Scheme 1.

Illustration of how electric microenvironment promotes osteogenesis in diabetes mellitus by modulating macrophage polarization. After corona poling treatment, the surface of the ferroelectric nanocomposite membrane displays induced charges. Within the electrical microenvironment, macrophages exhibit less M1 polarization and more M2 polarization. The polarized nanocomposite membranes downregulate AKT2-IRF5 signaling that induces macrophages to the M2 phenotype, which indicates a favorable osteo-immunomodulatory environment. Hence mimicking the endogeneous electrical microenvironment promotes osteogenic differentiation of BM-MSCs mediated by macrophages, thereby improving bone regeneration. The purple arrow denotes the osteogenesis of BM-MSCs. The grey arrows denote the suppressed M1 phenotype of macrophages. The red arrows denote the downregulated expression of AKT2 and IRF5, and improved M2 phenotype of macrophages.