Adequate tissue oxygenation is a cornerstone of effective skin wound healing; insufficient oxygen contributes to impaired repair and the development of chronic wounds. Obstructive sleep apnea (OSA) causes repetitive cycles of desaturation and reoxygenation during sleep, referred to as intermittent hypoxia (IH). The authors propose that OSA may impair wound healing both indirectly—by increasing the prevalence of comorbidities such as diabetes, hypertension, and obesity—and directly through the cellular and tissue effects of IH.
The authors searched PubMed/MEDLINE, Scopus, and Web of Science through August 2026 to identify preclinical and clinical studies addressing OSA, IH, and wound healing. This narrative review integrates cellular mechanisms, available preclinical evidence (largely from in vitro work), and heterogeneous clinical data. The review is presented as the first synthesis to combine these levels of evidence on this specific topic.
Normal wound repair depends on timely oxygen delivery to support cellular metabolism, angiogenesis, and immune function. Hypoxia is known to impair several phases of healing and contribute to chronicity. The review highlights the distinction between different hypoxic states: acute hypoxia, chronic sustained hypoxia, and the repetitive intermittent hypoxia characteristic of OSA; each elicits distinct molecular responses that may differentially influence repair processes.
Intermittent hypoxia associated with OSA activates molecular pathways that differ from those triggered by sustained hypoxia. The cyclic pattern of desaturation and reoxygenation can promote oxidative stress and unique signaling cascades. Given the high global prevalence of OSA—reported as nearly one billion adults—and the large proportion of undiagnosed cases (up to 80%), IH represents a widespread, potentially underrecognized exposure relevant to tissue repair.
The review describes several IH-driven mechanisms that could impede wound healing:
Reduced antioxidant capacity, increasing susceptibility to oxidative damage during reoxygenation phases.
Sustained inflammation, with shifts in immune cell phenotypes that may prolong the inflammatory phase and delay progression to proliferative and remodeling phases.
Sympathetic activation, which can alter perfusion and tissue responses.
Endothelial dysfunction, impairing angiogenesis and microvascular responses necessary for oxygen delivery and nutrient exchange.
These mechanisms provide biological plausibility for a direct effect of OSA/IH on impaired tissue repair.
Preclinical data are limited and primarily derive from in vitro scratch assays. Key findings reported in these models include:
IH exposure delays wound closure in cell-based assays.
Downregulation of transcriptional regulators and angiogenic factors, specifically HIF-2α and VEGF, under IH conditions.
Polarization of macrophages toward a pro-inflammatory phenotype, which could extend the inflammatory phase and inhibit repair.
The authors note the relative scarcity of in vivo animal studies and emphasize that most experimental work to date is confined to simplified in vitro systems, limiting direct translation to clinical wound healing contexts.
Clinical data linking OSA to impaired wound healing are described as limited and heterogeneous. Relevant clinical observations summarized in the review include:
In studies of diabetic foot ulcers, a high risk of OSA was associated with a doubled risk of poor healing.
Reports of improved ulcer healing after continuous positive airway pressure (CPAP) therapy exist but are restricted to a small case series rather than controlled trials.
Overall, clinical evidence is preliminary and insufficient to establish causality or to quantify the effect size of OSA on wound outcomes across patient populations.
Given the global prevalence and underdiagnosis of OSA, the condition could represent an overlooked and potentially modifiable contributor to impaired wound healing. The review highlights several implications:
Clinicians managing chronic wounds—particularly diabetic foot ulcers—should be aware of OSA as a possible comorbidity that might influence healing, although robust clinical guidance is not yet established.
There is a need for more comprehensive preclinical models, including in vivo studies, to better characterize IH effects on the complex multicellular processes of wound repair.
Controlled clinical studies, ideally randomized and with objective OSA assessment and standardized wound outcomes, are required to determine whether treating OSA (for example with CPAP) improves wound healing.
The review concludes that OSA, through intermittent hypoxia and associated systemic effects, is biologically plausible as a contributor to impaired skin wound healing. However, both preclinical and clinical evidence remain limited and heterogeneous. Key knowledge gaps include the scarcity of animal and translational studies, the lack of robust controlled clinical trials, and uncertainty about the magnitude and mechanisms of any causal relationship. The authors suggest that OSA may be an overlooked, potentially modifiable factor in wound care, but emphasize the need for additional research to inform clinical practice.