A novel matrix metalloproteinases-cleavable hydrogel loading deferoxamine accelerates diabetic wound healing

The hyperglycemia microenvironment of diabetic foot ulcer (DFU) led to impaired angiogenesis and delayed wound healing. An elevated matrix metalloproteinase (MMP) is one of the significant factors to delay healing. Herein, we designed a deferoxamine (DFO)-loaded MMP responsive hydrogel, thus promoting angiogenesis and accelerating wound healing by increasing the expression of hypoxia-inducible factor-1α (HIF-1α). Hyaluronic acid was modified with maleimide and grafted with MMP-cleavable peptides (HA-peptide). Then, HA-peptide was crosslinked with oxidized dextran (Dex-CHO) based on Schiff-base reaction. In vitro tests showed that the hydrogel had excellent swelling properties, degradation behavior, rheological characterization, and biocompatibility. Compared with an MMP-insensitive hydrogel, the MMP-cleavable hydrogel allowed for efficient release of DFO continuously within 24 h, which could address the problems of the extremely short half-life and neurotoxicity of DFO. In vivo experiments demonstrated that the hydrogel wound dressing facilitated faster wound epithelialization and accelerated angiogenesis in diabetic rats. Altogether, the DFO-loaded MMP-cleavable hydrogel may lead to a potential and novel treatment strategy of DFU.