An in situ-forming hydrogel with a sol-spray system promotes diabetic wound healing via synergistic anti-inflammatory and antioxidant effects.

Chronic diabetic wounds remain a substantial clinical challenge, largely attributable to sustained inflammation, excessive oxidative stress, and deficient tissue regeneration. Herein, an in situ-forming hydrogel fabricated using a dual-component sol-spray system (AGBS-IG) is designed to effectively modulate the inflammatory-oxidative microenvironment and accelerate diabetic wound healing. The injectable sol component, composed of sodium alginate, polyvinyl alcohol, and itaconic acid, enables conformal filling of irregular wound beds and provides intrinsic anti-inflammatory activity, while the spray component, containing calcium ions and gallic acid, rapidly cross-links to form a cohesive hydrogel surface with potent antioxidant and protective functions. The resulting hydrogel exhibits a porous internal network for efficient exudate absorption and nutrient exchange, together with a smooth outer membrane that provides a physical barrier to maintain a moist wound environment. In vitro studies demonstrate excellent biocompatibility, effective reactive oxygen species scavenging, suppression of pro-inflammatory cytokines, facilitated a shift in macrophage polarization toward the reparative M2 phenotype, and enhanced endothelial and fibroblast migration and proliferation. In the diabetic mouse model, AGBS-IG significantly accelerates wound healing, re-epithelialization, collagen remodeling, and restoration of skin appendages, while reducing oxidative stress and advanced glycation end products. Collectively, this work presents a highly adaptable sol-spray hydrogel platform with practical potential for diabetic wound therapy.