In Situ Silver Nanoparticle–Hyaluronic Acid Hydrogel for Enhanced Wound Healing

A multifunctional hyaluronic acid (HA) hydrogel incorporating in situ–synthesized silver nanoparticles (AgNPs) was developed. This method generated uniformly distributed spherical AgNPs (~22 nm) within the HA matrix without the need for toxic reducing agents, resulting in a porous, biodegradable nanocomposite with a high surface area (121.7 m²/g). The hydrogel demonstrated exceptional swelling capacity (>1200%), sustained silver ion release, and potent antibacterial activity against S. aureus (MIC 8 µg/mL) and P. aeruginosa (MIC 4 µg/mL) while maintaining >95% viability in human dermal fibroblasts, confirming a favorable therapeutic window. In a full-thickness rat wound model, the HA–AgNP hydrogel achieved >98% wound closure by day 14, accompanied by complete re-epithelialization, dense collagen deposition, and neovascularization, markedly outperforming HA-only and untreated controls. These findings are consistent with recent research trends that emphasize eco-friendly AgNP synthesis and HA-based biomaterials to combine infection control with pro-regenerative effects, minimizing cytotoxicity and supporting rapid, high-quality tissue repair. This work thus presents a clinically translatable, scalable nanoplatform that unites antimicrobial efficacy with regenerative capacity for the treatment of infected and chronic wounds. The hydrogel's performance is driven by a synergistic mechanism where the controlled release of AgNPs provides potent, localized antimicrobial action while the HA matrix creates a pro-regenerative microenvironment, thereby minimizing cytotoxicity and supporting high-quality tissue repair.