Hyperbaric Oxygen Therapy in Modern Surgical Practice: Mechanistic Basis and Clinical Applications Across Specialties

Post-surgical wound complications remain a major driver of morbidity and cost, largely mediated by tissue hypoxia, dysregulated inflammation, and infection. Hyperbaric oxygen therapy (HBOT) increases dissolved plasma oxygen and creates a transient hyperoxic milieu that supports fibroblast activity, collagen cross-linking, angiogenesis, and host antimicrobial defenses. We performed a targeted narrative review of PubMed/MEDLINE (January 2020-November 2025); 89 articles were identified, and 38 met the inclusion criteria. Mechanistic evidence shows HBOT modulates redox signaling, downregulates pro-inflammatory pathways, optimizes hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) dynamics, and balances matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) activity, thereby improving matrix quality and microvascular integrity. Clinically, across diabetic and vascular indications (diabetic foot ulcer, chronic limb-threatening ischemia, and venous/ischemic ulcers), adjunctive HBOT trends toward higher healing rates, improved limb preservation, and better graft take when added to standard care. In reconstructive and plastic surgery, HBOT supports threatened flaps and grafts and benefits burn management; aesthetic procedures show fewer complications and faster recovery. In trauma and orthopedic settings, early HBOT mitigates ischemia-reperfusion injury and aids soft-tissue salvage, while in oncologic/radiation contexts, it improves outcomes in late radiation tissue injury and irradiated reconstructive fields. Safety is favorable when typical regimens are used (2.0-2.5 ATA for 60-90 minutes, 20-40 sessions), with mostly mild, reversible adverse events. Evidence interpretation is limited by heterogeneity in protocols, endpoints, and patient selection. Future priorities include multicenter randomized trials, protocol standardization, biomarker-guided patient selection, and cost-effectiveness analyses. Overall, HBOT is a physiologically sound, clinically versatile perioperative adjunct that, when integrated into multidisciplinary pathways, can enhance healing and reduce complications across surgical specialties.