Glucose-Activated Programmed Hydrogel with Self-Switchable Enzyme-Like Activity for Infected Diabetic Wound Self-Adaptive Treatment

Abstract

The defective blood glucose regulation ability of diabetic patients leading to bacterial infection, cellular oxidative stress, and vascular damage results in delayed healing of chronic diabetic wounds. Here, a glucose-activated self-switching enzyme-like activity programmed hydrogel is proposed to provide self-regulated timely intelligent insulin release affected by blood glucose fluctuations, thereby forming feedback blood glucose management and exerting a full-stage wound healing. The hydrogel is composed of Au─MoS₂─phenylboronic acid nanozyme and insulin-loaded nitroimidazole-modified sodium alginate hypoxia-sensitive microcapsules and penylboronic-acid-modified chitosan. It utilizes glucose as a sacrificial agent to generate antibacterial reactive oxygen species by recognizing the hyperglycemia environment, and releasing insulin for blood glucose regulation for up to 12 h with the help of the enzyme-like catalysis-generated hypoxia environment. In a normoglycemia environment, the hydrogel switches the enzyme-like activity to supply oxygen, inhibiting further insulin release. The hydrogel achieves ≈3 times the wound recovery rate of commercial dressings through blood glucose regulation and improved wound microenvironment. The hydrogel has been proven to significantly improve the healing of chronic diabetic wounds by regulating the body's blood glucose homeostasis and implementing a staged healing treatment plan, providing a powerful solution for diabetic wound care.