亲水种植体通过KDR介导的PI3K-Akt-eNOS信号通路促进骨整合早期血管生成的机理研究

获得快速稳定的骨整合一直是口腔种植学研究的目标。亲水种植体可促进成骨细胞早期分化，加速骨整合，已成为近些年的研究热点。然而亲水种植体促进骨整合机理的研究却十分有限。血管系统是维持骨代谢的最基本结构，由于种植手术创伤导致的组织细胞缺血缺氧，无法快速启动骨整合过程，此时必须要由血管内皮细胞（EC）新生毛细血管来强化供应。目前仅有为数不多的研究报道了亲水种植体促进了EC在骨整合早期的血管生成，但研究不够深入，机制仍有待阐明。课题组查阅文献并分析前期工作，猜想亲水种植体可能通过KDR介导的PI3K信号通路促进骨整合早期的血管生成。本课题将进行完整的体内外实验，对比EC在不同钛表面的生物学行为，采用一系列分子检测方法结合KDR的RNA慢病毒干扰技术，探索与分析亲水种植体促进血管生成的机理。本研究力求从分析亲水种植体促进血管生成机理的角度，为亲水种植体促进骨整合理论提供新思路。

The implant with hydrophilic surface shows an advantage of improving activity of osteoblasts and accelerating implant osseointegration, which has always been an important goal of dental implant research. However, the mechanism of promoting osseointegration by the implant with hydrophilic surface is very limited. Blood vessels, as a base of bone formation, are destroyed due to the trauma of implant surgery. In a state of hypoxia, the process of implant osseointegration cannot be started. Endothelial cell (EC), as a base of vascular endothelium, is the crucial cell type involved in angiogenesis and neovascularization. However, limited data were found about the hydrophilic surface can stimulate angiogenesis in human EC and the study is not so complete. And above all, the mechanism of angiogenesis remains to be elucidated. Based on our previous work and the background, we hypothesized that the hydrophilic surface may exert a positive effect to monitor KDR-mediated PI3K-Akt-eNOS signaling pathway, thus stimulating angiogenic activity. To verify this mechanism, we will conduct vitro and vivo experiments. The vitro study aims: (1) at contrasting dynamically the cellular responses of EC on different chemistries of Ti surfaces. (2) and the protein expression level of upstream mediated molecule KDR and downstream pathway of EC. (3) and the protein expression level of downstream pathway after blocking of KDR with lentivirus-mediated KDR RNA interference. In the current experiment, the vivo study aims to analysis and grasp this mechanism of angiogenesis in beagles’ mandibles. This research explores the mechanism for the implant with hydrophilic surface to promote angiogenesis, providing new ideas for improving early osseointegration.