Dual ROS/Glucose-Responsive Quercetin-Loaded Supramolecular Hydrogel for Diabetic Wound Healing

Diabetic wound healing remains a significant challenge due to complex pathological mechanisms, including prolonged inflammation, excessive reactive oxygen species (ROS) accumulation, angiogenesis dysfunction, and increased susceptibility to bacterial infection. In this study, we developed a dual ROS/glucose-responsive quercetin-loaded supramolecular hydrogel (GPQ hydrogel) for treating diabetic wounds. The hydrogel was fabricated by incorporating quercetin (QUE) into a guanosine-phenylboronic acid (GP) hydrogel network through dynamic borate ester bonds. Structural characterization revealed the formation of a typical G-quadruplex structure in the GPQ hydrogel. The dual responsiveness to ROS and glucose enabled the controlled release of QUE, effectively addressing the abnormal wound microenvironment in diabetes. <i>In vitro</i> studies demonstrated the excellent antibacterial, antioxidant, anti-inflammatory, and pro-angiogenic properties of the GPQ hydrogel. Furthermore, the <i>in vivo</i> diabetic wound healing study using a full-thickness wound model in streptozotocin-induced diabetic rats showed that the GPQ hydrogel significantly accelerated wound closure, enhanced re-epithelialization and collagen deposition, and promoted angiogenesis compared to the control and GP hydrogel groups. Immunofluorescence analysis confirmed the superior antioxidant and pro-angiogenic effects of the GPQ hydrogel in the wound microenvironment. This study presents a promising multifunctional biomaterial for effectively managing diabetic wounds.