Background: It is widely acknowledged that pathogenic germs delay wound healing to some extent. To explore factors influencing the wound healing process, the current study was conducted to evaluate the antibacterial effect of topical application of copper sulfide nanoparticles (CuS NPs) in vitro and on infected wound healing process in the rat model. Materials and Methods: In this study, the morphology and size of CuS NPs were detected. Staphylococcus aureus and Escherichia coli were used so that the antibacterial ability of CuS NPs could be evaluated better. In addition, a 2-cm circular full-thickness wound infected with a solution of 10⁷ colony forming units (CFU) Staphylococcus aureus was created on the back of each rat. The rats were divided into four groups including the control group, the 100 mcg/mL CuS NPs group, the 250 mcg/mL CuS NPs group, and the 500 mcg/mL CuS NPs group. Tissue bacterial count and histologic assessment were evaluated. Results: The results indicated that CuS NPs had antibacterial activity against Staphylococcus aureus and Escherichia coli. Moreover, they could decrease the incidence of bacterial colonization and promote wound healing through re-epithelialization and collagen deposition. Furthermore, CuS NPs could maintain Cu²⁺ continuous release and inhibit the viability of Staphylococcus aureus through lipid peroxidation. Conclusions: This study found that CuS NPs have fine antibacterial properties, and particularly, the 500 mcg/mL CuS NPs had better effects, without increase of side effects. They could promote infected wound healing, the prospective clinical application of which was further confirmed in the treatment of wound infection.

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