Zinc ions coordinated carboxymethyl chitosan hydrogel doped with ellagic acid for accelerative diabetic wound healing

Diabetic wound healing remains a critical clinical challenge due to persistent inflammation derived from long-term hyperglycemia. To address this challenge, we reported a zinc ion coordinated CMCS hydrogel for pH responsive delivery of ellagic acid to fulfill diabetic wound management. The incorporation of zinc ions and EA reinforce the hydrogel network via coordination and hydrogen bonding, and confer a pH-responsive release of EA under simulative wound microenvironment. CMCS-Zn@EA hydrogel exhibited substantial scavenge capacity against multiple oxidative species (·OH and ABTS), which may protect fibroblasts from oxidative damage, and thereby promoting cellular migration and angiogenesis. Further investigation on diabetic wound models revealed that the topical administration of CMCS-Zn@EA effectively accelerated the wound healing ratio through promoting angiogenesis, re-epithelialization, and collagen deposition. Moreover, the incorporation of Zn²⁺ into the hydrogel framework through coordination bonding dynamically aligned with the whole wound healing phases to modulate macrophage polarization and thus providing a more favorable environment for the wound healing. Together with the great biocompatibility, CMCS-Zn@EA hydrogel may hold great potency to be applied in the clinical diabetic wound management.