Abstract
Hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) including continuous diffuse oxygen therapy (CDOT) are often utilized to enhance wound healing in patients with diabetic foot ulcerations. High pressure pure oxygen assists in the oxygenation of hypoxic wounds to increase perfusion. Although oxygen therapy provides wound healing benefits to some patients with diabetic foot ulcers, it is currently performed from clinical examination and imaging. Data suggest that oxygen therapy promotes wound healing via angiogenesis, the creation of new blood vessels. Molecular biomarkers relating to tissue inflammation, repair, and healing have been identified. Predictive biomarkers can be used to identify patients who will most likely benefit from this specialized treatment. In diabetic foot ulcerations, specifically, certain biomarkers have been linked to factors involving angiogenesis and inflammation, two crucial aspects of wound healing. In this review, the mechanism of how oxygen works in wound healing on a physiological basis, such as cell metabolism and growth factor signaling transduction is detailed. Additionally, observable clinical outcomes such as collagen formation, angiogenesis, respiratory burst and cell proliferation are described. The scientific evidence for the impact of oxygen on biomolecular pathways and its relationship to the outcomes in clinical research is discussed in this narrative review.
Highlights
Published: 22 June 2021Lower extremity complications in people with diabetes constitute a large worldwide burden within in already burdened population [1,2]
The role of oxygen in wound healing has long garnered interest among researchers and clinicians alike. This interest has only increased as modalities for delivery of oxygen have evolved from large hyperbaric chambers to portable, direct topical application using localized chambers and more recently to handheld, wearable systems which continuously diffuse oxygen directly into the wound bed
A separate study using direct topical oxygen on chronic diabetic foot ulcers showed significant increases in the expression of genes associated with collagen production (TGF-β, vascular endothelial growth factor (VEGF) and IL-6) during weekly follow-up visits after application of continuously diffuse oxygen (CDO) in patients with diabetic foot ulcers [50]
Summary
Lower extremity complications in people with diabetes constitute a large worldwide burden within in already burdened population [1,2]. The role of oxygen in wound healing has long garnered interest among researchers and clinicians alike This interest has only increased as modalities for delivery of oxygen have evolved from large hyperbaric chambers to portable, direct topical application using localized chambers and more recently to handheld, wearable systems which continuously diffuse oxygen directly into the wound bed. For HBOT, which relies on inspired oxygen, the availability depends on arterial pO2, vascular supply, local capillary structures and the diffusion distance for the oxygen from the capillaries to the cells Both edema and necrotic debris increase the diffusion distance. Modalities that use direct application of oxygen to the wound, such as TOT and CDOT, still require adequate vascular sufficiency, yet are significantly less dependent on local capillary structures. In the context of this review, they are relative to the levels normally found in healthy tissue surrounding a wound (40–80 mm Hg)
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