainly consisted with osteopontin (OPN) and bone sialoprotein (BSP) protein forms first, OPN and BSP protein might mediate macrophages adhesion in titanium surface. Recently in vitro research and pilot trials indicated that OPN and BSP might influence macrophages fusion and survival. Therefore, this project proposes that OPN and BSP are likely to mediate macrophages immune response via their impact on macrophage viability in bone-titanium interface.. This study involves in vivo and in vitro experiments and aims to test these hypotheses. Firstly, OPN and BSP expression in bone-implant interface will be detected in different animal models, while their influence to the spatial and temporal distribution and outcome of macrophages and foreign body giant cells will also be studied. And then the in vitro experiments attempt to observe the impact of OPN and BSP to macrophages phenotype M1/M2, apoptosis, fusion and other biological activity as well as their possible mechanism. As the breakthrough point is that the proteins within the cement line mediate the macrophages immune response in bone-implant interface, this project aims at exploring the immune response mechanism in medical implantation, which will introduce a new design idea for the implant material modification.