Gelatin/starch hydrogel tissue adhesive loaded with EGCG-Zr complex with antibacterial, antioxidant, and immunomodulatory properties for advanced wound healing

Surgical suture techniques are commonly used for hemostasis and wound closure, but they often fail to achieve optimal results, particularly in post-laceration hemostasis and healing. Furthermore, complications such as bacterial infections, oxidative stress, and inflammation often worsen the initial wound, leading to secondary damage. In this study, a novel tissue adhesive was developed by integrating a natural epigallocatechin-3-gallate (EGCG) and zirconium ion (Zr) chelate complex (EGCG-Zr) into a gelatin/starch hydrogel (GDSH). The resulting multifunctional tissue adhesive (EGCG-Zr@GDSH) exhibits excellent injectability, superior adhesion strength compared with commercial protein fiber-based tissue adhesives, and cytocompatibility. The hydrogel enables the sustained release of EGCG and Zr, providing effective antibacterial effects. In vivo histological analysis of an incision wound model revealed that EGCG-Zr@GDSH promotes angiogenesis and collagen deposition, scavenges reactive oxygen species, restores intracellular redox balance, and mitigates oxidative stress-induced cellular damage. Moreover, it regulates M1 macrophage polarization, thereby reducing the secretion of proinflammatory cytokines and alleviating inflammation. This hydrogel possesses antioxidant and immunomodulatory properties, indicating its application potential as a tissue adhesive and highlighting the importance of immune regulation in tissue repair and regeneration.