Skip to main content

Advertisement

SpringerLink
Log in

Beneficial effects of cold atmospheric plasma on inflammatory phase of diabetic foot ulcers; a randomized clinical trial

  • Research article
  • Published:
Journal of Diabetes & Metabolic Disorders Aims and scope Submit manuscript

Abstract

Purpose

The healing process is impaired in diabetic wounds like the other types of chronic wounds. Cytokines, and growth factors are valuable candidates for determination of wound vitality or duration. The aim of this study is to introduce a beneficial method to stop the inflammatory phase and infection in the wound healing process for accelerating the treatment of diabetic foot ulcers.

Methods

As a randomized controlled trial, 44 patients with diabetic foot ulcers were selected and randomized. Twenty-two patients received standard care and rest of them received SC (standard care) + CAP (cold atmospheric plasma), n = 22). Clinical examination was performed to assess the status of peripheral nerves and arteries for all patients. Cold plasma jet was used as a source of helium gas plasma generator. Plasma was irradiated on the wound 5 min, 3 times a week for 3 consecutive weeks.

Results

Applying a plasma jet was effective in wound healing. The level of inflammatory cytokines was changed. Moreover, after applying plasma the mean expression of these variables was significantly decreased (P = 0.001). Following the plasma treatment, the level of cytokines such as IL-1 (39.44 ± 7.67), IL-8 (368.30 ± 82.43), INF-γ (17.03 ± 2.62), TNFα (22.75 ± 4.02) has decreased, inflammatory factors have ameliorated over three weeks, and accelerate wound healing. After CAP exposure, the mean of the mean fraction of bacterial load counts was significantly decreased.

Conclusion

The effect of plasma irradiation on infectious diabetic foot ulcer was decreased bacterial load then accelerated wound healing by effecting on inflammatory phase in diabetic foot ulcers.

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

Access this article

Log in via an institution

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Alexiadou K, Doupis J. Management of diabetic foot ulcers. Diabetes Therapy. 2012;3(1):4.

    Article  Google Scholar 

  2. Hinchliffe R, Forsythe R, Apelqvist J, Boyko E, Fitridge R, Hong J, et al. Guidelines on diagnosis, prognosis, and management of peripheral artery disease in patients with foot ulcers and diabetes (IWGDF 2019 update). Diabetes/metabolism Research and Reviews. 2020;36:e3276-e.

  3. Hinchliffe RJ, Brownrigg J, Andros G, Apelqvist J, Boyko EJ, Fitridge R, et al. Effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral artery disease: a systematic review. Diabetes Metab Res Rev. 2016;32:136–44.

    Article  Google Scholar 

  4. Jeffcoate WJ, Harding KG. Diabetic foot ulcers. Lancet. 2003;361(9368):1545–51.

    Article  Google Scholar 

  5. Niemann C, Bondarenko AS, Constantin CG, Everson ET, Flippo KA, Gaillard SA, et al. Collisionless shocks in a large magnetized laser-plasma plume. IEEE Transactions Plasma Sci. 2011;39(11):2406–7.

    Article  CAS  Google Scholar 

  6. Bekeschus S, Schmidt A, Weltmann K-D, von Woedtke T. The plasma jet kINPen–A powerful tool for wound healing. Clin Plasma Med. 2016;4(1):19–28.

    Article  Google Scholar 

  7. Kane D. Chronic wound healing and chronic wound management. Chronic wound care: a clinical source book for healthcare professionals 4th ed Malvern, PA: HMP Communications. 2007:11–24.

  8. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008;16(5):585–601.

    Article  Google Scholar 

  9. Zubair M, Ahmad J. Role of growth factors and cytokines in diabetic foot ulcer healing: a detailed review. Rev Endocrine Metabol Disorders. 2019:1–11.

  10. Schultz GS, Wysocki A. Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen. 2009;17(2):153–62.

    Article  Google Scholar 

  11. Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219–29.

    Article  CAS  Google Scholar 

  12. Isbary G, Stolz W, Shimizu T, Monetti R, Bunk W, Schmidt H-U, et al. Cold atmospheric argon plasma treatment may accelerate wound healing in chronic wounds: results of an open retrospective randomized controlled study in vivo. Clin Plasma Med. 2013;1(2):25–30.

    Article  Google Scholar 

  13. Isbary G, Morfill G, Schmidt H, Georgi M, Ramrath K, Heinlin J, et al. A first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients. Br J Dermatol. 2010;163(1):78–82.

    Article  CAS  Google Scholar 

  14. Henry G, Garner WL. Inflammatory mediators in wound healing. Surg Clin. 2003;83(3):483–507.

    Article  Google Scholar 

  15. Ulrich C, Kluschke F, Patzelt A, Vandersee S, Czaika V, Richter H, et al. Clinical use of cold atmospheric pressure argon plasma in chronic leg ulcers: a pilot study. J Wound Care. 2015;24(5):196–203.

    Article  CAS  Google Scholar 

  16. Babaei V, Afradi H, Gohardani H, Nasseri F, Azarafza M, Teimourian S. Management of chronic diabetic foot ulcers using platelet-rich plasma. J Wound Care. 2017;26(12):784–7.

    Article  CAS  Google Scholar 

  17. Emmert S, Brehmer F, Hänßle H, Helmke A, Mertens N, Ahmed R, et al. Atmospheric pressure plasma in dermatology: Ulcus treatment and much more. Clin Plasma Med. 2013;1(1):24–9.

    Article  Google Scholar 

  18. García-Alcantara E, López-Callejas R, Morales-Ramírez PR, Peña-Eguiluz R, Fajardo-Muñoz R, Mercado-Cabrera A, et al. Accelerated mice skin acute wound healing in vivo by combined treatment of argon and helium plasma needle. Arch Med Res. 2013;44(3):169–77.

    Article  Google Scholar 

Download references

Acknowledgements

We would like to show our gratitude to all physicians and nurses in diabetes clinic affiliated to Diabetes research Center during the course of this research.

Author information

Authors and Affiliations

  1. Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Reza Amini

  2. Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Motahareh Sheikh Hosseini

  3. Department of applied physics, Amirkabir university of Technology, Tehran, Iran

    Sara Fatollah

  4. Department of applied physics, Eindhoven university of Technology, Eindhoven, The Netherlands

    Shahriar Mirpour

  5. Plasma Medicine Group, Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mahmoud Ghoranneviss

  6. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Bagher Larijani & Mohammad Reza Mohajeri-Tehrani

  7. Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Reza Khorramizadeh

Authors
  1. Mohammad Reza Amini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Motahareh Sheikh Hosseini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sara Fatollah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shahriar Mirpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mahmoud Ghoranneviss
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bagher Larijani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohammad Reza Mohajeri-Tehrani
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohammad Reza Khorramizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mohammad Reza Mohajeri-Tehrani or Mohammad Reza Khorramizadeh.

Ethics declarations

Conflict of interest disclosures

The authors have no conflict of interest to disclose.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Amini, M., Sheikh Hosseini, M., Fatollah, S. et al. Beneficial effects of cold atmospheric plasma on inflammatory phase of diabetic foot ulcers; a randomized clinical trial. J Diabetes Metab Disord 19, 895–905 (2020). https://doi.org/10.1007/s40200-020-00577-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40200-020-00577-2

Keywords

Search

Navigation