Metabolically Programmed Biomass Hydrogel for Phase‐Transition Therapy of Chronic Diabetic Wounds

Abstract Diabetic wound management remains a major clinical challenge due to its pathologically complex microenvironment. ROS play dual roles in healing, enabling antimicrobial activity while requiring timely attenuation to permit tissue regeneration. This spatiotemporal paradox underscores the need for dressings that dynamically regulate ROS. Here, an intelligent hydrogel that enables autonomous wound regulation via phase‐transition therapy is engineered. An acid‐sensitive H 2 S donor is synthesized by conjugating 2‐aminopyridine‐5‐thiocarboxamide to oxidized dextran and integrated with glucose oxidase (GOx)‐loaded carboxymethyl cellulose into an adaptive hydrogel. The material shows strong tissue adhesion, shape adaptability, mechanical resilience (>70% stress retention after 20 cycles), and rapid self‐healing (>90% recovery in 30 min). Under hyperglycemic conditions, GOx‐generated ROS eliminated 98% methicillin‐resistant Staphylococcus aureus within 4 h while acidifying the microenvironment to trigger sustained H 2 S release over 72 h, enhancing M2 macrophage polarization and angiogenesis. This enzyme‐cascaded system establishes a self‐sustaining metabolic circuit that shifts from antibacterial defense to pro‐regenerative modulation, enabling active metabolic intervention in diabetic wounds.