SI_Supplementary_Data_Explanation_QCMCS_OSA_TA_STB_Hydrogel.pdf

Diabetic wound repair remains a pressing global healthcare burden, largely attributed to formidable barriers including bacterial infection and a pathological microenvironment defined by hyperglycemia, elevated pH, hypoxia, sustained inflammation, and compromised angiogenesis. To address this unmet clinical need, we have developed a novel hydrogel system comprising quaternized carboxymethyl chitosan (QCMCS), oxidized sodium alginate (OSA), tannic acid (TA), and sodium tetraborate (STB), designed for environment-responsive controlled release of TA to enhance diabetic wound healing. A key advantage of this hydrogel lies in STB-mediated reversible borate linkages with TA’s catechol groups, which effectively protect TA from oxidative degradation under non-wound conditions. Critically, these borate ester bonds are selectively cleavable in the diabetic wound microenvironment—characterized by high reactive oxygen species (ROS) and glucose levels—enabling a "protection–deprotection" activation mechanism that ensures site-specific TA release. Additionally, STB contributes to a dual cross-linking network (integrating borate ester bonds and Schiff base interactions), reinforcing the hydrogel’s mechanical properties while endowing it with excellent self-healing, antibacterial, and antioxidant capacities. This microenvironment-responsive hydrogel offers a promising strategy for advanced diabetic wound management, and we herein submit our work for consideration.