From Molecular Architecture to Bioactivity: Unlocking the Potential of Chitosan-Ag ₃ PO ₄ Hybrid Hydrogels

This study reports the formation and characterization of chitosan hydrogels cross-linked with Ag 3 PO 4 nanoparticles, developed through electrostatic and coordination–driven interactions. Gelation occurred above 0.5 wt % Ag 3 PO 4 at pH 6, where protonated amino groups interacted with negatively charged Ag–O clusters, as confirmed by zeta potential, X-ray photoelectron spectroscopy, and density functional theory analyses. Rheological tests revealed storage moduli of up to 240 Pa, indicating strong elastic networks, while scanning electron microscopy images showed a transition from lamellar to compact porous architectures. The composites exhibited enhanced stability, remaining intact for over 100 days in aqueous media. ICP–OES measurements showed controlled Ag + release from 0.5 to 20 ppm depending on nanoparticle content. Reactive oxygen species scavenger assays demonstrated 1 O 2 as the main oxidative species driving photocatalytic and antimicrobial activity. The hydrogels inhibited Pseudomonas aeruginosa and MRSA, achieving normalized inhibition halo widths above 0.8 mm, and displayed strong antiviral action against bacteriophage MS2. Cytotoxicity assays with HaCaT cells indicated that only the 0.5 wt % formulation maintained over 90% viability, balancing antimicrobial efficacy and biocompatibility. These results establish Ag 3 PO 4 -chitosan hydrogels as multifunctional biomaterials with promising potential for antimicrobial coatings, wound dressings, and skin regeneration applications.