An Intelligent Hydrogel Platform with Triple-Triggered On-Demand Release for Accelerating Diabetic Wound Healing

The hydrogel platform with intelligent drug delivery system possesses great potential in the treatment of diabetic wounds. Nevertheless, the intelligent elimination of reactive oxygen species (ROS) remains a formidable challenge in facilitating diabetic wound healing. Herein, a hydrogel platform with triple-triggered on-demand release is constructed to intelligently scavenge ROS and modulate the wound microenvironment to accelerate diabetic wound healing through the release of antioxidative factors. Specifically, the gelatin (Gel) is modified with phenylboronic acid (PBA) to obtain a glucose-sensitive Gel derivative (Gel-BA), which is mixed with oxidized dextran (ODex) and the strong antioxidant myricetin (MY) to swiftly generate a hydrogel platform (OGM). Significantly, the smart release of MY from the hybrid hydrogel under inflammatory conditions intelligently eliminates ROS, effectively alleviating oxidative stress and promoting angiogenic reprogramming of the wound immune microenvironments by activating the Nrf2 pathway. In summary, in vitro and in vivo studies reveal that the OGM hydrogel platform significantly promotes cell proliferation, migration, and tube formation and greatly accelerates diabetic wound healing, offering a local-specific triple-response drug release strategy for the treatment of diabetic wound management.