Nitric oxide donor-modified extracellular matrix hydrogel loaded with salvianolic acid B for diabetic wound healing

Nitric oxide (NO) donor-based gas therapy has been widely explored to promote angiogenesis in diabetic wound treatment, particularly to compensate for insufficient endogenous NO levels in damaged tissues. Here, we present a skin-derived extracellular matrix (ECM)-based platform that leverages its inherent biocompatibility and cell affinity for efficient NO delivery. An NO donor was chemically grafted onto the ECM scaffold, which was subsequently processed into a hydrogel (H@ECM-SNO/Sal-B) capable of encapsulating salvianolic acid B (Sal B), a bioactive phytochemical with pro-healing potential. This dual-functional system is designed to enhance vascular regeneration and modulate inflammatory responses within the diabetic wound microenvironment. The resulting hydrogel exhibited favorable gelation properties and sustained release of both NO and Sal B. In vitro studies demonstrated that H@ECM-SNO/Sal-B significantly enhanced human umbilical vein endothelial cell proliferation, migration, and tube formation, indicating an enhanced pro-angiogenic effect of the combined formulation. In vivo, the hydrogel accelerated wound closure, reduced inflammatory infiltration, promoted epidermal regeneration, and enhanced collagen deposition. Furthermore, it markedly upregulated the expression of angiogenesis-related markers, including hypoxia-inducible factor-1α (HIF-1α) and CD31, confirming its ability to stimulate neovascularization. By leveraging ECM as a bioactive NO carrier, this hydrogel platform enables the combined delivery of NO and Sal B, providing a multifunctional strategy for promoting diabetic wound healing.