Antioxidant Self-Healing Hydrogel Containing Myricetin for Full-Thickness Wound Repair

The accumulation of reactive oxygen species (ROS) in wounds impairs tissue regeneration and functional reconstruction, hindering full-thickness wound repair. In this study, we developed an antioxidant self-healing hydrogel incorporating myricetin, a natural compound, to effectively scavenge ROS over an extended period, facilitating full-thickness wound repair. We synthesized an α-aminophosphonate polymer containing phenylboronic acid and antioxidant groups via the Kabachnik–Fields reaction by modifying a polycondensate with phosphite groups. This antioxidant polymer effectively binds myricetin through the borate ester formation. The polymer–myricetin complex rapidly cross-links with poly(vinyl alcohol) to form a hydrogel via borate esters. The resulting hydrogel demonstrates self-healing properties, shape adaptability, and biocompatibility. The incorporated myricetin enhances the hydrogel’s antioxidant capacity and is released in a controlled manner under acidic and oxidative conditions. In animal studies, the myricetin-loaded self-healing hydrogel substantially accelerated wound healing and achieved full-thickness tissue regeneration, outperforming a commercial clinical dressing. This study underscores the potential of integrating natural products with self-healing hydrogels for full-thickness wound repair and provides insights into the application of multicomponent reactions in biomacromolecule and biomaterial development.