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

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.

High throughput image cytometry micronucleus assay to investigate the presence or absence of mutagenic effects of cold physical plasma

“…Yet, clinical plasma are usually applied repetitively, resulting in higher total exposure times. Testing for such conditions in vivo, mice with ear wounds treated for 14 consecutive days with this plasma jet did not display any sign of cancer formation or mutagenic action one year later [Schmidt et al, 2017c]. Contrasting our in vitro results, another study using a dielectric barrier discharge working in atmospheric air, strong micronuclei formation was observed in TG98 cancer cells [Kaushik et al, 2012].…”

“…In human volunteers, plasma treatment time was up to 30 sec/cm 2 of skin, which lies in the recommended range of 30-60 sec/cm 2 [Bekeschus et al, 2016b]. Testing for such conditions in vivo, mice with ear wounds treated for 14 consecutive days with this plasma jet did not display any sign of cancer formation or mutagenic action one year later [Schmidt et al, 2017c]. Moreover, it needs to be considered that tissue contains much more cells and biomolecules absorbing the energy compared with only one million cells per sample used in this in vitro study.…”

A Comparison of Floating-Electrode DBD and kINPen Jet: Plasma Parameters to Achieve Similar Growth Reduction in Colon Cancer Cells Under Standardized Conditions

“…Treatment with the genotoxically-safe [64][65][66] atmospheric pressure argon plasma jet kINPen 11 (similar in construction to the kINPen MED that has received accreditation as medical device in Germany; neoplas control, Germany) operated at a feed gas flux of three standard liters per minute (SLPM) of Argon gas (Air Liquide, France) was performed as described previously [67]. It is a DBD-like jet, with a central pin electrode shielded against an outer electrode by a dielectric, powered by 2-6 kV at 1 MHz.…”

The Canady Helios Cold Plasma Scalpel Significantly Decreases Viability in Malignant Solid Tumor Cells in a Dose-Dependent Manner

“…CAP is an emerging technology that uses ionized gas to produce a plasma beam which has numerous applications in various fields, including dentistry, wound healing, surface decontamination, viral inhibition, and cancer treatment [11][12][13][14][15][16]. CAP can be used to treat the margins following tumor removal, and in doing so has the potential to remove residual cancer cells and prevent recurrence.…”