Mechanisms of magnesium oxide-incorporated electrospun membrane modulating inflammation and accelerating wound healing.

Previously, we demonstrated that magnesium oxide (MgO)-incorporated electrospun membranes show powerful antibacterial activity and promote wound healing, but the underlying mechanisms have not been entirely understood. Herein, we investigated the relationship between structure and function of MgO-incorporated membranes and interrogated critical bioactive cues that contribute to accelerated wound healing and functional restoration. Our results show that MgO-incorporated membranes exhibit good flexibility and improved water vapor transmission rates (WVTRs) and sustained Mg2+ release in a simulated model of wounds. MgO-incorporated membranes modulate macrophage phenotype to downregulate inflammatory response, contributing to alleviated inflammation and creating a favorable microenvironment for wound healing. Specifically, MgO-incorporated membranes stimulate macrophages to shift to a pro-healing M2 phenotype and upregulate pro-healing cytokine of transforming growth factor-beta 1 (TGF-β1) and downregulate pro-inflammatory cytokines under lipopolysaccharide (LPS) challenge conditions. Together with increased TGF-β1 by macrophages, MgO-incorporated membranes significantly boost the proliferation of fibroblasts and upregulate collagen production, thus driving granulation tissue formation and wound closure. MgO-incorporated membranes promote angiogenesis by promoting tube formation and upregulating vascular endothelial growth factor (VEGF) production of endothelial cells. Rapid epithelialization of regenerated skin tissue is attributed to the balanced phenotype of keratinocytes between proliferative and terminally differentiated populations. In addition to coordinating keratinocyte phenotype, MgO-incorporated membranes reduce the expression of inflammatory cytokine interleukin 1-alpha (IL-1α) therefore promoting hair follicle regeneration. These data provide mechanisms of MgO-incorporated membranes that inhibit bacterial infection, alleviate inflammation, facilitate extracellular matrix production and epithelialization, and potentiate hair follicle regeneration.