Diabetic wounds are characterized by persistent oxidative stress, chronic inflammation, and impaired angiogenesis driven by hyperglycemia. Here, we developed a glucose-responsive nanozyme hydrogel (MNP@D-CH) composed of moslosooflavone-loaded, polydopamine-coated PLGA nanoparticles embedded in a dynamic network of phenylboronic acid-modified chitosan and dopamine-conjugated hyaluronic acid crosslinked via reversible boronate esters. Under high glucose, the hydrogel disassembles to release nanoparticles on demand. In vitro, MNP@D-CH eliminated > 90 % of reactive oxygen species, doubled fibroblast migration, restored endothelial tube formation to levels comparable to recombinant human VEGF, downregulated pro-inflammatory cytokines (Il6, Il1b, Tnf), and upregulated Vegfa. It also inhibited 90–100 % of Escherichia coli and Staphylococcus aureus . In diabetic mice, the hydrogel achieved 95.67 % wound closure by day 14, significantly outperforming non-responsive controls and a commercial growth factor, with enhanced re-epithelialization, granulation tissue formation, and collagen organization. RNA sequencing revealed that the treatment suppressed IL-17 signaling and activated the PI3K-Akt pathway. These findings demonstrate that a single hydrogel integrating glucose responsiveness, nanozyme-mediated antioxidation, and controlled drug release can effectively overcome the multiple barriers to diabetic wound healing.
He et al. (Mon,) studied this question.