Skip to main content

Advertisement

Log in

Evaluation of efficacy of non-thermal atmospheric pressure plasma in treatment of periodontitis: a randomized controlled clinical trial

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

In this clinical study, we aim to evaluate the effectiveness of non-thermal atmospheric pressure plasma (NAPP), which is a novel procedure used in periodontal pocket decontamination adjunctive to non-surgical periodontal treatment (NSPT).

Methods

The study included 25 systemically healthy periodontitis patients. In the split-mouth design, NAPP application into the pockets, in addition to NSPT, was performed. Clinical periodontal data, gingival crevicular fluid, and subgingival plaque samples of patients were taken before and during the first and third months of treatment. Biochemical assays were conducted using enzyme-linked immunosorbent assay. Analysis of bacteria was performed with polymerase chain reaction method.

Results

There was more clinical attachment level (CAL) gain in the 3rd month in the test group (deep pockets: 3.90 mm, pockets ≥ 5 mm: 2.72 mm) compared to the control group (deep pockets: 3.40 mm, pockets ≥ 5 mm: 2.58 mm) (p < 0.05), but no significant difference between groups in CAL. Clinical periodontal parameters improved in both study groups (p < 0.05). However, the gingival index (GI) and the bleeding on probing (BOP) rate decreased more in the test group (GI: 0.55, BOP: 9.48%, and GI: 0.38, BOP: 8.46% in the 1st and 3rd months, respectively) compared to the control group (GI: 0.68, BOP: 13.43%, and GI: 0.52, BOP: 14.58%) (p < 0.05). In addition, there was no significant difference in probing depth and biochemical markers between groups (p > 0.05). It was observed that NAPP reduced the number of bacteria more than the control group in the 1st and 3rd months.

Conclusions

It was seen that the single-time NAPP application concurrent with NSPT provided additional CAL gain, elimination of putative periodontopathogens and reduced their recolonization. Longitudinal studies with larger population and longer time are required.

Clinical relevance

NSPT is an effective method for the treatment of periodontitis but bacteria recolonization that causes recurrence of the periodontal disease occurs within a short period. NAPP can reduce the recurrence of periodontal disease by providing better bacterial elimination and should, therefore, be used in maintenance of periodontitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F (2018) Periodontitis: consensus report of workgroup 2 of the 2017 world workshop on the classification of periodontal and peri-implant diseases and conditions. J Periodontol 89:S173–S182

    PubMed  Google Scholar 

  2. Mombelli A (2018) Microbial colonization of the periodontal pocket and its significance for periodontal therapy. Periodontology 2000(76):85–96. https://doi.org/10.1111/prd.12147

    Article  Google Scholar 

  3. Lang NP, Salvi GE, Sculean A (2019) Nonsurgical therapy for teeth and implants—when and why? Periodontology 79:15–21. https://doi.org/10.1111/prd.12240

    Article  Google Scholar 

  4. Giuliana G, Ammatuna P, Pizza G, Capone F, D'angelo M (1997) Occurrence of invading bacteria in radicular dentin of periodontally diseased teeth: microbiological findings. J Clin Periodontol 24:478–485

    PubMed  Google Scholar 

  5. Tribble GD, Lamont RJ (2010) Bacterial invasion of epithelial cells and spreading in periodontal tissue. Periodontol 2000(52):68–83

    Google Scholar 

  6. Jepsen K, Jepsen S (2016) Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis. Periodontology 2000(71):82–112. https://doi.org/10.1111/prd.12121

    Article  Google Scholar 

  7. Karlsson MR, Diogo Löfgren CI, Jansson HM (2008) The effect of laser therapy as an adjunct to non-surgical periodontal treatment in subjects with chronic periodontitis: a systematic review. J Periodontol 79:2021–2028

    PubMed  Google Scholar 

  8. Sgolastra F, Petrucci A, Severino M, Graziani F, Gatto R, Monaco A (2013) Adjunctive photodynamic therapy to non-surgical treatment of chronic periodontitis: a systematic review and meta-analysis. J Clin Periodontol 40:514–526

    PubMed  Google Scholar 

  9. John MT, Michalowicz BS, Kotsakis GA, Chu H (2017) Network meta-analysis of studies included in the clinical practice guideline on the nonsurgical treatment of chronic periodontitis. J Clin Periodontol

  10. Heinlin J, Morfill G, Landthaler M, Stolz W, Isbary G, Zimmermann JL, Shimizu T, Karrer S (2010) Plasma medicine: possible applications in dermatology. JDDG: Journal der Deutschen Dermatologischen Gesellschaft 8:968–976

    PubMed  Google Scholar 

  11. Fridman G, Friedman G, Gutsol A, Shekhter AB, Vasilets VN, Fridman A (2008) Applied plasma medicine. Plasma Process Polym 5:503–533

    Google Scholar 

  12. Weltmann KD, von Woedtke T (2016) Plasma medicine—current state of research and medical application. Plasma Physics and Controlled Fusion 59:014031. https://doi.org/10.1088/0741-3335/59/1/014031

    Article  Google Scholar 

  13. Yildirim ED, Ayan H, Vasilets VN, Fridman A, Guceri S, Sun W (2008) Effect of dielectric barrier discharge plasma on the attachment and proliferation of osteoblasts cultured over poly (ε-caprolactone) scaffolds. Plasma Process Polym 5:58–66

    Google Scholar 

  14. Ritts AC, Li H, Yu Q, Xu C, Yao X, Hong L, Wang Y (2010) Dentin surface treatment using a non-thermal argon plasma brush for interfacial bonding improvement in composite restoration. Eur J Oral Sci 118:510–516

    PubMed  PubMed Central  Google Scholar 

  15. Dong X, Ritts AC, Staller C, Yu Q, Chen M, Wang Y (2013) Evaluation of plasma treatment effects on improving adhesive–dentin bonding by using the same tooth controls and varying cross-sectional surface areas. Eur J Oral Sci 121:355–362

    PubMed  PubMed Central  Google Scholar 

  16. Karaman O, Kelebek S, Demirci EA, İbiş F, Ulu M, Ercan UK (2018) Synergistic effect of cold plasma treatment and RGD peptide coating on cell proliferation over titanium surfaces. Tissue Eng Regen Med 15:13–24

    PubMed  Google Scholar 

  17. Maisch T, Shimizu T, Li Y-F, Heinlin J, Karrer S, Morfill G, Zimmermann JL (2012) Decolonisation of MRSA, S. aureus and E. coli by cold-atmospheric plasma using a porcine skin model in vitro. PLoS One 7:e34610

    PubMed  PubMed Central  Google Scholar 

  18. Seo S-H, Han I, Lee HS, Choi JJ, Choi EH, Kim K-N, Park G, Kim K-M (2017) Antibacterial activity and effect on gingival cells of microwave-pulsed non-thermal atmospheric pressure plasma in artificial saliva. Sci Rep 7:8395

    PubMed  PubMed Central  Google Scholar 

  19. Ermolaeva SA, Varfolomeev AF, Chernukha MY, Yurov DS, Vasiliev MM, Kaminskaya AA, Moisenovich MM, Romanova JM, Murashev AN, Selezneva II (2011) Bactericidal effects of non-thermal argon plasma in vitro, in biofilms and in the animal model of infected wounds. J Med Microbiol 60:75–83

    PubMed  Google Scholar 

  20. Isbary G, Morfill G, Schmidt H, Georgi M, Ramrath K, Heinlin J, Karrer S, Landthaler M, Shimizu T, Steffes B (2010) A first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients. Br J Dermatol 163:78–82

    PubMed  Google Scholar 

  21. Bekeschus S, von Woedtke T, Kramer A, Weltmann K-D, Masur K (2013) Cold physical plasma treatment alters redox balance in human immune cells. Plasma Med 3

  22. Lee OJ, Ju HW, Khang G, Sun PP, Rivera J, Cho JH, Park SJ, Eden JG, Park CH (2016) An experimental burn wound-healing study of non-thermal atmospheric pressure microplasma jet arrays. J Tissue Eng Regen Med 10:348–357

    PubMed  Google Scholar 

  23. Kwon J-S, Kim YH, Choi EH, Kim C-K, Kim K-N, Kim K-M (2016) Non-thermal atmospheric pressure plasma increased mRNA expression of growth factors in human gingival fibroblasts. Clin Oral Investig 20:1801–1808

    PubMed  Google Scholar 

  24. Kalghatgi S, Friedman G, Fridman A, Clyne AM (2010) Endothelial cell proliferation is enhanced by low dose non-thermal plasma through fibroblast growth factor-2 release. Ann Biomed Eng 38:748–757

    PubMed  Google Scholar 

  25. Arndt S, Landthaler M, Zimmermann JL, Unger P, Wacker E, Shimizu T, Li Y-F, Morfill GE, Bosserhoff A-K, Karrer S (2015) Effects of cold atmospheric plasma (CAP) on ß-defensins, inflammatory cytokines, and apoptosis-related molecules in keratinocytes in vitro and in vivo. PLoS One 10:e0120041

    PubMed  PubMed Central  Google Scholar 

  26. Nakajima Y, Mukai K, Rahayu HSE, Nur M, Ishijima T, Enomoto H, Uesugi Y, Sugama J, Nakatani T (2014) Cold plasma on full-thickness cutaneous wound accelerates healing through promoting inflammation, re-epithelialization and wound contraction. Clin Plasma Med 2:28–35

    Google Scholar 

  27. Haertel B, von Woedtke T, Weltmann K-D, Lindequist U (2014) Non-thermal atmospheric-pressure plasma possible application in wound healing. Biomol Ther (Seoul) 22:477

    Google Scholar 

  28. Heinlin J, Zimmermann JL, Zeman F, Bunk W, Isbary G, Landthaler M, Maisch T, Monetti R, Morfill G, Shimizu T (2013) Randomized placebo-controlled human pilot study of cold atmospheric argon plasma on skin graft donor sites. Wound Repair Regen 21:800–807

    PubMed  Google Scholar 

  29. Brehmer F, Haenssle H, Daeschlein G, Ahmed R, Pfeiffer S, Görlitz A, Simon D, Schön M, Wandke D, Emmert S (2015) Alleviation of chronic venous leg ulcers with a hand-held dielectric barrier discharge plasma generator (PlasmaDerm® VU-2010): results of a monocentric, two-armed, open, prospective, randomized and controlled trial (NCT01415622). J Eur Acad Dermatol Venereol 29:148–155

    PubMed  Google Scholar 

  30. Tomasi C, Schander K, Dahlen G, Wennstrom JL (2006) Short-term clinical and microbiologic effects of pocket debridement with an Er:YAG laser during periodontal maintenance. J Periodontol 77:111–118. https://doi.org/10.1902/jop.2006.77.1.111

    Article  PubMed  Google Scholar 

  31. Sanz-Sanchez I, Ortiz-Vigon A, Herrera D, Sanz M (2016) Microbiological effects and recolonization patterns after adjunctive subgingival debridement with Er:YAG laser. Clin Oral Investig 20:1253–1261. https://doi.org/10.1007/s00784-015-1617-y

    Article  PubMed  Google Scholar 

  32. Silness J, Löe H (1964) Periodontal disease in pregnancy II. Correlation between oral hygiene and periodontal condition. Acta Odontol Scand 22:121–135

    PubMed  Google Scholar 

  33. Löe H, Silness J (1963) Periodontal disease in pregnancy I. Prevalence and severity. Acta Odontol Scand 21:533–551

    PubMed  Google Scholar 

  34. Ainamo J, Bay I (1975) Problems and proposals for recording gingivitis and plaque. Int Dent J 25:229–235

    PubMed  Google Scholar 

  35. Karaman O, Kumar A, Moeinzadeh S, He X, Cui T, Jabbari E (2016) Effect of surface modification of nanofibres with glutamic acid peptide on calcium phosphate nucleation and osteogenic differentiation of marrow stromal cells. J Tissue Eng Regen Med 10

  36. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45

    PubMed  PubMed Central  Google Scholar 

  37. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods 25:402–408

    PubMed  Google Scholar 

  38. Shi Q, Song K, Zhou X, Xiong Z, Du T, Lu X, Cao Y (2015) Effects of non-equilibrium plasma in the treatment of ligature-induced peri-implantitis. J Clin Periodontol 42:478–487

    PubMed  Google Scholar 

  39. Pérez-Chaparro PJ, Duarte PM, Shibli JA, Montenegro S, Lacerda Heluy S, Figueiredo LC, Faveri M, Feres M (2016) The current weight of evidence of the microbiologic profile associated with peri-implantitis: a systematic review. J Periodontol 87:1295–1304

    PubMed  Google Scholar 

  40. Holt SC, Ebersole JL (2005) Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the ‘red complex’, a prototype polybacterial pathogenic consortium in periodontitis. Periodontol 2000(38):72–122

    Google Scholar 

  41. Umeda M, Takeuchi Y, Noguchi K, Huang Y, Koshy G and Ishikawa I (2004) Effects of nonsurgical periodontal therapy on the microbiota. Periodontol 2000 36:98–120

  42. Cobb CM (1996) Non-surgical pocket therapy: mechanical. Ann Periodontol 1:443–490

    PubMed  Google Scholar 

  43. Sbordone L, Ramaglia L, Gulletta E, Iacono V (1990) Recolonization of the subgingival microflora after scaling and root planing in human periodontitis. J Periodontol 61:579–584

    PubMed  Google Scholar 

  44. Soeroso Y, Akase T, Sunarto H, Kemal Y, Salim R, Octavia M, Viandita A, Setiawan J, Bachtiar B (2017) The risk reduction of recurrent periodontal pathogens of local application minocycline hCl 2% gel, used as an adjunct to scaling and root planing for chronic periodontitis treatment. Ther Clin Risk Manag 13:307

    PubMed  PubMed Central  Google Scholar 

  45. Kovalova Z, Zahoran M, Zahoranová A, Machala Z (2014) Streptococci biofilm decontamination on teeth by low-temperature air plasma of dc corona discharges. J Phys D Appl Phys 47:224014

    Google Scholar 

  46. Shekhter AB, Serezhenkov VA, Rudenko TG, Pekshev AV, Vanin AF (2005) Beneficial effect of gaseous nitric oxide on the healing of skin wounds. Nitric Oxide 12:210–219

    PubMed  Google Scholar 

  47. Zoellner H, Chapple CC, Hunter N (2002) Microvasculature in gingivitis and chronic periodontitis: disruption of vascular networks with protracted inflammation. Microsc Res Tech 56:15–31

    PubMed  Google Scholar 

  48. Hou LT, Liu CM, Rossomando EF (1995) Crevicular interleukin-1β in moderate and severe periodontitis patients and the effect of phase I periodontal treatment. J Clin Periodontol 22:162–167

    PubMed  Google Scholar 

  49. Prapulla DV, Sujatha PB, Pradeep A (2007) Gingival crevicular fluid VEGF levels in periodontal health and disease. J Periodontol 78:1783–1787

    PubMed  Google Scholar 

  50. Gamonal J, Acevedo A, Bascones A, Jorge O, Silva A (2000) Levels of interleukin-1β,-8, and-10 and RANTES in gingival crevicular fluid and cell populations in adult periodontitis patients and the effect of periodontal treatment. J Periodontol 71:1535–1545

    PubMed  Google Scholar 

  51. Choi J-H, Lee H-J, Hong J-W, Kim G-C (2015) The treatment with non-thermal plasma on human keratinocyte can block TNF-α and IFN-γ mediated pro-inflammatory gene expressions. Book title, IEEE

    Google Scholar 

  52. Smail-Faugeron V, Fron-Chabouis H, Courson F, Durieux P (2014) Comparison of intervention effects in split-mouth and parallel-arm randomized controlled trials: a meta-epidemiological study. BMC Med Res Methodol 14:64. https://doi.org/10.1186/1471-2288-14-64

    Article  PubMed  PubMed Central  Google Scholar 

  53. Husejnagic S, Lettner S, Laky M, Georgopoulos A, Moritz A, Rausch-Fan X (2019) Photoactivated disinfection in periodontal treatment: a randomized controlled clinical split-mouth trial. J Periodontol

  54. Berakdar M, Callaway A, Eddin MF, Roß A, Willershausen B (2012) Comparison between scaling-root-planing (SRP) and SRP/photodynamic therapy: six-month study. Head Face Med 8:12

    PubMed  PubMed Central  Google Scholar 

  55. Smiley CJ, Tracy SL, Abt E, Michalowicz BS, John MT, Gunsolley J, Cobb CM, Rossmann J, Harrel SK, Forrest JL (2015) Systematic review and meta-analysis on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts. J Am Dent Assoc 146:508–524.e5

    PubMed  Google Scholar 

  56. Megally A, Zekeridou A, Cancela J, Giannopoulou C, Mombelli A (2019) Short ultrasonic debridement with adjunctive low-concentrated hypochlorite/amino acid gel during periodontal maintenance: randomized clinical trial of 12 months. Clin Oral Investig:1–9

Download references

Funding

This study was funded by The Scientific and Technological Research Council of Turkey (TÜBİTAK) with the project number 315S274.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Serhat Köseoğlu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This prospective, split-mouth, double-masked, placebo controlled randomized clinical trial (RCT) was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2008, and the study protocol was approved by the Research Ethics Committee of İzmir Katip Çelebi University of Medical Sciences (Date:16.09.2015, version number:1). This study was registered at Turkish Medicines And Medical Devices Agency (number: 71146310 [2015-AC-CE-00129]).

Informed consent

Informed consent was obtained from all patients in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Küçük, D., Savran, L., Ercan, U.K. et al. Evaluation of efficacy of non-thermal atmospheric pressure plasma in treatment of periodontitis: a randomized controlled clinical trial. Clin Oral Invest 24, 3133–3145 (2020). https://doi.org/10.1007/s00784-019-03187-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-019-03187-2

Keywords

Navigation