Short-peptide based supramolecular nanocomposite hydrogels for the disruption of polymicrobial biofilms and accelerated infected wound healing

The escalating prevalence of drug-resistant microbes coupled with their persistence in mono- and polymicrobial biofilms impose a critical healthcare challenge. Metal nanoparticles, particularly silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs), offer potent antimicrobial activity but face limitations due to their complex synthetic protocols, reliance on external reducing agents and surfactants, resulting compromised biocompatibility and poor <i>in vivo</i> outcomes. Herein, we present a facile, biocompatible approach for synthesizing antimicrobial supramolecular nanocomposite hydrogels (ASNH) <i>via</i> a one-pot, aqueous process that enables <i>in situ</i> growth of AgNPs and AuNPs through supramolecular interactions with short peptides. Utilizing sunlight photoirradiation, these hydrogels eliminate external reducing agents while serving as stabilizers for nanoparticle formation. The metallohydrogels exhibit rapid and broad-spectrum antimicrobial activity, against multidrug resistant bacteria and fungi. In addition to disrupting single species biofilms, the optimal hydrogels significantly eradicate polymicrobial biofilms formed by MRSA and <i>Candida albicans</i>. The hydrogels achieve ≥1.5-log reduction in microbial viability, outperforming last resort antibiotics and commercial silver-based ointments. <i>In vivo</i> studies demonstrate accelerated wound healing by reducing bacterial burden and mitigating inflammatory responses, while enhancing neovascularization, granulation, fibroblast proliferation, collagen deposition and epithelialization. The mild, economical synthesis and robust antimicrobial efficacy of these peptide-based metallohydrogels underscore their clinical potential as next-generation biomaterials for polymicrobial biofilm-associated infections.