Safety implications of plasma-induced effects in living cells - A review of in vitro and in vivo findings

Cold atmospheric plasma is a versatile new tool in the biomedical field with applications ranging from disinfection, wound healing and tissue regeneration to blood coagulation, and cancer treatment. Along with improved insights into the underlying physical, chemical and biological principles, plasma medicine has also made important advances in the introduction into the clinic. However, in the absence of a standard plasma 'dose' definition, the diversity of the field poses certain difficulties in terms of comparability of plasma devices, treatment parameters and resulting biological effects, particularly with regards to the question of what constitutes a safe plasma application. Data from various in vitro cytotoxic and genotoxic studies along with in vivo findings from animal and human trials are reviewed to provide an overview of the current state of knowledge on the safety of plasma for biological applications. Treatment parameters employed in clinical studies were well tolerated but intense treatment conditions can also induce tissue damage or genotoxicity. There is a need identified to establish both guidelines and safety limits that ensure an absence of (long-term) side effects and to define treatments as safe for applications, where cell stimulation is desired, e.g. in wound healing, or those aimed at inducing cell death in the treatment of cancer.