Carrageenan/Poly(vinyl alcohol) Double-Network Hydrogel Incorporating Antioxidative Copper-l-Cysteine Nanoparticles for Infected Wound Treatment

Effective treatment of infected wounds requires simultaneous eradication of invading pathogens and scavenging of excess reactive oxygen species (ROS). Herein, we fabricated a multifunctional hydrogel dressing (denoted as PVA/CG/Cu-Cys) by hydrogen-bond cross-linking poly(vinyl alcohol) with ι-carrageenan-Ca2+ helices to generate a double network that was subsequently loaded with copper-l-cysteine nanoparticles. The reversible hydrogen-bonded interpenetrating network provided adequate swelling, moldability, mechanical strength, and tissue adhesion. The Cu-Cys nanoparticles endowed the hydrogel with broad-spectrum antioxidant activity, achieving over 60% scavenging efficiency against a range of reactive oxygen (H2O2, •OH, and •O2–) and nitrogen species (DPPH• and ABTS•+). Controlled release of Cu2+ eradicated 50.84 ± 8.21% of S. aureus biofilms and inhibited both E. coli and S. aureus. At the acidic pH of infected wound area (5.6), the hydrogel released only 56.5 ± 3.0% of total Cu2+ in 24 h, significantly less than free Cu-Cys (81.1 ± 2.7%, p = 0.0025), thereby reducing cytotoxicity and maintaining >80% cell viability. The dressing promoted in vitro cell migration and accelerated closure of infected full-thickness wounds in vivo. These results indicate that PVA/CG/Cu-Cys is a readily fabricated, clinically translatable dressing for the management of bacterially infected wounds.