Research Article: Side effects by oral application of atmospheric pressure plasma on the mucosa in mice

Date Published: April 9, 2019

Publisher: Public Library of Science

Author(s): Lukasz Jablonowski, Thomas Kocher, Axel Schindler, Karolina Müller, Frank Dombrowski, Thomas von Woedtke, Thomas Arnold, Antje Lehmann, Stefan Rupf, Matthias Evert, Katja Evert, Peter Eickholz.


Cold atmospheric pressure plasma (CAP) has been investigated with promising results for peri-implant diseases treatment. However, prior to in-vivo applications of CAP sources in humans, short-term harmful mucosal damage or other unwanted side effects have to be reviewed. 180 male mice (B6C3F1) were divided into twelve treatment groups (n = 15). The right buccal cheek mucosa was treated with CAP. The first and second group each received continuous 10 sec irradiation with 2 different plasma sources (kINPen09, PS-MWM). The third group was treated with the kINPen09 for one minute. Control groups were treated with a corresponding dose of ultraviolet light for 8 seconds or 48 seconds and the other one was left untreated. The animals were weighed before and after treatment. The animals were sacrificed one day or one week after exposure. Stained tissue samples were histologically examined for tissue damage independently by two experienced pathologists. One day after CAP treatment histological analysis showed focal mucosal erosion with superficial ulceration and necrosis accompanied by a mild inflammatory reaction. One week after CAP treatment, the mucosal defects were completely re-epithelialized, associated with remnants of granulation tissue in the stroma irrespective of treatment duration. Furthermore, no cytological atypia was found and no severe weight loss occurred. The control groups did not show any alterations at all. CAP treatment led to a superficial mucosal damage that healed within few days. Nonetheless, further long-term experiments are necessary to exclude undesirable side effects after longer observation time. Particularly, potential carcinogenic effects must be ruled out prior to the application of CAP treatment in daily dental practice.

Partial Text

Potential dental therapeutic applications of cold atmospheric pressure plasma (CAP) are manifold [1,2], one of the most promising properties is its antimicrobial activity [3–7]. Another property of plasma is its ability to modify a hydrophobic surface into a superhydrophilic one, which stabilizes clots and supports early wound healing of implants [8–11]. Thus, CAP may offer a novel approach for the treatment of peri-implant diseases [6]. Recently, cold atmospheric-pressure plasma devices have been developed, which have a temperature range between 40°C and 50°C in the interaction zone.

In conclusion, the CAP-treatment is well tolerated in mice in short-term experiments. Further investigations are required to answer the most important question: How safe is atmospheric pressure plasma in long-term experiments? Is there a carcinogenic risk, in particular in cases of repetitive applications over a prolonged period or in subjects with additional risk factors for oral cancer such as smokers? To answer these questions, long-term experiments are necessary. Especially, a late manifesting co-carcinogenic effect of the intra-oral treatment must be ruled out before treatment with plasma can be established as an alternative therapy in dentistry.




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