Low‐intensity cold atmospheric plasma reduces wrinkles on photoaged skin through hormetic induction of extracellular matrix protein expression in dermal fibroblasts

Background: Recent evidence indicates that cold atmospheric plasma (CAP) can upregulate the production of extracellular matrix (ECM) proteins in dermal fibroblasts and enhance transdermal drug delivery when applied at a low intensity. Objectives: The aim of this study was to evaluate the effect of low-intensity CAP (LICAP) on photoaging-induced wrinkles in an animal model and the expression profiles of ECM proteins in human dermal fibroblasts. Methods: Each group was subjected to photoaging induction and allocated to therapy (LICAP, topical polylactic acid (PLA), or both). The wrinkles were evaluated via visual inspection, quantitative analysis, and histology. The expression of collagen I/III and fibronectin was assessed using reverse transcription-quantitative polymerase chain reaction, western blot analysis, and immunofluorescence. The amount of aqueous reactive species produced by LICAP using helium and argon gas was also measured. Results: Wrinkles significantly decreased in all treatment groups compared to those in the untreated control. The differences remained significant for at least 4 weeks. Dermal collagen density increased following LICAP and PLA application. LICAP demonstrated a hormetic effect on ECM protein expression in human dermal fibroblasts. The production of reactive species increased, showing a biphasic pattern, with an initial linear phase and a slow saturation phase. The initial linearity was sustained for a longer time in the helium plasma (similar to 60 s) than in the argon plasma (similar to 15 s). Conclusion: LICAP appears to be a novel treatment option for wrinkles on the photodamaged skin. This treatment effect seems to be related to its hormetic effect on dermal ECM production.