Wound Healing and Hyperbaric Oxygen Therapy Physiology: Oxidative Damage and Antioxidant Imbalance
- mdavis107
- Nov 13, 2020
- 7 min read
Updated: 6 days ago
One of the key obstacles in chronic wound healing is the presence of tissue hypoperfusion, sustained hypoxia, and ongoing infection. These conditions create a wound environment that is hostile to normal tissue repair. Hyperbaric oxygen therapy (HBOT) has been shown to reverse some of these physiological barriers by delivering oxygen at pressures high enough to restore oxygen balance, reduce infection, and promote healing. The clinical efficacy of HBOT is well-documented, especially in treating hypoxic wounds that fail to respond to conventional treatment. [1]
The Role of Oxygen in Healing
Adequate molecular oxygen is required for a wide range of biosynthetic processes essential to normal healing. Molecular oxygen is required for hydroxylation of proline during collagen synthesis and cross linking as well as provision of substrate for the production of reactive oxygen species during the respiratory burst occurring within leukocytes that phagocytize bacteria. While short-term hypoxia is one stimulus for angiogenesis in wound healing, adequate local oxygen levels are required to sustain an effective angiogenic response and for the reconstruction of the dermal matrix. Recent research has shown that oxygen also plays an important role in cell signaling events necessary for tissue repair, which further explains the fragile dynamic between oxygen availability and increased demands for oxygen during wound healing.2

Hyperbaric Oxygen Therapy: How It Works and Why It Matters
Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen at pressures typically ranging from 2.0 to 3.0 atmospheres absolute (ATA), dramatically increasing the amount of oxygen that dissolves directly into the plasma. While hemoglobin usually carries most of the body’s oxygen, its capacity is limited by chemical binding. In contrast, plasma-dissolved oxygen—guided by Henry’s Law—increases proportionally with pressure and can rise to over 2,200 mmHg at 3.0 ATA. In fact, studies dating back to 1960 demonstrated that life could be sustained in animals without red blood cells, relying solely on this oxygen-rich plasma. [5]

Hyperbaric chambers can raise tissue oxygen levels (PO₂) above 1,700 mmHg.[3,4] This high-pressure environment enables oxygen to reach tissues with compromised blood supply, extending its diffusion distance from capillaries and delivering it deep into hypoxic or inflamed areas—something not possible under normal conditions.
When breathing 100% oxygen at 2 ATA, plasma oxygen levels rise from a baseline of just 0.3 ml/100 ml of blood to over 4.4 ml. At 3 ATA, this rises to 6.4 ml/100 ml—enough to meet resting oxygen demand even without red blood cells.
Why Increased Oxygen Diffusion Matters for Wound Healing
By increasing the amount and depth of oxygen diffusion, HBOT helps overcome one of the major barriers in chronic wound care: hypoxia. Clinical studies and physiological models have shown that raising plasma oxygen concentration significantly boosts:
Tissue oxygenation, which supports cellular energy production and healing.
Collagen synthesis and extracellular matrix formation, key to tissue repair.
Leukocyte function, enhancing bacterial killing and modulating inflammation.
Antibiotic effectiveness, as many antimicrobial agents require oxygen for cellular uptake.
Reduction in edema, through vasoconstriction in non-ischemic tissues.
HBOT’s Role in Modulating Oxidative Stress and Cell Signaling
Modern research also highlights HBOT’s role in regulating reactive oxygen species (ROS) and reactive nitrogen species (RNS)—molecules that act as cellular signals but can cause tissue damage when unregulated. HBOT, when administered within safety limits (≤3 ATA), helps modulate these signals to:
Promote angiogenesis through VEGF and PDGF activation.
Reduce inflammation and apoptosis in ischemic wound models.
Enhance stem cell release and activity.
Improve integrin receptor sensitivity, crucial in ischemia-reperfusion injury recovery.
While high oxygen levels can lead to toxicity if not carefully controlled, standard clinical HBOT protocols are designed to stay well below neurologic or pulmonary risk thresholds.
Tissue Effects of HBOT
HBOT impacts wound physiology through several short-term mechanisms:
- Increases tissue oxygenation and ATP production.
- Enhances collagen formation and epithelialization.
- Reduces edema by inducing vasoconstriction.
- Boosts immune cell function and improves antibiotic efficacy.
Long-term, HBOT alters the wound’s microenvironment by modulating reactive oxygen species (ROS) and reactive nitrogen species (RNS), reducing inflammation, improving angiogenesis, and activating stem cell mobilization. [7][8][9][10][11][12]
Oxygen Toxicity and Safety
Although oxygen is essential, it can also be toxic at high concentrations. Excessive ROS from HBOT may lead to neurological or pulmonary toxicity if administered without proper safety parameters. That's why treatment protocols typically limit exposure to 2.0–2.5 ATA. [3]
Why Chronic Wounds Stay Stuck
Acute wound healing is a highly organized, efficient process that progresses through four overlapping phases: hemostasis, inflammation, proliferation, and remodeling. In contrast, chronic wounds often fail to initiate this process correctly. When the hemostasis phase is absent or disrupted, the wound becomes locked in a prolonged inflammatory state—one marked by excessive neutrophil infiltration, reactive oxygen species (ROS), and tissue-damaging enzymes.
This dysfunctional wound environment becomes self-sustaining, preventing progression to later stages of healing. Only by restoring microenvironmental balance—reducing inflammation and oxidative stress—can the wound begin to heal.
Chronic wounds typically result from persistent inflammatory triggers such as repetitive trauma, localized ischemia, or low-grade bacterial contamination. These stimuli activate immune responses and lead to the release of proinflammatory cytokines—like TNF-α and IL-1β—that drive further tissue degradation and delay healing. [16]
The Chronic Wound Microenvironment
Chronic wounds are stuck in an extended inflammatory phase and characterized by high protease activity (MMPs), excessive ROS, and deficient protease inhibitors (TIMPs). This imbalance breaks down extracellular matrix proteins and growth factor receptors, delaying healing and fostering cellular senescence. [16][17][18][19]
Pain, Hypoxia, and Metabolic Disruption
As chronic wounds persist in a hypoxic state, they shift toward anaerobic metabolism, increasing lactate production and lowering pH levels. This metabolic acidosis can trigger pain via nociceptor stimulation. In contrast, aerobic metabolism enabled by HBOT alleviates these symptoms. [20][21][22]
Conclusion
HBOT represents a unique therapeutic modality that addresses both the metabolic and inflammatory barriers in chronic wound healing. By enhancing oxygen availability, supporting cellular function, and restoring microenvironmental balance, HBOT helps wounds progress from chronic inflammation to active repair.
At Shared Health Services, we support hospitals and physician practices through expert implementation of advanced wound care and hyperbaric medicine programs. As a trusted wound care management company, we work alongside your team to evaluate, improve, or expand your wound care services—whether that means bringing operations in-house, transitioning from another vendor, or launching a new wound care center tailored to your facility's needs.
References
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