Glucose-Driven LDH@GOx Cascade Nanozymatic Hydrogel with ROS Regulation for Bacteria-Infected Diabetic Wound Healing

Chronic diabetic wounds are often characterized by hyperglycemia, infection susceptibility, and prolonged oxidative stress, facing the clinical challenge of delayed healing. Here, we present a cascade nanozyme-hydrogel platform that addresses these issues by integrating NiAl layered double hydroxide (LDH), glucose oxidase (GOx), and a hyaluronic acid-lipoic acid (HALA) hydrogel. This system independently metabolizes glucose and dynamically modulates the wound microenvironment. GOx catalyzes the conversion of excess glucose into gluconic acid and hydrogen peroxide (H₂O₂), acidifying the local microenvironment. The peroxidase-like (POD-like) activity of the NiAl LDH is activated under acidic conditions, selectively generating strong oxidizing hydroxyl radicals (•OH) for targeted antibacterial action. Once the infection resolves and the glucose levels normalize, the diminishing acidity shifts the system to a reparative mode. The anti-inflammatory properties of the HALA hydrogel scavenge residual reactive oxygen species (ROS) and promote tissue regeneration. In vitro experiments confirm the dynamic glucose- and pH-responsive functional adaptation. In vivo diabetic rat models verify that the LDH-GOx@HALA hydrogel can regulate the microenvironment of wounds in a direction conducive to accelerated healing. This work introduces an environmentally benign strategy of exploiting key pathological factors as endogenous triggers to dynamically reconstruct a healing-favorable microenvironment for intelligent wound management.