Non-Thermal Atmospheric Pressure Plasma promotes healing of excisional skin wounds in caloric restricted rats

Therapeutic strategies to accelerate healing remain crucial, particularly during caloric restriction (CR), as nutritional deficiency can delay healing. Non-Thermal Atmospheric Pressure Plasma (AP) has been highlighted as appropriate therapy for tissue healing, showing pioneering results associated with 30% CR. Herein, 40 male Wistar rats with 30% CR and excisional lesions, created using 1.5 cm diameter dermatological punch, were divided into sham (lesions treated with the equipment turned off) and AP (topical and daily treatment with AP for 60s) groups. Animals were euthanized on 2nd, 7th, 14th and 21st days post-injury, and skin/lesion/scar samples were harvested for analyses: histomorphometric (inflammatory infiltrate, blood vessels, fibroblasts, collagen and hair follicles), biochemical [(myeloperoxidase–neutrophil, N-acetylglucosaminidase–macrophage), oxidative stress (nitric oxide, dichlorofluorescein, carbonyl, sulfhydryl, superoxide dismutase, and glutathione)], molecular (interleukin [IL]-1β, IL-10, transforming growth factor [TGF]-β1, vascular epithelial growth factor [VEGF], collagen III and I), and re-epithelialization (wound healing rate). The AP group showed better results than the sham group, with elevated levels of inflammatory infiltrate, IL-1β, and IL-10. AP treatment modulated oxidative stress and enhanced TGF-β1 and VEGF levels, presenting increased hair follicles, fibroblasts, and collagen I and III, promoting wound re-epithelialization. Therefore, AP could be a promising therapy for wound healing, even during 30% CR.