OICC Press Journal of Nanostructure in Chemistry 2193-8865 15 4 2025 08 31 In Situ Silver Nanoparticle–Hyaluronic Acid Hydrogel for Enhanced Wound Healing 10.57647/jnsc.2025.1504.16 EN Yang Li Department of Plastic and Reconstructive Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, China; Department of Plastic Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong, 250013, China https://orcid.org/0000-0002-4109-1127 Juan Xie Department of Plastic and Reconstructive Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, China Dongsheng Cao Department of Plastic and Reconstructive Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, China Journal Article 2025 08 31 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.