Bioinspired antioxidative HA-CPA hydrogels for restoring cellular and vascular function in diabetic wound repair.

Abstract

Chronic diabetic wounds are difficult to treat because persistent oxidative stress, mitochondrial dysfunction, and impaired stromal-vascular communication jointly delay tissue repair. In this study, we developed a bioinspired hyaluronic acid-catechol-PEG-amine (HA-CPA) hydrogel through dynamic Schiff-base crosslinking for topical diabetic wound management. The HA-CPA hydrogel formed a porous, self-supporting network and showed favorable cytocompatibility and hemocompatibility. Owing to catechol-containing moieties, the hydrogel displayed strong antioxidant activity, with more than 80% radical-scavenging efficiency in DPPH and ABTS assays. Under diabetic-mimicking conditions, HA-CPA hydrogel extracts reduced intracellular reactive oxygen species, helped preserve mitochondrial membrane potential, and improved fibroblast migration and endothelial angiogenic behavior, including tube formation. In a streptozotocin-induced diabetic full-thickness wound model, HA-CPA treatment accelerated wound closure, enhanced collagen deposition, and promoted re-epithelialization without detectable systemic toxicity in major organs. These findings indicate that HA-CPA hydrogel provides a practical wound-dressing platform that combines redox regulation, inflammatory microenvironment modulation, cellular protection, and vascular-supportive activity.