Publication:

From oxygen biology to surgical outcomes: translating hyperbaric oxygen therapy mechanisms into tissue salvage

Hyperbaric oxygen therapy (HBOT) has emerged as a valuable adjunct in the management of ischemic and complex surgical wounds; however, its clinical application remains heterogeneous and often empirically driven. Despite growing evidence supporting its efficacy, a critical gap persists between the mechanistic understanding of HBOT and its integration into surgical decision-making. This systematic review aimed to synthesize current evidence on the biological mechanisms underlying HBOT and translate these mechanisms into clinically relevant outcomes. A structured search of PubMed/MEDLINE, Scopus, and Web of Science identified 312 records, of which 30 studies were included in the final qualitative synthesis. The evidence identified enhanced oxygen diffusion, angiogenesis and neovascularization, inflammatory modulation, antimicrobial activity, and cellular regeneration as interconnected mechanisms underlying the therapeutic effects of HBOT. Across surgical contexts, these mechanisms were associated with improved wound healing, enhanced tissue viability, infection control, reduced tissue necrosis, and lower amputation risk in selected clinical settings. Considerable heterogeneity was identified in treatment timing, pressure, session duration, frequency, and total number of sessions, with therapeutic responsiveness appearing to depend on the underlying pathophysiology, stage of tissue injury, and residual tissue viability. Based on these findings, a translational framework linking tissue hypoxia, ischemia, inflammation, infection, and impaired regeneration with specific HBOT-mediated mechanisms and expected clinical outcomes is proposed. Collectively, the findings support conceptualizing HBOT as a targeted adjunctive therapy rather than a universally applicable intervention, emphasizing mechanism-driven patient selection, appropriate treatment timing, and individualized therapeutic strategies to optimize its role in surgical tissue salvage and wound healing.