Rosmarinic acid-derived micelles potentiated dextran hydrogel for concurrent mechanical reinforcement and inflammatory microenvironment remodeling in chronic diabetic wound healing

The management of chronic diabetic wounds remains a great clinical challenge due to heightened oxidative stress and persistent inflammation. Although antioxidant hydrogels have shown promising therapeutic potential, many suffer from inadequate mechanical performance. Here, a natural rosmarinic acid-derived micelles potentiated dextran hydrogel was designed for chronic diabetic wound treatment. The hydrogel was crosslinked by acrylate-polyethylene glycol-modified rosmarinic acid (AR) micelles, double bonds and phenylboronic acid-modified dextran (DMP), acrylamide (AM), and polyvinyl alcohol (PVA). AR micelles not only imparted antioxidant properties to the hydrogel but also improved the mechanical performance by acting as crosslinkers and energy dissipation points. In addition, the dynamic phenylborate bonds formed by the phenylboronic acid groups on dextran and the cis -diols on PVA further enhanced the antioxidant and mechanical properties of the hydrogel. The AR/PAM/DMP/PVA (APDP) hydrogel exhibited good biocompatibility, ROS scavenging capacity, and anti-inflammatory property in vitro . More importantly, the APDP2 hydrogel effectively accelerated chronic diabetic wound healing by promoting macrophage polarization to the anti-inflammatory M2 phenotype, boosting anti-inflammatory cytokine secretion, as well as facilitating angiogenesis and collagen deposition. Thus, the rosmarinic acid-derived micelles crosslinked hydrogel presents a promising strategy for the treatment of diabetic wounds and provides new insights for developing herbal functionalized hydrogel materials.