纤维形貌诱导的巨噬细胞外泌体对骨髓间充质干细胞向成骨分化的作用机制研究

Studies have shown that the M1/M2 polarization and inflammatory secretion of macrophages affect the osteogenic differentiation of osteoblasts. In particular, exosomes from immune cells directly induce MSCs into the osteoblast lineage, but the mechanism has not been fully elucidated. This project is based on the osteoimmunomodulatory role of the surface morphology of the bone regenerative materials. The polarization of macrophages and the subsequent secretion of exosomes on osteogenic induction are used as the breakthrough point. Electrospinning was used to fabricate aligned and random fibers. The fiber topography was used to induce macrophage polarization and secrete different exosomes, as well as their impacts on osteogenic differentiation of bone marrow mesenchymal stem cells and the involved mechanism. The present study explore a pathway of macrophage-derived exosomes induced by scaffold topography to regulate the osteogenic differentiation of bone marrow mesenchymal stem cells. It provides a scientific basis for constructing immune response to regulate bone regeneration, provides a feasible solution for the design of bone biomaterials, and provides new ideas and hopes for the regeneration and repair of bone defects.

研究表明巨噬细胞的M1/M2极化状态和炎性分泌功能会直接影响骨形成细胞的成骨分化。特别是巨噬细胞外泌体可直接诱导MSC进入成骨细胞谱系，但其作用机制尚未完全阐明。本项目立足于材料的表面形貌在骨免疫中的关键作用，以材料诱导巨噬细胞极化及其分泌外泌体对后续成骨分化的调控为切入点，采用静电纺丝法构建有序、无序纤维，利用纤维形貌诱导巨噬细胞极化进而分泌不同的外泌体，研究其对骨髓间充质干细胞的作用机制。探索一条通过材料形貌诱导巨噬细胞极化后分泌的外泌体，调控骨髓间充质干细胞成骨分化的道路。为构建免疫反应调控骨再生提供科学基础，为骨生物材料的设计提供可行的方案，为骨缺损的再生修复提供新的思路和希望。

研究表明巨噬细胞的M1/M2极化状态和炎性分泌功能会直接影响骨形成细胞的成骨分化。特别是巨噬细胞外泌体可直接诱导骨髓间充质干细胞进入成骨细胞谱系，但其作用机制尚未完全阐明。本项目立足于材料的表面形貌在骨免疫中的关键作用，以材料诱导巨噬细胞极化及其分泌外泌体对后续成骨分化的调控为切入点，采用静电纺丝法构建有序、无序纤维模板，利用纤维形貌诱导巨噬细胞极化进而分泌不同的外泌体，进而研究外泌体对骨髓间充质干细胞向成骨分化作用机制。结果表面传统的LPS和IL-4诱导极化相比，巨噬细胞与纤维膜共培养之后，巨噬细胞是M1和M2极化的混合状态，并随着时间的变化而变化。与传统的经典激活巨噬细胞极化相比，最终可能可以实现更好修复效果。体外不同来源外泌体与BMSCs共培养结果显示，不同来源的巨噬细胞外泌体均能在一定程度上诱导BMSCs向成骨分化。探索一条通过材料形貌诱导巨噬细胞极化后分泌的外泌体，调控骨髓间充质干细胞成骨分化的道路。为构建免疫反应调控骨再生提供科学基础，为骨生物材料的设计提供可行的方案，为骨缺损的再生修复提供新的思路和希望。