Zinc-phenolic coordination-driven gelatin hydrogel networks with enhanced biological properties for tissue regeneration

Abstract

Tissue regeneration is a complex biological process requiring the coordinated regulation of antibacterial, antioxidant, adhesive, and angiogenic responses, which demands multifunctional biomaterials capable of addressing multiple healing pathways simultaneously. In this study, a gelatin-based multifunctional hydrogel is developed by first conjugating tannic acid onto gelatin chains to form a gelatin–tannic acid polymer, followed by zinc-ion-mediated crosslinking to generate a hydrogel network. Gel formation is primarily driven by metal–phenolic coordination between zinc ions and tannic acid, while additional interactions between tannic acid and gelatin contribute to network stability. The hydrogel is fabricated through a single step mixing process, enabling rapid gelation within approximately 10 seconds. The resulting hydrogel exhibits a storage modulus of approximately 300 Pa and a uniform porous microstructure, providing sufficient structural integrity. Strong wet tissue adhesion up to 14 kPa is achieved, together with tannic-acid-derived antioxidant activity. Zinc incorporation further imparts effective antibacterial performance against both Gram-positive and Gram-negative bacteria and significantly enhances endothelial angiogenic activity through sustained ion release. In vivo full-thickness wound studies confirm accelerated cutaneous tissue regeneration. This study establishes a coordination-driven strategy for engineering gelatin-based hydrogels with tunable structure and multifunctional performance.