Metabolic microenvironment self-adaptive cobalt-based hydrogel dressing sustains spatiotemporal ROS generation for chronic diabetic wound repair

Chronic refractory wounds in diabetic patients pose a substantial clinical challenge owing to fluctuating pH levels, bacterial infections, and compromised healing mechanisms. Here, we have developed a metabolic dynamic self-adaptive cobalt-based hydrogel dressing that incorporates spatially confined biomineralized enzyme (glucose oxidase) nanoflowers with high catalytic efficiency and a polyvinylpyrrolidone (PVP) hydrogel matrix with superior unidirectional water absorption capacity. The elevated glucose metabolism in diabetic wounds was harnessed to enable efficient cascade catalysis to convert glucose into hydrogen peroxide (H 2 O 2 ), followed by Co 2+ /Co 3+ redox reactions that sustain spatiotemporal reactive oxygen species (ROS) generation. The low redox potential of the cobalt hydrogel allows robust catalytic activity (>75%) across a wide pH range (4.0–9.0) for over 50 h to adapt to the entire process of wound repair. Moreover, the hydrogel reduces the diffusion distance between ROS and bacteria, resulting in potent broad-spectrum antibacterial activity, including biofilm eradication, against multidrug-resistant Escherichia coli , Pseudomonas aeruginosa , and methicillin-resistant Staphylococcus aureus (MRSA). In an immunosuppressed mouse model of diabetic trauma, it was demonstrated that under hyperglycemic conditions, the GCP hydrogel facilitated a wound closure rate of 97.4% by day 12. Our strategy paves the way for the development of advanced intelligent wound dressings featuring dynamic, self-adaptive microenvironments and persistent antimicrobial activity.