Resveratrol-Engineered Modified Chitosan-PVP-AgNP Composite Hydrogel Patch: A Potential Antibacterial and Antioxidant Biomaterial for Infected Wound Healing.

Abstract

Chronic infected wounds remain a significant clinical challenge due to persistent microbial colonization, excessive reactive oxygen species (ROS) generation, and impaired tissue regeneration. These pathological conditions disrupt key healing processes, such as re-epithelialization, angiogenesis, and extracellular matrix (ECM) remodeling, necessitating advanced wound dressings capable of simultaneously addressing infection and oxidative stress. In this work, a multifunctional hydrogel patch was developed by chemically modifying chitosan with N-acetylsulfonyl chloride (CS-NASC) and forming a cross-linked network with polyvinylpyrrolidone (PVP), followed by the incorporation of silver nanoparticles (AgNPs) and resveratrol (RSV). FTIR spectroscopy confirmed successful chemical modification and intermolecular interactions within the hydrogel matrix. The hydrogel exhibited pH-responsive swelling behavior, achieving a high swelling ratio of approximately 1500% at pH 7.4, indicating excellent fluid absorption capacity under wound-relevant conditions. Scanning electron microscopy revealed a porous architecture with an average pore size of ∼151 μm, favorable for exudate absorption and nutrient transport. The developed hydrogel demonstrated strong antibacterial activity, with zones of inhibition of 18.0 ± 0.1 mm against Staphylococcus aureus and 20.0 ± 0.1 mm against Escherichia coli, attributed to the synergistic antimicrobial effects of NASC and AgNPs. Additionally, the presence of RSV imparted significant antioxidant activity, with 65-85% DPPH radical scavenging efficiency. Cytocompatibility evaluation using the MTT assay confirmed excellent cell viability (>95% viability), while rheological analysis indicated stable viscoelastic behavior with G' > G″, ensuring structural integrity suitable for wound application. In vivo evaluation using a coinfected wound model demonstrated that the hydrogel patch significantly enhanced wound healing, achieving 91.96% wound contraction within 14 days, along with a marked reduction in bacterial load and increased collagen deposition (0.6643 μg/mg hydroxyproline) compared to control groups. Histopathological analysis further confirmed improved tissue regeneration, including enhanced re-epithelialization and collagen organization. Overall, the CS-NASC/AgNPs/RSV/PVP hydrogel patch represents a promising multifunctional dressing for the effective management of infected wounds.