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Biocompatibility and Safety Assessment of Combined Topical Ozone and Antibiotics for Treatment of Infected Wounds
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    Biocompatibility and Safety Assessment of Combined Topical Ozone and Antibiotics for Treatment of Infected Wounds
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    • Alexander Roth
      Alexander Roth
      School of Mechanical Engineering, Purdue University, West Lafayette, Indiana 47907, United States
      Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907, United States
      Physics and Engineering Department, Taylor University, Upland, Indiana 46989, United States
    • Akshay Krishnakumar
      Akshay Krishnakumar
      Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907, United States
      School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907, United States
    • Robyn R. McCain
      Robyn R. McCain
      Center for Comparative Translational Research, Purdue University, West Lafayette, Indiana 47907, United States
    • Murali Kanaan Maruthamuthu
      Murali Kanaan Maruthamuthu
      Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
    • MacKenzie McIntosh
      MacKenzie McIntosh
      Center for Comparative Translational Research, Purdue University, West Lafayette, Indiana 47907, United States
    • Yue Xiang Chen
      Yue Xiang Chen
      Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907, United States
    • Abigail D. Cox
      Abigail D. Cox
      Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907, United States
    • Amber S. Hopf Jannasch
      Amber S. Hopf Jannasch
      Purdue Translational Pharmacology CTSI Core Facility, Purdue University, West Lafayette, Indiana 47907, United States
    • Juliane Nguyen
      Juliane Nguyen
      Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
    • Mohamed N. Seleem
      Mohamed N. Seleem
      Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, United States
    • Rahim Rahimi*
      Rahim Rahimi
      Birck Nanotechnology Center, Purdue University, West Lafayette, Indiana 47907, United States
      School of Electrical and Computer Engineering, Purdue University, West Lafayette, Indiana 47907, United States
      School of Materials Engineering, Purdue University, West Lafayette, Indiana 47907, United States
      *Email: [email protected]
      More by Rahim Rahimi
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    ACS Biomaterials Science & Engineering

    Cite this: ACS Biomater. Sci. Eng. 2023, 9, 6, 3606–3617
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    https://doi.org/10.1021/acsbiomaterials.2c01548
    Published May 26, 2023
    Copyright © 2023 American Chemical Society

    Abstract

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    Wound infections with antibiotic-resistant bacteria, particularly the Gram-negative strains, pose a substantial health risk for patients with limited treatment options. Recently topical administration of gaseous ozone and its combination with antibiotics through portable systems has been demonstrated to be a promising approach to eradicate commonly found Gram-negative strains of bacteria in wound infections. However, despite the significant impact of ozone in treating the growing number of antibiotic-resistant infections, uncontrolled and high concentrations of ozone can cause damage to the surrounding tissue. Hence, before such treatments could advance into clinical usage, it is paramount to identify appropriate levels of topical ozone that are effective in treating bacterial infections and safe for use in topical administration. To address this concern, we have conducted a series of in vivo studies to evaluate the efficacy and safety of a portable and wearable adjunct ozone and antibiotic wound therapy system. The concurrent ozone and antibiotics are applied through a wound interfaced gas permeable dressing coated with water-soluble nanofibers containing vancomycin and linezolid (traditionally used to treat Gram-positive infections) and connected to a portable ozone delivery system. The bactericidal properties of the combination therapy were evaluated on an ex vivo wound model infected with Pseudomonas aeruginosa, a common Gram-negative strain of bacteria found in many skin infections with high resistance to a wide range of currently available antibiotics. The results indicated that the optimized combination delivery of ozone (4 mg h–1) and topical antibiotic (200 μg cm–2) provided complete bacteria eradication after 6 h of treatment while having minimum cytotoxicity to human fibroblast cells. Furthermore, in vivo local and systemic toxicity studies (e.g., skin monitoring, skin histopathology, and blood analysis) on pig models showed no signs of adverse effects of ozone and antibiotic combination therapy even after 5 days of continuous administration. The confirmed efficacy and biosafety profile of the adjunct ozone and antibiotic therapy places it as a strong candidate for treating wound infection with antimicrobial-resistant bacteria and further pursuing human clinical trials.

    Copyright © 2023 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsbiomaterials.2c01548.

    • A brief description of the characterization of ozone systems used in animal studies and the description and results of the pilot biocompatibility study testing durations of ozone treatment; details of the settings used for mass spectroscopy (PDF)

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    This article is cited by 8 publications.

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    ACS Biomaterials Science & Engineering

    Cite this: ACS Biomater. Sci. Eng. 2023, 9, 6, 3606–3617
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsbiomaterials.2c01548
    Published May 26, 2023
    Copyright © 2023 American Chemical Society

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