Non-Thermal Atmospheric Pressure Argon-Sourced Plasma Flux Promotes Wound Healing of Burn Wounds and Burn Wounds with Infection in Mice through the Anti-Inflammatory Macrophages

Abstract

Plasma medicine is the utilization of gas ionization that might be beneficial for the treatment of burn wounds, a healthcare problem with a significant mortality rate. Due to a lack of information on the impact of plasma flux in immune cells and a high prevalence of bacterial infection in burn wounds, non-thermal argon-based plasma flux was tested on macrophages (RAW246.7) and in mouse models of burn wounds with or without Staphylococcus aureus infection. Accordingly, plasma flux enhanced reactive oxygen species (ROS), using dihydroethidium assay, and decreased abundance of NF-κB-p65 (Western blot analysis) in non-stimulating macrophages. In parallel, plasma flux upregulated IL-10 gene expression (an anti-inflammatory cytokine) in lipopolysaccharide (LPS)-induced inflammatory macrophages, while downregulating the pro-inflammatory cytokines (IL-1β and IL-6). Additionally, plasma flux improved the migratory function of fibroblasts (L929) (fibroblast scratch assay) but not fibroblast proliferation. Moreover, once daily plasma flux administration for 7 days promoted the healing process in burn wounds with or without infection (wound area and wound rank score). Additionally, plasma flux reduced tissue cytokines (TNF-α and IL-6) in burn wounds with infection and promoted collagen in burn wounds without infection. In conclusion, plasma flux induced anti-inflammatory macrophages and promoted the burn-wound healing process partly through the decrease in macrophage NF-κB. Hence, plasma flux treatment should be tested in patients with burn wounds.