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Low-Frequency Ultrasound Reinforces Silver Nanoparticles Effect in Experimental Chronic Non-healing Purulent Wounds Treatment

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Abstract

Managing chronic non-healing wounds (CNW) is a time-consuming process accompanied by economic loss. The combination of drug-resistant microflora that is able to organize in a biofilm is the main factor of wound chronicity that requires novel treatment strategies. The current study presents the results of silver nanoparticles (AgNPs) application accompanied by low-frequency ultrasound (US) in the rat model of a purulent CNW. As a result, using AgNPs and low-frequency US demonstrated positive dynamics of wound healing and a reduction in all phases of the wound process. The combined use of AgNPs and low-frequency US made it possible to reduce the time of necrosis rejection by 6.5 days (p < 0.05), and the appearance of granulations and epithelial tissue by 3.7 and 4.7 days (p < 0.05), respectively. Simultaneous treatment by the AgNPs with low-frequency US of the purulent CNW showed accelerative tissue regeneration processes, compared to separate AgNPs or US and chlorhexidine treatment methods. A synchronous application of AgNPs with US treatment significantly improves chronic purulent wound healing and reduces the treatment period. The effectiveness of the treatment method is achieved mainly due to the bactericidal properties of AgNPs and the cleansing effect of ultrasonic cavitation.

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Data Availability

Data sets generated during the current study are available from the corresponding author Myronov PF on reasonable request.

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Acknowledgements

We highly appreciate the support given by Dr. Sukhvinder Sandhu who provided English proof-reading and corrections.

Funding

This research was supported by Horizon-Europe MSCA-SE project ARGO (№ 101086441).

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Authors and Affiliations

  1. Sumy State University, 2, Rymskogo-Korsakova st., Sumy, 40007, Ukraine

    Petro Myronov, Igor Duzhyi, Volodymyr Bugaiov, Viktoriia Holubnycha, Vladyslav Sikora, Anatoliy Opanasyuk, Anatolii Romaniuk & Maksym Pogorielov

  2. Municipal Non-Commercial Organization “Clinical Hospital № 5” of Sumy City Council, 2, Marko Vovchok st., Sumy, 40007, Ukraine

    Petro Myronov & Oleksandr Pererva

  3. Department of Clinical and Experimental Medicine, University of Foggia, Via Napoli, 20, 71122, Foggia, Italy

    Vladyslav Sikora

  4. University of Latvia, Jelgavas iela, 3, Riga, 1004, Latvia

    Maksym Pogorielov

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  1. Petro Myronov
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Contributions

P.M. proposed the idea, formulated overarching research goals and aims, and conducted an experiment on laboratory animals. I.D. developed the design and the main stages of the experiment: prepared and wrote the initial draft of the published work (including substantive translation); and reviewed and approved the final version of the manuscript. V.B. proposed an initial hypothesis for the successful combination of silver nanoparticles and low-frequency ultrasound in the treatment of chronic purulent wounds; developed and tested a model of a chronic purulent wound on laboratory animals; and wrote a draft of the literature review. V.H. prepared a mixture of microorganisms for the successful modeling of a chronic purulent wound; prepared pictures 1, 2, 3, and 8; and made a critical review, commentary, and revision of the manuscript. V.S. took histological material and conducted histological studies, calculated skin morphometric parameters, and prepared pictures 4, 5, 6, and 7. A.O. synthesized silver nanoparticles and prepared them in the required concentrations; conducted part of the experiment on laboratory animals using low-frequency ultrasound; and made suggestions on the practical application of low-frequency ultrasound in laboratory animals. A.R. conducted an analysis of histological studies; reviewed and edited the manuscript; and proposed and substantiated the repeated experiment in groups using silver nanoparticles for a more detailed histological analysis. O.P. conducted a statistical analysis of the studies using GraphPad Prism 8.0 software; and ensured the maintenance of animals in the vivarium and compliance with ethical standards during the experiment (including general anesthesia of rats). M.P. was responsible for the management and coordination of the research activity planning and execution; provided financial support for the project leading to this publication; and reviewed and approved the final version of the manuscript. All authors reviewed the manuscript.

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Correspondence to Petro Myronov.

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The authors declare that they have no conflict of interest.

Research Involving Human Participants and/or Animals

Keeping, feeding, handling of animals, and all experiments were carried out in accordance with the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines 2.0. and with Directive 2010/63/EU of the European Parliament and the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes. The Bioethics Committee of Experimental and Clinical Research of Sumy State University approved the experimental protocols (№ 4/4, 15.04.2019; № 2/9, 17.09.2021).

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The research did not involve human subjects or personal information. No informed consent is required.

Ethics Approval

All rat handling and experimental procedures fully adhere to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines 2.0. and European Directive 2010/63/EU on the Protection of Animals Used for Scientific Purposes. The Bioethics Committee of Experimental and Clinical Research of Sumy State University approved the experimental protocols (№ 4/4, 15.04.2019; № 2/9, 17.09.2021).

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Myronov, P., Duzhyi, I., Bugaiov, V. et al. Low-Frequency Ultrasound Reinforces Silver Nanoparticles Effect in Experimental Chronic Non-healing Purulent Wounds Treatment. BioNanoSci. 13, 2337–2347 (2023). https://doi.org/10.1007/s12668-023-01195-x

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