Gelatin-carboxymethyl cellulose hydrogels regulated by interactions between epigallocatechin-3-gallate-arginine and copper(II): Structure-property-bioactivity relationships.
Gelatin (Gel) and carboxymethyl cellulose (CMC) provide complementary reactive groups for EDC/NHS-mediated covalent crosslinking and hydrogen bonding. Here, a hydrated, self-supporting Gel-CMC hydrogel (CCE@Cu) incorporating a thermally treated epigallocatechin-3-gallate-arginine product (EA) and Cu2+ was developed as a responsive wound dressing. EA content and Cu2+ feed were systematically varied to regulate reversible interactions and tensile behavior, while pH and temperature were examined as determinants of swelling, mass loss, and release. Spectroscopic analyses confirmed formation of an EA product distinct from the physical mixture and its integration into the Gel-CMC matrix. SEM/EDS revealed an interconnected porous architecture with dispersed Cu throughout the network. The optimized hydrogel exhibited elastic-dominant behavior, rapidly recovered its modulus after repeated disruption at 200% strain, and achieved 432% elongation at break. Elevated temperature and alkaline pH promoted gelatin-chain relaxation and ionization of CMC and phenolic groups, thereby enhancing swelling, mass loss, and release of UV-absorbing EA/EGCG-derived species. CCE@Cu scavenged approximately 73% of DPPH radicals, produced inhibition zones against Staphylococcus aureus and Escherichia coli, maintained approximately 99-100% L929 cell viability, and induced less than 5% hemolysis. In a proof-of-concept diabetic mouse model, CCE@Cu achieved 96.27% wound closure by day 14, accompanied by increased regenerated-tissue thickness and collagen deposition and reduced inflammatory infiltration. Collectively, these results establish composition-dependent relationships among hydrogel network structure, mechanical resilience, stimulus-responsive transport, and biological performance and support CCE@Cu as a promising responsive dressing for diabetic wound repair, warranting further evaluation of its longer-term safety and efficacy.