Zinc Peroxide-Mediated In Situ Forming Hydrogels for Endogenous Tissue Regeneration

Bioactive hydrogels have garnered considerable attention for endogenous tissue regeneration owing to their affordability, minimal regulatory barriers, and ability to harness the body's intrinsic healing potential. Recently, inorganic-ion-releasing hydrogels have been developed as bioactive matrices, promoting wound healing and tissue repair through external cellular stimulation. Among various therapeutic inorganic ions, zinc ions (Zn²⁺), in particular, play essential roles in wound healing by modulating cell proliferation and angiogenesis and facilitating tissue remodeling. Numerous strategies have been developed to fabricate Zn²⁺-releasing biomaterials; however, these methods often encounter challenges, including complex fabrication processes, rapid ion release, and limited mechanical stability. To address these challenges, we developed a novel Zn²⁺-releasing bioactive hydrogel (Zn-Gel) as a bioactive matrix that supported wound healing via a zinc peroxide (ZnO₂)-mediated cross-linking reaction. Zn-Gel was fabricated by combining thiolated gelatin with ZnO₂ solutions, forming a hydrogel with controllable Zn²⁺ release kinetics that depended on ZnO₂ concentration and enabled sustained release of Zn²⁺ for up to 14 d. Zn-Gel demonstrated excellent cytocompatibility and tissue compatibility in both in vitro and in vivo studies. Interestingly, Zn-Gel accelerated wound healing by promoting cell proliferation, blood vessel formation, hair follicle formation, and collagen deposition. Therefore, Zn-Gel holds great potential as an advanced bioactive material for wound healing and tissue regeneration.