Document Type : Original Article(s)

Authors

1 Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Plasma Physics and Nuclear Fusion Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran

3 Department of Pathology, , Shahid Beheshti University of Medical Sciences, Tehran, Iran

4 Iran Helal Institute of Applied-Science and Technology, Red Crescent Society of Iran, Tehran, Iran

10.30476/mejc.2024.102257.2079

Abstract

Background: Cold atmospheric plasma (CAP) may reduce bacteria and aid wound healing through reactive oxygen species. Recent trials support CAP for chronic wounds, but its effectiveness is not well-proven. This studyevaluates the efficacy of CAP on wound healing rate.
Method: This cross-sectional study was conducted sequentialy to investigate the impact of CAP intervention on wound healing in rats over a period from 2022 to 2023. The study was carried out at the Atomic Energy Organization of Iran.A total number of 16 ratswere divided into three groups based on the duration of CAP exposure: Group 1 (0 minutes), Group 2 (3 minutes), and Group 3 (5 minutes). Continuous variables were reported as mean ± SD. Group differences were analyzed using ANOVA or Kruskal-Wallis. A P-value <0.05 was considered statistically significant.
Results: Day zero analysis revealed an absence of acute inflammatory response, with neutrophils consistently absent across all groups. Lymphocytes were predominantly absent, with a mild presence observed in most cases. Granulation tissue was mainly absent, and when present, it exhibited minimal extent. Blood vessel count was mostly below 20 per 10 high-power fields, with a slightly higher count in the 5 minute CAP intervention group. Fibroblasts were mostly absent, and when present, they were found in minimal extent. Ulcers, keloids, and hypertrophic scars were largely absent in all cases. Day seven and fourteen analyses revealed no significant differences between the left and right sides of the wounds for most variables.
Conclusion: CAP therapy showed promise for acute wound healing in rats, with minimal inflammation and scar formation. Further research is needed to optimize its use.

Highlights

Atieh Akbari (Google Scholar)

Mohammad Esmaeil Akbari (Google Scholar)

Keywords

Main Subjects

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.30476/mejc.2024.102257.2079

  1. Boeckmann L, Schäfer M, Bernhardt T, Semmler ML, Jung O, Ojak G, et al. Cold atmospheric pressure plasma in wound healing and cancer treatment. Appl Sci. 2020;10(19):6898. doi: 10.3390/app10196898.
  2. Garner AL, Mehlhorn TA. A review of cold atmospheric pressure plasmas for trauma and acute care. Front Phys. 2021;9:774. doi: 10.3389/fphy.2021.786381.
  3. Bender C, Partecke LI, Kindel E, Döring F, Lademann J, Heidecke CD, et al. The modified HET-CAM as a model for the assessment of the inflammatory response to tissue tolerable plasma. Toxicol In Vitro. 2011;25(2):530-7. doi: 10.1016/j.tiv.2010.11.012.
  4. Klämpfl TG, Isbary G, Shimizu T, Li YF, Zimmermann JL, Stolz W, et al. Cold atmospheric air plasma sterilization against spores and other microorganisms of clinical interest. Appl Environ Microbiol. 2012;78(15):5077-82. doi: 10.1128/AEM.00583-12.
  5. Lademann O, Kramer A, Richter H, Patzelt A, Meinke MC, Roewert-Huber J, et al. Antisepsis of the follicular reservoir by treatment with tissue-tolerable plasma (TTP). Laser Phys Lett. 2011;8(4):313. doi: 10.1002/lapl.201010123.
  6. Lademann O, Richter H, Meinke MC, Patzelt A, Kramer A, Hinz P, et al. Drug delivery through the skin barrier enhanced by treatment with tissue-tolerable plasma. Exp Dermatol. 2011;20(6):488-90. doi: 10.1111/j.1600-0625.2010.01245.x.
  7. Shimizu T, Zimmermann J, Morfill G. The bactericidal effect of surface micro-discharge plasma under different ambient conditions. New J Phys. 2011;13(2):023026. doi: 10.1088/1367-2630/13/2/023026.
  8. Kalghatgi S, Friedman G, Fridman A, Clyne AM. Endothelial cell proliferation is enhanced by low dose non-thermal plasma through fibroblast growth factor-2 release. Ann Biomed Eng. 2010;38(3):748-57. doi: 10.1007/s10439-009-9868-x.
  9. Nosenko T, Shimizu T, Morfill G. Designing plasmas for chronic wound disinfection. New J Phys. 2009;11(11):115013. doi:10.1088/1367-2630/11/11/115013.
  10. Pompl R, Jamitzky F, Shimizu T, Steffes B, Bunk W, Schmidt HU, et al. The effect of low-temperature plasma on bacteria as observed by repeated AFM imaging. New J Phys. 2009;11(11):115023. doi:10.1088/1367-2630/11/11/115023.
  11. Tipa RS, Kroesen GM. Plasma-stimulated wound healing. IEEE Trans Plasma Sci. 2011;39(11):2978-9. doi:10.1109/TPS.2011.2159868.
  12. Braný D, Dvorská D, Halašová E, Škovierová H. Cold Atmospheric plasma: A powerful tool for modern medicine. Int J Mol Sci. 2020;21(8):2932. doi: 10.3390/ijms21082932. PMID: 32331263; PMCID: PMC7215620.
  13. Boekema B, Stoop M, Vlig M, van Liempt J, Sobota A, Ulrich M, et al. Antibacterial and safety tests of a flexible cold atmospheric plasma device for the stimulation of wound healing. Appl Microbiol Biotechnol. 2021;105(5):2057-70. doi: 10.1007/s00253-021-11166-5. PMID: 33587156; PMCID: PMC7906937.
  14. Assadian O, Ousey KJ, Daeschlein G, Kramer A, Parker C, Tanner J, et al. Effects and safety of atmospheric low-temperature plasma on bacterial reduction in chronic wounds and wound size reduction: A systematic review and meta-analysis. Int Wound J. 2019;16(1):103-11. doi: 10.1111/iwj.12999. PMID: 30311743; PMCID: PMC7379569.
  15. Ma Y, Sun T, Ren K, Min T, Xie X, Wang H, et al. Applications of cold atmospheric plasma in immune-mediated inflammatory diseases via redox homeostasis: evidence and prospects. Heliyon. 2023;9(12):e22568. doi: 10.1016/j.heliyon.2023.e22568. PMID: 38107323; PMCID: PMC10724573.
  16. Dang CP, Weawseetong S, Charoensappakit A, Sae-Khow K, Thong-Aram D, Leelahavanichkul A. Non-thermal atmospheric pressure argon-sourced plasma flux promotes wound healing of burn wounds and burn wounds with infection in mice through the anti-inflammatory macrophages. Appl Sci. 2021;11:5343. doi:10.3390/app11125343.
  17. Hiller J, Stratmann B, Timm J, Costea TC, Tschoepe D. Enhanced growth factor expression in chronic diabetic wounds treated by cold atmospheric plasma. Diabet Med. 2022;39(6):e14787. doi: 10.1111/dme.14787. PMID: 35007358.
  18. Tehranian A, Esfehani-Mehr B, Pirjani R, Rezaei N, Sadat Heidary S, Sepidarkish M. Application of Autologous Platelet-Rich Plasma (PRP) on wound healing after caesarean section in high-risk patients. Iran Red Crescent Med J. 2016;18(7):e34449. doi: 10.5812/ircmj.34449. PMID: 27660723; PMCID: PMC5027131.
  19. Barjasteh A, Kaushik N, Choi EH, Kaushik NK. Cold atmospheric pressure plasma: A growing paradigm in diabetic wound healing-mechanism and clinical significance. Int J Mol Sci. 2023;24(23):16657. doi: 10.3390/ijms242316657. PMID: 38068979; PMCID: PMC10706109.