{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T11:44:55Z","timestamp":1764071095945,"version":"3.45.0"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nursing Reports"],"abstract":"<jats:p>Background\/Objectives: Wound management remains a clinical challenge, particularly in chronic and refractory conditions. Ozone, due to its antimicrobial, anti-inflammatory, and tissue-regenerative properties, has emerged as promising adjuvant therapy. This integrative re-view aimed to critically analyze the therapeutic effects, routes of administration, benefits, and limitations of ozone in wound treatment. Methods: The review followed the Joanna Briggs In-stitute methodology and the PRISMA 2020 guidelines. Studies were identified through compre-hensive search in the SCOPUS, CINAHL Ultimate, MEDLINE Ultimate, and MedicLatina data-bases, with no time restrictions. Inclusion criteria encompassed primary studies involving adults (\u226518 years) with wounds treated with ozone. The methodological quality of the selected studies was assessed using the tools recommended by JBI. Results: Nine reports published between 2019 and 2025 met the inclusion criteria. The findings consistently demonstrated clinical benefits of ozone therapy, including accelerated wound healing, pain reduction, and infection control. The forms of application included ozonated water, ozonated olive oil, and gaseous ozone. However, heterogeneity was observed in ozone concentration, frequency, and treatment duration. The methodological quality of the included studies ranged from moderate to high. Conclusions: The available evidence indicates that ozone may represent promising adjuvant treatment for certain types of wounds; however, the quality and independence of the existing studies are limited, and the lack of standardized protocols as well as methodological variability restrict the generalizability of the findings. Therefore, more robust clinical trials are needed to strengthen the evidence base and support its clinical implementation.<\/jats:p>","DOI":"10.3390\/nursrep15120414","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T10:46:18Z","timestamp":1764067578000},"page":"414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Topical Ozone as an Adjuvant Therapy in Wound Management: An Integrative Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6077-4150","authenticated-orcid":false,"given":"Cristina Barroso","family":"Pinto","sequence":"first","affiliation":[{"name":"RISE-Health, Nursing School of Porto, University of Porto, 4200-072 Porto, Portugal"}]},{"given":"Adelino","family":"Pinto","sequence":"additional","affiliation":[{"name":"Gaia\/Espinho Local Health Unit, 4434-502 Vila Nova de Gaia, Portugal"}]},{"given":"Manuela","family":"Barroso","sequence":"additional","affiliation":[{"name":"Gaia\/Espinho Local Health Unit, 4434-502 Vila Nova de Gaia, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8917-6741","authenticated-orcid":false,"given":"Telma","family":"Coelho","sequence":"additional","affiliation":[{"name":"T\u00e3mega e Sousa Local Health Unit, 4564-007 Guilhufe, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2422-3626","authenticated-orcid":false,"given":"Sandra","family":"Costa","sequence":"additional","affiliation":[{"name":"RISE-Health, School of Health, Santar\u00e9m Plytechnic University, 2001-904 Santar\u00e9m, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1089\/wound.2019.1021","article-title":"Skin Structure-Function Relationships and the Wound Healing Response to Intrinsic Aging","volume":"9","author":"Blair","year":"2020","journal-title":"Adv. Wound Care"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tottoli, E., Dorati, R., Genta, I., Chiesa, E., Pisani, S., and Conti, B. (2020). Skin Wound Healing Process and New Emerging Technologies for Skin Wound Care and Regeneration. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12080735"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mamun, A., Shao, C., Geng, P., Wang, S., and Xiao, J. (2024). Recent advances in molecular mechanisms of skin wound healing and its treatments. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1395479"},{"key":"ref_4","first-page":"e2018","article-title":"Elaboration of an algorithm for wound evaluation and treatment","volume":"16","author":"Cunha","year":"2018","journal-title":"Estima\u2014Braz. J. Enterostomal. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/s41580-024-00715-1","article-title":"Cellular and molecular mechanisms of skin wound healing","volume":"25","author":"Martin","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1089\/wound.2019.1095","article-title":"The Potential Impact of Social Genomics on Wound Healing","volume":"9","author":"Fayne","year":"2020","journal-title":"Adv. Wound Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/wrr.12683","article-title":"The humanistic and economic burden of chronic wounds: A systematic review","volume":"27","author":"Olsson","year":"2018","journal-title":"Wound Repair Regen."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1089\/wound.2023.0150","article-title":"Human Wounds and its Burden: Updated 2022 Compendium of Estimates","volume":"12","author":"Sen","year":"2023","journal-title":"Adv. Wound Care"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hashim, N., Babiker, R., Dasnadi, S., Islam, M., Chaitanya, N., Mohammed, R., Farghal, N.S., Gobara, B., and Rahman, M.M. (2025). The impact of ozone on periodontal cell line viability and function. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47020072"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Viebahn-Haensler, R., and Fern\u00e1ndez, O. (2021). Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157890"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.addr.2018.02.001","article-title":"Nanomedicines and gene therapy for the delivery of growth factors to improve perfusion and oxygenation in wound healing","volume":"129","author":"Desmet","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"54","DOI":"10.4103\/2045-9912.279985","article-title":"Ozonated oil in wound healing: What has already been proven?","volume":"10","author":"Anzolin","year":"2020","journal-title":"Med. Gas. Res."},{"key":"ref_13","first-page":"133","article-title":"The Effectivity of Ozonated VCO on Healing Full Grafted Skin graft Study on Progenitor Cell Endothelial Proliferation and Angiogenesis in Sprague Dawley Mice","volume":"8","author":"Sidauruk","year":"2021","journal-title":"Med. Hosp. J. Clin. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.actbio.2022.09.077","article-title":"Oxygen-releasing hydrogels promote burn healing under hypoxic conditions","volume":"154","author":"Bai","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.ASW.0000874176.25479.2c","article-title":"Ozone Therapy in the Comprehensive Treatment of Leg Ulcers: Case Report","volume":"35","author":"Pasek","year":"2022","journal-title":"Adv. Skin. Wound Care"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pasek, J., Kowalska, A., and Nowak, M. (2023). Topical hyperbaric oxygen therapy versus local ozone therapy in healing of venous leg ulcers. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20031967"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.3390\/clinpract14050169","article-title":"Effect of Treatment of Neuropathic and Ischemic Diabetic Foot Ulcers with the Use of Local Ozone Therapy Procedures\u2014An Observational Single Center Study","volume":"14","author":"Pasek","year":"2024","journal-title":"Clin. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.36489\/feridas.2021v9i49p1773-1778","article-title":"Uso do oz\u00f4nio no tratamento de feridas: Revis\u00e3o de escopo","volume":"9","author":"Nobre","year":"2021","journal-title":"Rev. Feridas"},{"key":"ref_19","first-page":"13","article-title":"A aplicabilidade e os benef\u00edcios da ozonioterapia no tratamento de feridas: Uma revis\u00e3o integrativa. In: Ci\u00eancias Biol\u00f3gicas e da Sa\u00fade: Integrando Saberes em Diferentes Contextos","volume":"1","author":"Targino","year":"2022","journal-title":"Ed. Cient."},{"key":"ref_20","unstructured":"Joanna Briggs Institute (2020). Checklist for Systematic Reviews and Research Syntheses, The Joanna Briggs Institute. Available online: https:\/\/jbi.global\/."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Li, L., Feng, A., Lu, J., Liu, H., Xue, W., and Cui, H. (2025). Evaluating the Therapeutic Efficacy of Ozone Liquid Dressing in Healing Wounds Associated with Bullous Pemphigoid. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-90563-6"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"626","DOI":"10.5114\/ada.2024.145477","article-title":"Impact of Ozone Concentration on the Treatment Effectiveness of Diabetic Foot Syndrome: A Pilot Single-Centre Study","volume":"41","author":"Pasek","year":"2024","journal-title":"Postepy Dermatol. Alergol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sun, H., Heng, H., Liu, X., Geng, H., and Liang, J. (2024). Evaluation of the healing potential of short-term ozone therapy for the treatment of diabetic foot ulcers. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1304034"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5491","DOI":"10.15419\/bmrat.v10i1.787","article-title":"Effectiveness of Combined Application of Cryosurgical Method and Local Ozone Therapy in Patients with Oral Leukoplakia","volume":"10","author":"Darenskaya","year":"2023","journal-title":"Biomed. Res. Ther."},{"key":"ref_26","first-page":"108","article-title":"Ruptured Ulcerated and Inflamed Gout Tophi with Deep Soft Tissue Infection of Left Foot\u2014When Rheumatology Meets Surgery: A Case Report Treated with Local Ozone Therapy","volume":"31","author":"Marinova","year":"2023","journal-title":"Rheumatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"371","DOI":"10.14444\/6050","article-title":"Severe Spinal Surgery Infection and Local Ozone Therapy as Complementary Treatment: A Case Report","volume":"13","author":"Buric","year":"2019","journal-title":"Int. J. Spine Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1365-2648.2005.03621.x","article-title":"The integrative review: Updated methodology","volume":"52","author":"Whittemore","year":"2005","journal-title":"J. Adv. Nurs."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1590\/S0104-07072008000400018","article-title":"Integrative review: Research method for the incorporation of evidence in health and nursing","volume":"17","author":"Mendes","year":"2008","journal-title":"Texto Contexto Enferm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1590\/s1679-45082010rw1134","article-title":"Integrative review: What is it? How to do it?","volume":"8","author":"Souza","year":"2010","journal-title":"Einstein"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1177\/1534484316671606","article-title":"Writing integrative literature reviews: Using the past and present to explore the future","volume":"15","author":"Torraco","year":"2016","journal-title":"Hum. Resour. Dev. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Roth, A., Elkashif, A., Selvamani, V., Stucky, R., Seleem, M., Ziaie, B., and Rahimi, R. (2020). Wearable and flexible ozone generating system for treatment of infected dermal wounds. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00458"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1007\/s00784-024-05961-3","article-title":"Systemic ozone therapy as an adjunctive treatment in guided bone regeneration: A histomorphometrical and immunohistochemical study in rats","volume":"28","author":"Baggio","year":"2024","journal-title":"Clin. Oral. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e20210046","DOI":"10.1590\/1807-2577.04621","article-title":"Effect of systemic ozone therapy as a biomodulator of tissue regeneration and inflammatory response in rats","volume":"50","author":"Pires","year":"2021","journal-title":"Rev. Odontol. UNESP"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e076739","DOI":"10.1136\/bmjopen-2023-076739","article-title":"Use of oxygen-ozone therapy to improve the effectiveness of antibiotic treatment on infected arthroplasty: Protocol for a superiority, open-label, multicentre, randomised, parallel trial","volume":"14","author":"Cascini","year":"2024","journal-title":"BMJ Open"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1021\/acsbiomaterials.2c01548","article-title":"Biocompatibility and safety assessment of combined topical ozone and antibiotics for treatment of infected wounds","volume":"9","author":"Roth","year":"2023","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1080\/01919512.2012.717847","article-title":"Concept\u2014Guidelines and Treatment Strategies","volume":"34","author":"Fahmy","year":"2012","journal-title":"Ozone Sci. Eng."}],"container-title":["Nursing Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4403\/15\/12\/414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T11:42:14Z","timestamp":1764070934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4403\/15\/12\/414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["nursrep15120414"],"URL":"https:\/\/doi.org\/10.3390\/nursrep15120414","relation":{},"ISSN":["2039-4403"],"issn-type":[{"value":"2039-4403","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,25]]}}}