Glucose‐Responsive Zn(II)‐Porphyrin COF Adhesive Hydrogels With Dual‐Active Sites and GOX‐Like Activity for Accelerated Wound Healing

Abstract Effective glycemic control is paramount for optimal wound healing in diabetic patients. Traditional antibacterial and anti‐inflammatory treatments, while important, often fall short in addressing the hyperglycemic conditions of diabetic wounds. Therefore, the development of novel therapeutic strategies for accelerating diabetic wound healing has garnered escalating attention. Covalent organic frameworks (COFs) are an emerging class of crystalline porous polymers constructed through strong covalent bonds. Their exceptional structural tunability renders them as an ideal platform for advanced therapeutic applications. Herein, two redox‐responsive Zn(II)‐coordinated porphyrin COF hydrogels are constructed, which demonstrate rapid blood glucose reduction in localized tissues, along with improved angiogenesis, reactive oxygen species (ROS) scavenging, and photothermal antimicrobial capacities within the hyperglycemic blood environment of diabetic patients, thereby effectively controlling infections and concurrently promoting wound healing. Specifically, COFs with built‐in dual active sites, i.e., disulfide or diselenide moieties, can be cleaved by ROS, releasing Zn(II) ions that possess antibacterial and tissue‐repairing properties. Furthermore, the Zn(II)‐porphyrin COF exhibits glucose oxidase (GOX)‐like activity, catalyzing the conversion of glucose into non‐glucose metabolites. This synergistic combination of glucose‐responsive Zn(II) release and GOX‐like activities effectively restores tissue redox balance and improves the wound microenvironment, offering a promising strategy for the diagnosis and treatment of diabetic wounds.