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. In vitro studies demonstrated the excellent antibacterial, antioxidant, anti-inflammatory, and pro-angiogenic properties of the GPQ hydrogel. Furthermore, the in vivo 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.