M2型巨噬细胞早期靶向富集促内源性再生的骨修复支架构建及其材料生物学效应

巨噬细胞介导的炎症微环境深刻影响骨缺损修复过程与质量，其M1/M2极化表型与分泌功能可塑性是调控炎症微环境的关键。早期炎症过程中巨噬细胞向M2表型极化有助于促再生修复微环境形成。基于此，围绕“调控炎症微环境，促骨再生效能”这一研究思路，本项目以巨噬细胞可塑性为切入点，结合M2pep多肽的M2型巨噬细胞靶向亲和性，构建可有效富集M2型巨噬细胞的多级结构介孔生物活性玻璃支架MBG-M2pep。以期提高支架-损伤区域M2型巨噬细胞浸润丰度，促进炎症微环境转化，介导增强骨组织内源性修复。并通过系统的体内外模型评价，辨析该“原位靶向富集策略”较“细胞因子极化诱导策略”的差异性；揭示M2型巨噬细胞原位富集所形成的材料-细胞-因子微环境调控巨噬细胞生物学行为的重要规律；阐明其介导的炎症微环境调控间充质干细胞募集分化、血管新生的关键机制。为新型骨修复材料的设计、制备和材料生物学效应研究提供研究基础。

Macrophages-mediated inflammatory microenvironment plays critical roles on the process and quality of bone regeneration. The heterogeneous population of macrophages and their related M1/M2 phenotypes as well as secretion function are considered to be the primary regulators of inflammatory response. Promoting the phenotypic transition towards M2 phenotype has been demonstrated to facilitate the pro-healing microenvironment formation. Based on the principles of “regulating inflammatory microenvironment, thereby enhancing endogenous bone regeneration”, we propose a biofunctional MBG-M2pep scaffold based on hierarchically mesoporous bioactive glass (MBG) and M2 macrophage high binding affinity peptide of M2pep. Combining the specific bind affinity of M2pep with M2 macrophage, the scaffold can increase the enrichment of M2 macrophages in the damaged areas, mediate the immune responses during the early stage inflammation, and further stimulate the endogenous bone formation. Systematically, we will explore the in-vivo biologic differences and regeneration outcomes between the “in situ M2 macrophages enrichment strategy” and the “cytokine-induced polarization strategy”, reveal the relationship between macrophages, mesenchymal stem cells and endothelial cells, and further illuminate the key factors during the inflammation-mediated bone healing. We hope that the concepts proposed in this study might provide new thoughts on development of future orthopedic biomaterials.