Antimicrobial Effect of Plasma-Treated Liquids on Skin and Oral Biofilms: A Systematic Review of In Vitro Studies

Featured Application: This review highlights the potential of indirect cold atmospheric plasma as an antimicrobial approach against oral and skin biofilms and provides a framework for the standardization of experimental protocols and the translation of plasma-based technologies into clinical practice. This systematic review aimed to evaluate the effectiveness of indirect cold atmospheric plasma (CAP) in disrupting oral and skin microbial biofilms and to investigate whether the reported effects are mainly attributable to acidic pH, plasma-activated liquids, or specific devices and treatment settings. The review followed PRISMA guidelines and was registered on the Open Science Framework. A comprehensive literature search was conducted across major electronic databases. Studies evaluating indirect CAP on in vitro oral and skin microbial biofilms were included. Comparisons were made with untreated controls, non-activated liquids, and conventional antimicrobials. Outcomes were evaluated based on reductions in biofilm viability or biomass using quantitative assays (e.g., CFU, XTT, and Crystal Violet). Thirteen in vitro studies were included. CFU-based outcomes were reported in 11 of 13 studies (84.61%), and all of these studies showed reductions exceeding 5–6 log under specific conditions. Antimicrobial efficacy varied according to exposure time, microbial species, plasma parameters, and treatment settings, while physicochemical analyses indicated that acidic conditions and plasma-activated liquids play a key role. Indirect CAP appears to be a promising non-invasive antimicrobial strategy for managing oral and skin biofilms. However, variability among devices and settings, together with the absence of clinical data, underscores the need for further standardized studies and clinical investigations.