Advanced Multifunctional Hydrogels for Enhanced Wound Healing through Ultra‐Fast Selenol‐S_NAr Chemistry

Abstract Fabrication of versatile hydrogels in a facile and effective manner represents a pivotal challenge in the field of biomaterials. Herein, a novel strategy is presented for preparing on‐demand degradable hydrogels with multilevel responsiveness. By employing selenol‐dichlorotetrazine nucleophilic aromatic substitution (S_NAr) to synthesize hydrogels under mild conditions in a buffer solution, the necessity of additives or posttreatments can be obviated. The nucleophilic and redox reactions between selenol and tetrazine culminate in the formation of three degradable chemical bonds—diselenide, aryl selenide, and dearomatized selenide—in a single, expeditious step. The resultant hydrogel manifests exceptional adaptability to intricate environments in conjunction with self‐healing and on‐demand degradation properties. Furthermore, the resulting material demonstrated light‐triggered antibacterial activity. Animal studies further underscore the potential of integrating metformin into Se‐Tz hydrogels under green light irradiation, as it effectively stimulates angiogenesis and collagen deposition, thereby fostering efficient wound healing. In comparison to previously documented hydrogels, Se‐Tz hydrogels exhibit controlled degradation and drug release, outstanding antibacterial activity, mechanical robustness, and bioactivity, all without the need for costly and intricate preparation procedures. These findings underscore Se‐Tz hydrogels as a safe and effective therapeutic option for diabetic wound dressings.