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) alongside graphene quantum dots (GQDs) incorporation in 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 optimised 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.