Synergistic silver nanoparticle-graphene quantum dot composites in silk fibroin/lathyrus protein-oxidized alginate hydrogels for accelerated diabetic wound healing

Abstract

Diabetic wounds require an advanced wound care solution for faster recovery and reduced complications. In this direction, an injectable, self-healing hydrogel (HG) platform based on dynamic Schiff-base crosslinking between oxidized alginate (oAlg) and natural proteins (silk fibroin or Lathyrus sativus-derived plant protein) is developed for the treatment of infected diabetic wounds. The mild one-pot in situ fabrication enables the reduction of silver ions to silver nanoparticles (hereafter denoted as Ag) and the incorporation of graphene quantum dots (GQDs) into the HG matrix. This creates a synergistic antibacterial composite uniformly distributed within the HG network. The Ag–GQD combination that exhibits potent bactericidal and anti-biofilm activity against both Gram-negative (Escherichia coli) and Gram-positive (Micrococcus luteus) strains—comparable or superior to antibiotic, ciprofloxacin—through multi-modal mechanisms involving membrane disruption, reactive oxygen species generation, and impaired extracellular polymeric substance assembly. Both HGs demonstrate excellent hemocompatibility (<5% hemolysis), cytocompatibility (>80% cell viability), and shear-thinning injectability. In a streptozotocin-induced type-1 diabetic rat model of full-thickness infected wounds, the optimized silk fibroin-based Ag + GQD-loaded HG achieves complete re-epithelialization within nine days, with minimal inflammation, no scarring, and near-total bacterial eradication—significantly outperforming controls. This biocompatible, protein-reinforced oAlg HG formulation, leveraging sustainable nature-derived components and synergistic nanomaterial action, offers a promising antibiotic-free dressing to combat resistant infections and accelerate healing in chronic diabetic wounds.