# Cold Atmospheric Pressure Plasma in Wound Healing and Cancer Treatment
## 4 Properties of CAP Stimulate Tissue Regeneration but May also Induce Cell Death  
At first glance, it seems contradictory to use CAP on the one hand for wound healing to stimulate tissue regeneration, and on the other hand, for cancer therapy to inhibit cell proliferation and induce cell death. How can one application exhibit such opposite properties? As [PERSON] already stated in his Third Defense in 1538, \"Sola dosis facit venenum\"--only the dose makes the poison. This also holds true for CAP--low doses can be beneficial, while high doses can be destructive. Hence, when using CAP for wound treatment, \"overdosing\" should be avoided to prevent adverse effects. Likewise, \"under-dosing\" may not have the desired lethal effect on cancer cells when applying CAP for cancer therapy. Due to the vast range of different plasma devices and operating parameters being used in plasma medicine, the term \"dose\" is not well defined and somewhat controversial. Therefore, identifying the optimal treatment modalities for the different applications of CAP is one of the main challenges that need to be solved in future clinical trials. To find the optimal treatment modalities for each application and clinical setting, it helps to understand the molecular mechanisms of action of CAP. Although progress has been made for understanding the underlying mechanisms of CAP in wound healing and cancer treatment, much still needs to be explored. In this section, the current understanding of the molecular mechanisms will be discussed briefly. As this is a very complex field and many aspects need to be considered, this overview is not intended to be comprehensive and may not be exhaustive and complete. Instead, it is meant to provide a basic understanding of how CAP may have stimulating or inhibiting properties (Figure 1). The biological efficacy of CAP is mostly attributed to chemical components (e.g., reactive oxygen and nitrogen species (RONS)), physical components (e.g., electromagnetic fields and UV radiation) probably play a minor role. The effect of UV radiation most likely is negligible because UV exposure during CAP application for wound healing is far below natural UV exposure by the sun and below the general limits that have been determined for health and safety measures at work [7; 34; 35; 36]. However, a limited degree of UV exposure may have synergistic effects in combination with other components of CAP. Independent of CAP-derived electric fields, studies in bio-electrics have shown positive effects of pulsed electric fields on wound healing [37; 38]. A meta-analyses assessing the effect of electrostimulation on wound healing concluded from 15 studiesa significantly accelerated wound reduction and increased number of healed wounds compared to respective controls [39]. The application of electromagnetic fields may influence several aspects of tissue biology and hence affect tissue regeneration. It can modulate the movement of immune cells, such as macrophages and granulocytes, as well as the migration of skin cells, such as keratinocytes. Furthermore, electrostimulation is of relevance to the proliferation of fibroblasts and the stimulation of angiogenesis. Anti-bacterial effects have also been reported [40; 41; 42; 43]. Moreover, the combination of pulsed electric fields and CAP for palliative therapy in cancer patients has been discussed recently [44]. Considering this, it is conceivable that electromagnetic fields as part of CAP applications may contribute to accelerated wound healing. However, according to the current understanding, RONS are considered the most important components of CAP to mediate its biological effects. Therefore, the field of plasma medicine is also considered a field of applied redox biology [45].