Glucose/ROS/pH Triple Editing “Domino Hydrogel”\nAccelerates Diabetic Wound Healing via Hypoglycemic, Antioxidant,\nAntibacterial, and Macrophage Polarization

Diabetic\nfoot ulcers are a severe complication of diabetes, imposing\na substantial burden on both health and the economy. Bacterial infections,\nhigh glucose levels, and the intricate microenvironment of oxidation\ncollectively hinder the healing of diabetic wounds. Hydrogels responsive\nto the microenvironment have demonstrated significant advantages in\ntreating diabetic wounds due to their ability to release drugs on\ndemand. The study utilized modified pectin and hyaluronic acid to\ndevelop a self-recognizing and self-treating composite hydrogel. Within\nthis hydrogel, insulin was encapsulated using a metal–organic\nframework with an ROS-responsive coating (ZIF-8@PEG-TK). Under high\nglucose and low pH conditions, INS@ZIF-8@PEG-TK was released and responded\nto excess ROS, ensuring sustained insulin release. This hydrogel exhibited\nexcellent antimicrobial and antioxidant activities along with biocompatibility.\nIt promoted the polarization of macrophages, reduced glucose levels,\nand accelerated cell proliferation and collagen deposition, leading\nto rapid wound closure. Accordingly, the microenvironment-responsive\nhydrogel is a promising biomaterial for treating chronic diabetic\nwounds.