Macrophage-mimetic living hydrogel microspheres capable of generating NO via the cascade reaction between glucose oxidase and horseradish peroxidase for the treatment of diabetic wound infection

The treatment of diabetic wound infections remains a significant challenge. Nitric oxide (NO) generated by macrophage in body is essential for immune defense and wound healing, making it a promising therapeutic agent for wound infections. However, high glucose level in diabetic wound impairs macrophage function. Here, we construct a macrophage-mimetic living hydrogel microspheres capable of producing NO through a glucose-fueled cascade reaction for efficiently eliminating bacterial infection and accelerating the diabetic wound healing. In our design, glucose oxidase (GOx) and horseradish peroxidase (HRP) are covalently immobilized into the polyacrylamide (PAM) hydrogel microsphere containing poly-L-arginine (P-Arg), followed by encapsulating with M1 macrophage membrane (M) to yield PGHA@M with bacteria-targeting ability. In the presence of glucose, PGHA@M possesses remarkable capability to produce H₂O₂, which is subsequently catalyzed by HRP into hydroxyl radicals ( OH). Meanwhile, the embedded P-Arg is oxidized by OH into NO. PGHA@M demonstrates satisfactory antibacterial and antibiofilm properties. Further in vivo experiments verify that PGHA@M can efficiently eliminate the biofilm bacteria and promote the diabetic wound healing. This study provides a potential strategy to simulate M1 macrophage functions via dual enzymatic cascade reactions, and offers a new perspective for the treatment of diabetic wound infections based on living hydrogel microspheres.