pH-Responsive Smart Hydrogel Dressing for Controlled Antimicrobial Therapy and Accelerated Wound Healing

Abstract

Bacterial wound infections pose a major clinical challenge, often causing delayed healing, recurrent infections, and increased antibiotic resistance. Conventional antibiotics are largely ineffective against biofilm-associated bacteria, underscoring the need for advanced antimicrobial approaches. Silver nanoparticles (AgNPs) exhibit potent, broad-spectrum antibacterial activity, but their clinical use is restricted by uncontrolled ion release and cytotoxicity. Here, we present a pH-responsive hydrogel composed of hyaluronic acid (HA) and acrylamide (AM), cross-linked with N, N′-methylenebisacrylamide and incorporating well-dispersed AgNPs, as a multifunctional wound dressing. The hydrogel is designed to respond to infection-related pH changes, enabling controlled AgNPs release under alkaline conditions while retaining silver at physiological skin pH to reduce toxicity. HA stabilizes AgNPs and enhances swelling but also contributes to hydration, cell adhesion, and wound regeneration. Notably, hair regrowth was observed, suggesting potential benefits in follicle repair. The hydrogel demonstrates marked pH-dependent swelling, allowing programmable AgNPs release matched to infection severity. In vitro studies confirmed strong antibacterial activity against Gram-positive (Staphylococcus aureus, methicillin-resistant Staphylococcus aureus) and Gram-negative (Escherichia coli) strains, with effective biofilm suppression. Biocompatibility assays using human colorectal adenocarcinoma cells (Caco-2) and mouse fibroblast cells (L929) validated cytocompatibility. This facile and scalable platform offers a promising therapeutic strategy for infected wounds.