聚多巴胺介导HBPL修饰骨粉调控微环境促进感染骨缺损修复的作用及机制研究

因口腔环境复杂，植骨需常规进行抗感染治疗。然而，临床上广泛存在糖尿病、牙周炎等导致的术区急、慢性感染，且目前国内外缺乏具有抗菌性能的骨替代产品，增加了骨缺损修复的感染风险。申请人前期研究发现HBPL化学接枝的钛表面具有抗菌、促成骨的双重功能，且上调了Integrin的表达（发表于Biomaterials）。结合Integrin-FAK是调控植入微环境的关键通路，提出假说：聚多巴胺介导HBPL修饰的骨粉通过Integrin-FAK信号轴调控巨噬细胞的极化，促进间充质干细胞成骨向分化。本项目将通过一系列表征、体外及体内实验，明确材料构建成功并评估其抗菌、抗炎、促成骨性能；通过高通量测序、分子生物学实验探索HBPL修饰的骨粉对植入微环境的调控及巨噬细胞与干细胞间作用的机制。该项目将有助于进一步阐释免疫调节与组织重建的关系，有望研制出减少抗生素预防性使用、提高患者生活质量的新型骨替代材料。

Because the oral cavity is a complex environment with multiple florae, patients who need bone transplantation need routine anti-infective treatment. And clinically, there are widespread acute and chronic infections in the operation area caused by trauma, diabetes, periodontitis, etc., which increase the risk of bone defect repair. However, the current domestic and foreign markets lack bone substitute materials with antibacterial properties. Our previous research found that the titanium surface modified by HBPL has the dual functions of antibacterial and osteogenesis, and up-regulated the expression of Integrin (published on Biomaterials，IF: 10.317). Combining that Integrin-FAK signal axis is a key pathway to regulate the implantation microenvironment, we hypothesize that polydopamine mediated HBPL-modified bone grafts can regulate the polarization of macrophages through the Integrin-FAK signal axis, and promote osteogenic differentiation of mesenchymal stem cells. This project will use a series of characterization, in vitro and in vivo experiments to clarify the success of the material construction and evaluate its properties of antibacterial, anti-inflammatory, and osteogenesis. Furthermore, high-throughput sequencing and molecular biology experiments would be employed to explore the regulation of HBPL-modified bone grafts on the implantation microenvironment and the mechanism of the interaction between macrophages and stem cells. This project improves further understanding of the relationship between immune regulation and tissue reconstruction. In terms of clinical transformation, the project is expected to develop new bone substitute materials that reduce the preventive use of antibiotics and improve the quality of life of patients.