Clinically, abnormal or delayed wound healing leads to functional disorders and disfiguring scars. A well-vascularized environment and an anti-inflammatory immune state are crucial during the healing process. Molybdenum (Mo) is an essential element for the human body in modulating metabolism, immune function and tissue repair. In this study, we found that Mo-inspired macrophages significantly promoted the proliferation, migration, tube formation, and the expression of angiogenic factors (VEGF, PDGF, CD31) in human umbilical vein endothelial cells (HUVECs). We then successfully isolated and characterized Mo-inspired macrophage-derived exosomes (Mo-Exo) and demonstrated their internalization by HUVECs, leading to enhanced proliferation, migration, tube formation, and angiogenic factor expression. Moreover, we proved that Mo-Exo could promote the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. In terms of application, Mo-Exo encapsulated gelatin methacryloyl hydrogel (GelMA) exhibited notable potential in wound healing in rat skin defects, as evidenced by the reduced wound area and increased epidermal thickness observed in H&E and Masson's staining. Mechanically, Mo-Exo promoted angiogenesis through the activation of the ERK1/2 signaling pathway. In general, this research introduced a novel immunoregulatory and pro-angiogenic exosome hydrogel for clinical wound healing.
Keywords: Angiogenesis; Exosome; Gelatin methacryloyl; Molybdenum; Wound healing.
Copyright © 2024. Published by Elsevier B.V.