One Year Follow-Up Risk Assessment in SKH-1 Mice and Wounds Treated with an Argon Plasma Jet.

Anke Schmidt,Thomas Woedtke,Sander Bekeschus,Brigitte Vollmar,Jan Stenzel,Stefan Polei,Tobias Lindner

doi:10.3390/ijms18040868

Abstract

Multiple evidence in animal models and in humans suggest a beneficial role of cold physical plasma in wound treatment. Yet, risk assessment studies are important to further foster therapeutic advancement and acceptance of cold plasma in clinics. Accordingly, we investigated the long-term side effects of repetitive plasma treatment over 14 consecutive days in a rodent full-thickness ear wound model. Subsequently, animals were housed for 350 days and sacrificed thereafter. In blood, systemic changes of the pro-inflammatory cytokines interleukin 1β and tumor necrosis factor α were absent. Similarly, tumor marker levels of α-fetoprotein and calcitonin remained unchanged. Using quantitative PCR, the expression levels of several cytokines and tumor markers in liver, lung, and skin were found to be similar in the control and treatment group as well. Likewise, histological and immunohistochemical analysis failed to detect abnormal morphological changes and the presence of tumor markers such as carcinoembryonic antigen, α-fetoprotein, or the neighbor of Punc 11. Absence of neoplastic lesions was confirmed by non-invasive imaging methods such as anatomical magnetic resonance imaging and positron emission tomography-computed tomography. Our results suggest that the beneficial effects of cold plasma in wound healing come without apparent side effects including tumor formation or chronic inflammation.

Highlights

Cold atmospheric pressure plasma has emerged as a promising tool for biomedical and clinical applications [1]
The data provided in these studies demonstrated the absence of mutagenic or genotoxic effects in plasma-treated cells or in a hen’s egg test model for micronuclei induction (HET-MN), suggesting that a clinical application of the argon plasma jet does not pose mutagenic risks
Using quantitative PCR, Enzyme-linked immunosorbent assay (ELISA) measurements, and immunohistochemical analysis of several tumor markers, we investigated primary tumor formation or metastasis of malignant tumors

Summary

Introduction

Cold atmospheric pressure plasma has emerged as a promising tool for biomedical and clinical applications [1]. The data provided in these studies demonstrated the absence of mutagenic or genotoxic effects in plasma-treated cells or in a hen’s egg test model for micronuclei induction (HET-MN), suggesting that a clinical application of the argon plasma jet does not pose mutagenic risks. This is confirmed by a clinical long-term observation of laser skin lesions which were treated by cold atmospheric plasma [33,34]. Systematic in vivo studies investigating any malignant side effects of plasma have not carried out to date

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