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Mechanistic insights and international use cases of continuous topical oxygen therapy in wound management

Windy Cole, Harikrishna KR Nair, Sagar U Nigwekar, Viviana Gonçalves, Liezl Naude, Wolmark Xiques Molina, Noel B Natoli, Andrew Camilleri
22 December 2025
Introduction: Chronic wounds are a growing global health concern, often complicated by tissue hypoxia and impaired healing. Continuous topical oxygen therapy (cTOT) has emerged as a promising adjunctive treatment that delivers sustained oxygen directly to the wound bed, supporting cellular metabolism, immune modulation, angiogenesis and tissue regeneration. Methods: This article reviews the mechanistic basis of cTOT, including its effects on hypoxia-inducible factors, mitochondrial ATP production, immune cell function and extracellular matrix remodelling. Eight international case studies were collected from six countries, each documenting the use of cTOT in managing complex, non-healing wounds. Cases included diabetic foot ulcers, vasculitis, burns, surgical dehiscence, calciphylaxis and osteoradionecrosis. Results: All cases demonstrated significant clinical improvement following cTOT, with complete wound closure achieved in each instance. Healing timelines ranged from 4 to 29 weeks, depending on wound type and severity. The therapy was well-tolerated, easily integrated into standard care protocols, and effective across diverse healthcare settings and patient populations. Conclusions: cTOT is a mechanistically sound, globally adaptable adjunct for managing hard-to-heal wounds. Its demonstrated efficacy across a range of wound types supports its broader integration into comprehensive wound care strategies. Further research is warranted to optimise treatment protocols and expand clinical indications.
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