A Glucose‐Responsive Intelligent Antibacterial and Oxygen‐Producing Hydrogel Promotes the Healing of Diabetic Wounds by Regulating Cellular Heterogeneity

ABSTRACT The chronic and refractory infected wounds of diabetes are primarily attributed to the persistent bacterial infection and the inhibition of wound healing caused by hypoxia. Hydrogel with intelligent drug delivery systems hold significant potential in the treatment of diabetic wounds. Herein, we have developed an glucose‐responsive intelligent hydrogel named as CF‐CPGaMPN, which incorporates polyvinylpyrrolidone‐coated calcium peroxide (PVP@CaO 2 ) nanoparticles, catalase, and gallium‐polyphenol (GaMPN) nanoparticles. The borate ester bonds in the CF‐CPGaMPN hydrogel break under high glucose conditions, releasing GaMPN nanoparticles, thereby achieving glucose‐triggered on‐demand drug release. The CF‐CPGaMPN hydrogel not only inhibits various microorganisms but also continuously releases oxygen, thereby promoting the healing of diabetic infection wounds. Furthermore, the multicellular ecosystem surrounding the CF‐CPGaMPN hydrogel is also explored, and the diverse cellular heterogeneity is analyzed by single‐cell RNA sequencing, highlighting the critical roles of Neutrophils, Fibroblasts, and Epidermal cells in diabetic infected wound. In addition, CF‐CPGaMPN hydrogel inhibits the Neutrophil extracellular trap (NET) formation and alleviates the cellular hypoxic environment to improve diabetic wound healing. In conclusion, the CF‐CPGaMPN hydrogel not only provides a promising drug release strategy for the healing of diabetic infected wounds, but also contributes to the rational design of customized hydrogels for biomedical use targeting different cellular functions.