Silver/copper nanoparticles coated with chitosan and evaluation of their effect on oral pathogens and oral wound healing

Abstract

Oral wounds present unique healing challenges due to microbial exposure, constant movement, and moisture. Metallic nanoparticles such as silver (Ag) and copper (Cu) possess potent antimicrobial and wound-healing properties but are limited by stability and cytotoxicity concerns. This study aimed to develop biocompatible silver/copper nanoparticles coated with chitosan (SILCUCHITNPs) using curcumin as a green reducing agent and evaluate their therapeutic potential in oral wound healing. SILCUCHITNPs were synthesized, characterized by SEM, and tested for cytocompatibility using L929 fibroblast cells. Anti-inflammatory activity was assessed via ELISA in LPS-stimulated RAW 264.7 macrophages. Antimicrobial efficacy was evaluated against Streptococcus mutans, Porphyromonas gingivalis, and Fusobacterium nucleatum using MIC and membrane integrity assays. The nanoparticles were incorporated into calcium alginate hydrogels (SILCUCHITNP-CALALG), and their effects on oral wound healing were investigated in a rat cheek ulcer model via histology and cytokine/growth factor expression profiling. SILCUCHITNPs were spherical with a mean diameter of ~513 nm and showed no cytotoxicity up to 600 µg/mL. They significantly reduced pro-inflammatory cytokines (IL-1β, TNF-α) at higher doses and inhibited oral pathogens in a dose-dependent manner. In vivo, SILCUCHITNP-CALALG hydrogels accelerated mucosal wound closure, reduced inflammation, and enhanced expression of TGF-β, EGF, and bFGF compared to controls. The multifunctional SILCUCHITNP-CALALG hydrogel system combines antimicrobial, anti-inflammatory, and regenerative properties, representing a promising platform for oral wound care and infection control. Future studies are warranted to assess long-term safety and clinical applicability.