Cold microwave plasma jets for wound healing: antimicrobial efficacy, mechanisms and changes in microbial cells

1. Boeckmann, L. et al. Cold Atmospheric Pressure Plasma in Wound Healing and Cancer Treatment. Appl. Sci. https://doi.org/10.3390/app10196898 (2020).

2. Slater, A. M., Barclay, S. J., Granfar, R. M. S. & Pratt, R. L. Fascia as a regulatory system in health and disease. Front. Neurol. https://doi.org/10.3389/fneur.2024.1458385 (2024).

3. Enoch, S. & Leaper, D. J. Basic science of wound healing. Surg. (Oxford). 26, 31–37. https://doi.org/10.1016/j.mpsur.2007.11.005 (2008).

   Google Scholar 

4. Loesche, M. et al. Temporal stability in chronic wound microbiota is associated with poor healing. J. Invest. Dermatol. 137, 237–244. https://doi.org/10.1016/j.jid.2016.08.009 (2017).

   Google Scholar 

5. Tran, K., Spry, C. Antimicrobial or Antiseptic Cleansers for Wounds. Canadian Journal of Health Technologies. 3.(6),162–169https://doi.org/10.51731/cjht.2023.671 (2023).

   Google Scholar 

6. Norman, G., Dumville, J. C., Mohapatra, D. P., Owens, G. L. & Crosbie, E. J. Antibiotics and antiseptics for surgical wounds healing by secondary intention. Cochrane Database of Systematic Reviews (2022) (2022). https://doi.org/10.1002/14651858.CD011712.pub2

7. Ngan, V., Vos, A. Antiseptics DermNet (2023). https://dermnetnz.org/topics/antiseptic#

8. Ding, X. et al. Challenges and innovations in treating chronic and acute wound infections: From basic science to clinical practice. Burns & Trauma. 10,tkac014 https://doi.org/10.1093/burnst/tkac014 (2022).

   Google Scholar 

9. Chong, L. Y. et al. Topical versus systemic antibiotics for chronic suppurative otitis media. Cochrane Database Syst. Reviews. https://doi.org/10.1002/14651858.CD013053 (2021).

10. Liu, Y. F., Ni, P. W., Huang, Y. & Xie, T. Therapeutic strategies for chronic wound infection. Chin. J. Traumatol. 25, 11–16. https://doi.org/10.1016/j.cjtee.2021.07.004 (2022).

    Google Scholar 

11. Murray, C. J. L. et al. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet 399, 629–655. https://doi.org/10.1016/S0140-6736(21)02724-0 (2022).

    Google Scholar 

12. Laroussi, M. & Akan, T. Arc-free atmospheric pressure cold plasma jets: A review. Plasma Processes Polym. 4, 777–788. https://doi.org/10.1002/ppap.200700066 (2007).

    Google Scholar 

13. Moritz, A. R. & Henriques, F. C. Studies of thermal injury: II. The relative importance of time and surface temperature in the causation of cutaneous burns. Am. J. Pathol. 23, 695–720 (1947).

    Google Scholar 

14. Fridman, A. & Friedman, G. Plasma Medicine (Wiley, 2013).

    Google Scholar 

15. Daeschlein, G. et al. Skin decontamination by low-temperature atmospheric pressure plasma jet and dielectric barrier discharge plasma. J. Hosp. Infect. 81, 177–183. https://doi.org/10.1016/j.jhin.2012.02.012 (2012).

    Google Scholar 

16. Kovalová, Z., Zahoran, M., Zahoranová, A. & Machala, Z. Streptococci biofilm decontamination on teeth by low-temperature air plasma of dc corona discharges. J. Phys. D. https://doi.org/10.1088/0022-3727/47/22/224014 (2014).

17. Maho, T. et al. Anti-Bacterial Action of Plasma Multi-Jets in the Context of Chronic Wound Healing. Appl. Sci. https://doi.org/10.3390/app11209598 (2021).

18. Mravlje, J., Regvar, M. & Vogel-Mikuš, K. Development of Cold Plasma Technologies for Surface Decontamination of Seed Fungal Pathogens: Present Status and Perspectives. J. Fungi. https://doi.org/10.3390/jof7080650 (2021).

19. Trebulová, K. et al. Antimycotic effects of the plasma gun on the yeast Candida glabrata tested on various surfaces. Plasma Processes Polym. https://doi.org/10.1002/ppap.202400057 (2024).

    Google Scholar 

20. Sutter, J. et al. Non-Thermal Plasma Reduces HSV-1 Infection of and Replication in HaCaT Keratinocytes In Vitro. Int. J. Mol. Sci. https://doi.org/10.3390/ijms25073839 (2024).

21. Lan, C. et al. Disinfection of viruses with cold atmospheric-pressure plasmas: Sources, mechanisms, and efficacy. Plasma Processes Polym. https://doi.org/10.1002/ppap.202300183 (2024).

22. Miller, V. & Bekeschus, S. Plasma-induced immunogenic cancer-cell death. Redox Biol. Plasma Med. https://doi.org/10.1201/9781003328056-12 (2024).

23. Jablonowski, L. et al. Side effects by oral application of atmospheric pressure plasma on the mucosa in mice. PLOS ONE. https://doi.org/10.1371/journal.pone.0215099 (2019).

24. Dubey, S. K. et al. Cold atmospheric plasma therapy in wound healing. Process Biochem. 112, 112–123. https://doi.org/10.1016/j.procbio.2021.11.017 (2022).

    Google Scholar 

25. Chatraie, M., Torkaman, G., Khani, M., Salehi, H. & Shokri, B. In vivo study of non-invasive effects of non-thermal plasma in pressure ulcer treatment. Sci. Rep. https://doi.org/10.1038/s41598-018-24049-z (2018).

26. Bernhardt, T. et al. Plasma medicine: Applications of cold atmospheric pressure plasma in dermatology. Oxidative Med. Cell. Longev. 2019, 1–10. https://doi.org/10.1155/2019/3873928 (2019).

    Google Scholar 

27. Weiss, M. et al. Tissue-preserving treatment with non-invasive physical plasma of cervical intraepithelial neoplasia—a prospective controlled clinical trial. Front. Med. https://doi.org/10.3389/fmed.2023.1242732 (2023).

28. Metelmann, H. R., von Woedtke, T. & Wetmann, K. D. Comprehensive Clinical Plasma Medicine (Springer, 2018).

29. Von Woedtke, T., Schmidt, A., Bekeschus, S., Wende, K., Weltmann, K. D. Plasma medicine: A field of applied redox biology. In Vivo 33, 1011–1026 (2019). https://doi.org/10.21873/invivo.11570

30. Weltmann, K. D. & von Woedtke, T. Plasma medicine—current state of research and medical application. Plasma Phys. Controlled Fusion. https://doi.org/10.1088/0741-3335/59/1/014031 (2017).

31. Kristof, J., Blajan, M. G. & Shimizu, K. A review on advancements in atmospheric plasma-based decontamination and drug delivery (invited paper). J. Electrostat. https://doi.org/10.1016/j.elstat.2025.104083 (2025).

    Google Scholar 

32. Busco, G., Robert, E., Chettouh-Hammas, N., Pouvesle, J. M. & Grillon, C. The emerging potential of cold atmospheric plasma in skin biology. Free Radic. Biol. Med. 161, 290–304. https://doi.org/10.1016/j.freeradbiomed.2020.10.004 (2020).

    Google Scholar 

33. Laroussi, M., Kong, M. G., Morfill, G. & Stolz, W. Plasma medicine – Applications of Low-Temperature Gas Plasmas in Medicine and Biology (Cambridge University Press, 2012).

    Google Scholar 

34. Winter, S., Meyer-Lindenberg, A., Wolf, G., Reese, S. & Nolff, M. C. In vitro evaluation of the decontamination effect of cold atmospheric argon plasma on selected bacteria frequently encountered in small animal bite injuries. J. Microbiol. Methods. https://doi.org/10.1016/j.mimet.2019.105728 (2020).

35. Trebulová, K., Krčma, F., Skoumalová, P., Kozáková, Z. & Machala, Z. Effects of different cold atmospheric-pressure plasma sources on the yeast Candida glabrata. Plasma Processes Polym. https://doi.org/10.1002/ppap.202300048 (2023).

36. Krčma, F. et al. Microwave micro torch generated in argon based mixtures for biomedical applications. J. Phys. D. https://doi.org/10.1088/1361-6463/aad82b (2018).

37. Misic, A. M., Gardner, S. E. & Grice, E. A. The wound microbiome: Modern approaches to examining the role of microorganisms in impaired chronic wound healing. Adv. Wound Care. 3, 502–510. https://doi.org/10.1089/wound.2012.0397 (2014).

    Google Scholar 

38. Graves, D. B. The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology. J. Phys. D. https://doi.org/10.1088/0022-3727/45/26/263001 (2012).

39. Laroussi, M. & Leipold, F. Evaluation of the roles of reactive species, heat, and UV radiation in the inactivation of bacterial cells by air plasmas at atmospheric pressure. Int. J. Mass Spectrom. 233, 81–86. https://doi.org/10.1088/1367-2630/11/11/115012 (2004).

    Google Scholar 

40. Mentheour, R. & Machala, Z. Coupled Antibacterial Effects of Plasma-Activated Water and Pulsed Electric Field. Front. Phys. https://doi.org/10.3389/fphy.2022.895813 (2022).

41. DIN. DIN SPEC 91315:2024-08. General requirements for plasma sources for the generation of cold atmospheric pressure plasma (CAP) for medical applications. Beuth Verlag. (2024).

42. Trebulová, K., Krčma, F., Kozáková, Z. & Matoušková, P. Impact of Microwave Plasma Torch on the Yeast Candida glabrata. Appl. Sci. https://doi.org/10.3390/app10165538 (2020).

43. Rouillard, A. et al. Demonstration for cold atmospheric pressure plasma jet operation and antibacterial action in microgravity. Npj Microgravity. https://doi.org/10.1038/s41526-024-00408-1 (2024).

44. KINPen^® MED product page. Neoplas med. GmbH (2021). https://neoplas-med.eu/produkt/

45. Trebulová, K. et al. Antimycotic effects of the plasma gun on the yeast Candida glabrata tested on various surfaces. Plasma Processes Polym. https://doi.org/10.1002/ppap.202400057 (2024).

    Google Scholar 

46. Uchida, G. et al. Visualization study on interaction between nonequilibrium atmospheric pressure He plasma jet and liquid solution. J. Smart Process. 8, 58–63. https://doi.org/10.7791/jspmee.8.58 (2019).

    Google Scholar 

47. Bader, H. & Hoigné, J. Determination of ozone in water by the indigo method. Water Res. 15, 449–456. https://doi.org/10.1016/0043-1354(81)90054-3 (1981).

    Google Scholar 

48. Felix, E. P. & Cardoso, A. A. Colorimetric determination of ambient ozone using indigo blue droplet. J. Braz. Chem. Soc. 17, 296–301. https://doi.org/10.1590/S0103-50532006000200012 (2006).

    Google Scholar 

49. Loupová, V. et al. Surface scan cold plasma technology for effective inhibition of Staphylococcus epidermidis and Escherichia coli. Sci. Rep. https://doi.org/10.1038/s41598-025-32902-1 (2026).

    Google Scholar 

50. Bogdanov, T. et al. Development and characterization of a novel microwave plasma source for enhanced healing in wound treatment. Processes 12, 1501. https://doi.org/10.3390/pr12071501 (2024).

    Google Scholar 

51. Bogdanov, T. et al. The effect of low-temperature microwave plasma on wound regeneration in diabetic rats. Processes 11, 3399. https://doi.org/10.3390/pr11123399 (2023).

    Google Scholar 

52. de Groot, P. W. J. et al. The cell wall of the human pathogen Candida glabrata: Differential incorporation of novel adhesin-like wall proteins. Eukaryot. Cell. 7, 1951–1964. https://doi.org/10.1128/ec.00284-08 (2008).

    Google Scholar 

53. Joshi, S. G. et al. Nonthermal dielectric-barrier discharge plasma-induced inactivation involves oxidative DNA damage and membrane lipid peroxidation in Escherichia coli. Antimicrob. Agents Chemother. 55, 1053–1062. https://doi.org/10.1128/AAC.01002-10 (2011).

    Google Scholar 

54. Dezest, M. et al. Oxidative modification and electrochemical inactivation of Escherichia coli upon cold atmospheric pressure plasma exposure. PLOS ONE. 12, e0173618. https://doi.org/10.1371/journal.pone.0173618 (2017).

    Google Scholar 

55. Barkhade, T., Nigam, K., Ravi, G., Rawat, S. & Nema, S. K. Investigating the effects of microwave plasma on bacterial cell structures, viability, and membrane integrity. Sci. Rep. https://doi.org/10.1038/s41598-025-02312-4 (2025).

56. Li, S. C. & Kane, P. M. The yeast lysosome-like vacuole: Endpoint and crossroads. Biochim. et Biophys. Acta (BBA) – Mol. Cell. Res. 1793, 650–663. https://doi.org/10.1016/j.bbamcr.2008.08.003 (2009).

    Google Scholar 

57. Shimamura, S. et al. Autophagy-inducing factor Atg1 is required for virulence in the pathogenic fungus Candida glabrata. Front. Microbiol. https://doi.org/10.3389/fmicb.2019.00027 (2019).

58. Ponpuak, M. et al. Secretory autophagy. Curr. Opin. Cell Biol. 35, 106–116. https://doi.org/10.1016/j.ceb.2015.04.016 (2015).

    Google Scholar 

59. Brown, L., Wolf, J. M., Prados-Rosales, R. & Casadevall, A. Through the wall: Extracellular vesicles in gram-positive bacteria, mycobacteria and fungi. Nat. Rev. Microbiol. 13, 620–630. https://doi.org/10.1038/nrmicro3480 (2015).

    Google Scholar 

60. Vargas, G. et al. Compositional and immunobiological analyses of extracellular vesicles released by Candida albicans: Extracellular vesicles from Candida albicans. Cell. Microbiol. 17, 389–407. https://doi.org/10.1111/cmi.12374 (2014).

    Google Scholar 

61. da Peres, R. et al. Extracellular vesicle-mediated export of fungal RNA. Sci. Rep. https://doi.org/10.1038/srep07763 (2015).

62. Ravash, N., Hesari, J., Feizollahi, E., Dhaliwal, H. K. & Roopesh, M. S. Valorization of cold plasma technologies for eliminating biological and chemical food hazards. Food Eng. Rev. 16, 22–58. https://doi.org/10.1007/s12393-023-09348-0 (2023).

    Google Scholar 

63. Zhang, H., Zhang, C. & Han, Q. Mechanisms of bacterial inhibition and tolerance around cold atmospheric plasma. Appl. Microbiol. Biotechnol. 107, 5301–5316. https://doi.org/10.1007/s00253-023-12618-w (2023).

    Google Scholar 

64. Polčic, P. & Machala, Z. Effects of non-thermal plasma on yeast Saccharomyces cerevisiae. Int. J. Mol. Sci. 22, 2247. https://doi.org/10.3390/ijms22052247 (2021).

    Google Scholar 

65. Tyczkowska-Sieroń, E., Kałużewski, T., Grabiec, M., Kałużewski, B. & Tyczkowski, J. Genotypic and phenotypic changes in Candida albicans as a result of cold plasma treatment. Int. J. Mol. Sci. https://doi.org/10.3390/ijms21218100 (2020).

66. Gupta, P., Meena, R. C. & Kumar, N. Functional characterization of Candida glabrata ORF, CAGL0M02233g for its role in stress tolerance and virulence. Microb. Pathog. https://doi.org/10.1016/j.micpath.2020.104469 (2020).

67. PlasmaDerm. PlasmaDerm plasma technology for health (2024). https://plasmaderm.de/produkte-plasmaderm/

68. PlasmActionMed Medical Plasmas https://medicalplasmas.com/en/plasmaction-med-2/

69. Hrudka, J. Automatic image analysis of the effects of non-thermal plasma on mold growth (poster at 25th International Symposium on Plasma Chemistry, Kyoto, Japan). (2023).

70. Kulich, P. et al. Subchronic Inhalation of TiO₂ nanoparticles leads to deposition in the lung and alterations in erythrocyte morphology in mice. J. Appl. Toxicol. 45, 1004–1018. https://doi.org/10.1002/jat.4759 (2025).

    Google Scholar 

Download references