An Adhesive Multifunctional Hydrogel for Sequential Anti-inflammatory, Antioxidant, and Pro-regenerative Diabetic Wound Therapy.

Abstract

Diabetic wound healingAC: remains challenging due to persistent inflammation, oxidative stress, and impaired macrophage polarization. Herein, a multifunctional hydrogel dressing was constructed from carboxymethyl chitosan and oxidized dextran as the dynamic network, incorporating CeO2 nanozymes for early anti-inflammatory and antioxidant effects and PLGA microspheres loaded with astragaloside IV for sustained pro-regeneration. Via Schiff base crosslinking, this hydrogel self-assembled rapidly at room temperature and adhered tightly to tissue. In vitro, the hydrogel exhibited excellent biocompatibility, potent antioxidant and anti-inflammatory activities, and promoted endothelial cell migration and angiogenesis. In a diabetic rat full-thickness wound model, this hydrogel dressing effectively reduced local inflammation, drove macrophage polarization toward the M2 phenotype, and enhanced neovascularization to accelerate wound closure. RNA sequencing further revealed that inflammatory pathways, including TNF and IL-17 signaling, were suppressed while tissue regeneration programs were activated. This stepwise therapeutic strategy offers a promising alternative for diabetic wound repair.