# Applications of Cold Atmospheric Pressure Plasma in Density
## 3 CAPP Application in Periodontology  
Periodontal disease (PD) affects the dental support tissues and it is a major cause of tooth loss impacting on individual's function and social behaviour. Nowadays, it is well established that the presence of biofilm formation itself can lead to gingivitis but not to periodontitis. Among the bacteria involved in periodontitis development, _Porphyromonas gingivalis, Tannerella forysthia_ and _Treponema denticola_, known as red complex, are the most studied and associated to tissue destruction. In particular, _P. gingivalis_ can modulate the host response leading to bacterial unbalance into the gingival sulcus [67]. Due to the limited gain of the traditional periodontal treatment, it is necessary to find new adjuvant therapies. [PERSON] et al. [68] treated blood agar plates previously inoculated with _P. gingivalis_ (ATCC 33277) with He-CAPP jet from 5 to 11 min, and found significant difference in the diameter of inhibition zone in a time dependent manner for all periods of application when compared to the control group. Authors attributed the results to cell damage induced by RONS, though no specific analysis was performed to confirm the hypothesis. [PERSON] et al. [69] studied _P. gingivalis_ mono species biofilms using confocal microscopy and also evaluated the effect of CAPP on rabbit mucosa. Differently of [PERSON] et al. [68] that used He-CAPP, [PERSON] et al. [69] tested He/O\({}_{2}\) mixture as working gas and observed that 5 min of treatment inhibited the most bacterial cells contrary to negative control. Moreover, after one or five days of CAPP exposure for 10 min on healthy rabbit mucosa, they found no signs of irritation. [PERSON] et al. [70], in the first clinical trial using CAPP as an adjuvant therapy for non-surgical treatment in one-time application protocol, found significant gain of clinical attachment length after three months. They also observed the elimination of microorganisms in the red complex and recolonization reduction. In terms of tissue repair, [PERSON] et al. [71] evidenced that CAPP treatment for 1 and 2 min could improve cell morphology of human gingival fibroblasts and enhance the mRNA expression of TGF-\(\beta\) and VEGF. Though, when authors tested CAPP for 4 min, both morphology and growth factors expression were better in control group. Interestingly, [PERSON] et al. [72] observed that one day after a 60-s CAPP application on osteoblast-like cells, the mRNA of proinflammatory cytokines such as IL-6, IL-8 and IL-1 were upregulated as well as TNF-, COX\({}_{2}\), CCL\({}_{2}\) mRNA and COL 1, important genes for wound healing. Plus, proliferation genes such as PCNA and Ki-67 mRNA expression was significantly upregulated. More recently, most of the studies have been focused on peri-implantitis as the study of [PERSON] et al. [73]. Similar to periodontitis, peri-implantitis is an inflammatory disease dependent on biofilm that causes loss of hard and soft tissue, but it occurs around the dental implant. The authors evaluated the effects of CAPP (3 min) as an adjuvant to clinical treatment in ligature induced peri-implantitis in beagle dogs. The study compared this treatment with the traditional clinical treatment using 0.2% chlorhexidine digluconate (3 min) as decontaminant. Clinical and bone analyses (micro-CT and histology) showed better recovery in CAPP-treated group three months after treatment. Microbial recovery by PCR showed that _P. gingivalis_ and _T. forysthia_ quantity was significantly reduced when compared to control and baseline. _A. actinomycetemcomitans_ had a significant decrease in the first month that was not maintained for the next two months of follow up. [PERSON] et al. [74] showed that CAPP can reduce viability and, supposedly, quantity of _P. gingival_ biofilm in titanium discs after 1 and 3 min with no epithelial harm for gingival tissues, in vitro. The same results were obtained by [PERSON] et al. [75] using He-CAPP for 3 and 5 min.