巨噬细胞极化
细胞生物学
骨愈合
巨噬细胞
间充质干细胞
炎症
再生(生物学)
M2巨噬细胞
材料科学
化学
癌症研究
免疫学
体外
医学
生物
生物化学
解剖
作者
Xianzhong Dai,Boon Chin Heng,Yunyang Bai,Fangtian You,Xiaowen Sun,Yiping Li,Zhangui Tang,Mingming Xu,Xuehui Zhang,Xuliang Deng
标识
DOI:10.1016/j.bioactmat.2020.12.020
摘要
Macrophage-mediated inflammation compromises bone repair in diabetic patients. Electrical signaling cues are known to regulate macrophage functions. However, the biological effects of electrical microenvironment from charged biomaterials on the immune response for regulating osteogenesis under diabetic conditions remain to be elucidated. Herein the endogeneous electrical microenvironment of native bone tissue was recapitulated by fabricating a ferroelectric BaTiO3/poly (vinylidene fluoridetrifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite membrane. In vitro, the polarized BaTiO3/poly (vinylidene fluoridetrifluoroethylene) (BTO/P(VDF-TrFE)) nanocomposite membranes inhibited high glucose-induced M1-type inflammation, by effecting changes in cell morphology, M1 marker expression and pro-inflammatory cytokine secretion in macrophages. This led to enhanced osteogenic differentiation of human bone marrow mesenchymal stem cells (BM-MSCs). In vivo, the biomimetic electrical microenvironment recapitulated by the polarized nanocomposite membranes switched macrophage phenotype from the pro-inflammatory (M1) into the pro-healing (M2) phenotype, which in turn enhanced bone regeneration in rats with type 2 diabetes mellitus. Mechanistic studies revealed that the biomimetic electrical microenvironment attenuated pro-inflammatory M1 macrophage polarization under hyperglycemic conditions by suppressing expression of AKT2 and IRF5 within the PI3K-AKT signaling pathway, thereby inducing favorable osteo-immunomodulatory effects. Our study thus provides fundamental insights into the biological effects of restoring the electrical microenvironment conducive for osteogenesis under DM conditions, and offers an effective strategy to design functionalized biomaterials for bone regeneration therapy in diabetic patients.
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