# Applications of Cold Atmospheric Pressure Plasma in Density
## 2 CAPP Biological Activities  
The biological effects of CAPP enable several applications in the medical area [9]. [PERSON] [17] was the first author to report on the antibacterial effect of CAPP. After, an expressive number of manuscripts, review articles, contributions to conference and books on the antimicrobial potential of CAPP and on the physicochemical mechanisms for antimicrobial inactivation have been published. The growth control of several pathogenic microorganisms, such as Gram-positive and Gram-negative bacteria, fungal species and bacterial spores have been reported [18; 19; 20; 21; 22; 23]. Additionally, an antibofilm effect has also been observed for bacteria and fungi [24; 25; 26; 27; 28]. Interesting data point out to the anti-inflammatory and tissue repair effect induced by CAPP [29; 30]. CAPP improved wound healing in mice with induction of type I collagen and MCP-1 protein production in keratinocytes and fibroblasts [31; 32]. [PERSON] et al. [33] observed increased migration and proliferation of fibroblasts in response to the production of RONS during CAPP exposure. Similar effects were observed by [PERSON] et al. [34] and [PERSON] et al. [35]. Stimulation of keratinocytes by antioxidant pathways was also reported [30; 36]. CAPP showed positive effect in the cutaneous microcirculation, increasing  
Figure 2: Schematic representation of an APPJ. the tissue oxygen saturation and radial blood flow [37; 38] that can contribute to improved tissue repair. A remarkable feature of CAPP is its highly selective toxicity that highlights the potential for clinical treatment of infectious diseases [9; 39; 40]. This differential activity is based on differences in the cellular metabolism in presence of RONS. Eukaryotic cells exhibit protection to RONS, while prokaryotic ones do not demonstrate such protective mechanism [39; 41; 42; 43]. The disparity in the cell sizes influences response to CAPP. For instance, bacterial cells (typically between 0.2 and 10 \(\upmu\)m) have higher surface-volume ratio, which favours the plasma action, while eukaryotic cells are much bigger, from 10 to 100 \(\upmu\)m [10; 39; 42]. Moreover, the organization of eukaryotic cells into tissues additionally increases their resistance to CAPP effects. Therefore, by adjusting the treatment parameters, plasma can be used to eliminate bacteria in planktonic or biofilm forms without damage to the surrounding host tissues [9; 44; 45; 46]. In this context, treating fungal diseases has an additional challenge, as both fungal and host cells are eukaryotic. Hence, in this particular situation, the simultaneous study of fungal inhibition and toxicity to host cells is extremely important. Interestingly, there have already been some encouraging results in the literature. [PERSON] et al. [24] reported that CAPP treatment for 5 min has antibiofilm effects on _Candida albicans_ with low cytotoxicity to Vero cells [47]. In the same study, CAPP was also applied in vivo to treat oral candidiasis in mice without damaging the surrounding tissues. The ability of CAPP to induce cell death by inducing apoptosis [48] can be also very useful for therapeutic purposes, and it has been applied in the control of cancer cells. In this case, metabolic differences between healthy and malignant cells favour the selectivity of CAPP. Constant cell replications, observed in malignant cells, can expose their DNA to CAPP more frequently, favouring to the cell structural damage [39; 49; 50; 51]. RONS generated by CAPP, including hydroxyl radicals (OH\({}^{-}\)), hydrogen peroxide (H\({}_{2}\)O\({}_{2}\)), singlet oxygen (\({}^{1}\)O\({}_{2}\)), superoxide anion (O\({}^{-}\)\({}_{2}\)), atomic oxygen (O), atomic nitrogen (N), nitric oxide (NO), nitrogen trioxide (NO\({}_{3}\)), influence redox-regulated cell processes [9; 11; 18; 42; 52; 53; 54; 55; 56]. In particular, reactive oxygen species (ROS) can react with many biological macromolecules, causing oxidative structural modification and the loss of their biological function [57].