Zinc-Based Nanoparticles Reduce the Bacterial Burden and Protect Collagen in a Mouse Cutaneous Wound Model

The persistent threat of multidrug-resistant bacteria, particularly within biofilms, continues to undermine conventional antimicrobial therapies. In this study, we explored the potential of zinc oxide (ZnO) and zinc sulfide (ZnS) nanoparticles (NPs) as alternative strategies to target clinically relevant bacteria such as <i>Staphylococcus aureus</i>, <i>Klebsiella oxytoca</i>, and <i>Pseudomonas aeruginosa</i>. Both NPs exhibited effective antibacterial activity against planktonic forms, with ZnO more potent <i>in vitro</i>. However, ZnS-NPs were more efficacious in disrupting mature biofilms by compromising their metabolic activity. Scanning electron and confocal microscopy revealed that Zn-NP treatment compromised the structural integrity of the biofilms. ZnS-NPs also triggered a marked downregulation of genes associated with <i>P. aeruginosa</i> exopolysaccharide biosynthesis (e.g., <i>pslA</i> and <i>algC</i>), suggesting specific interference in biofilm formation pathways. Topical treatment of skin wound infection in Balb/c mice led to a significant reduction in bacterial burden. Notably, while Zn-NPs did not promote initial wound healing, they inhibited the degradation of collagen by bacteria and/or helped maintain collagen levels in the skin of the mice. These findings demonstrate that Zn-NPs effectively reduce early bacterial burden in mouse skin wounds while preserving cutaneous tissue collagen integrity, establishing their dual therapeutic potential as both antimicrobial and tissue-protective agents in wound management.