Oxygen‐Vacancy‐Engineered Self‐Regenerative Nanozymes in Dual‐Signal‐Responsive Dynamic Hydrogels: A Closed‐Loop Therapeutic Strategy for Diabetic Wound Microenvironment Remodeling

Abstract Diabetic wounds are trapped in a self‐perpetuating pathological triad of hypoxia, infection, and oxidative stressdisrupting physiological wound healing and causing recalcitrant nonhealing ulcerswhile conventional therapies, limited by static interventions and simplistic co‐delivery, fail to adapt to the spatiotemporally heterogeneous wound microenvironment and break this cycle; to address this, we engineered a microenvironment‐responsive closed‐loop hydrogel dressing by integrating Cu‐doped oxygen‐vacancy molybdenum oxide nanozymes (MoO 3− x (Cu)) and curcumin (Cur) into an oxidized alginatehyaluronic acid matrix: MoO 3− x (Cu) forms a self‐regenerative defect synergy via Mo 5+ /Mo 6+ ‐Cu + /Cu 2+ dual redox cycles (oxygen vacancies (Vo) regenerate Cu 2+ →Cu + , Cu + stabilizes Vo, decomposing 98.7% endogenous H 2 O 2 into O 2 in 24 h with sustained catalysis), Cur acts as a catalytic cofactor (chelating Cu 2+ ) and antimicrobial (disrupting bacterial membranes) for > 99.9% biofilm inhibition, and the pH‐responsive Schiff base‐crosslinked hydrogel (activated by diabetic wounds' alkaline pH 79) accelerates Schiff base hydrolysis to release nanozymes/Cur and boost MoO 3− x (Cu)'s catalytic efficiency by 1.8‐fold, dynamically matching wound microenvironment demands.