New Insights Into Oxygen Therapy for Wound Healing

Daniel Ladizinsky, MD; David Roe, PhD


Wounds. 2010;22(12):294-300. 

In This Article

Topical Oxygen Therapy and its Efficacy: Gaseous vs. Dissolved

Many wound patients cannot tolerate systemic HBOT side effects, afford HBOT, or gain access to a hyperbaric chamber. Sometimes the patient's cardiovascular system is inadequate for carrying the oxygenated blood to the wounded tissue, or the tissue is so edematous that the oxygen cannot reach the wound well. Topical oxygen therapies are designed to allow oxygen to enter the wound or skin via the external surface of the body rather than from capillaries within. The oxygen is therefore delivered directly to the wound and the systemic side effects are eliminated.

Topical oxygen therapy may be delivered to the external surfaces of the body in a gaseous or dissolved form. However, the administered oxygen must be transformed from the gaseous to the dissolved form to become biologically available to the target cells being treated.

Topical gaseous "oxygen boot" systems have been proposed since 1932 with refinements since. Treatment methods that deliver gaseous oxygen include enclosures around a limb or wound site that are flushed with pure gaseous oxygen, or machines that generate gaseous oxygen at the wound surface.[33] A recent review discusses the evidence based recommendations for topical oxygen therapy.[34]

For oxygen to be transferred from a gas bubble to an individual cell, several independent partial resistances must be overcome including:[35]

  • resistance within the gas film to the phase boundary

  • penetration of the phase boundary between gas bubble and liquid

  • transfer from the phase boundary to the liquid

  • movement within the nutrient solution

  • transfer to the surface of the cell.

These intrinsic issues limit the efficacy of gaseous topical oxygen systems; yet, topical low-pressure oxygen therapy has shown some encouraging results in preliminary studies. One hundred percent oxygen is administered at atmospheric or slightly greater pressure without a hyperbaric chamber via an enclosure that surrounds the affected area. It is inexpensive and can be provided in the home environment. It has been shown to promote wound angiogenesis and healing in animal studies as well as in human clinical studies.[36–38] A topical device that administers a stream of 100% oxygen bubbles to the wound surface has been shown to improve epithelial healing.[39]

Methods that deliver topical dissolved oxygen include those which catalytically produce dissolved oxygen at the wound surface, those which contain diffusible dissolved oxygen bound to a carrier such as a fluorocarbon, or those which allow a reservoir of gaseous oxygen to diffuse through the vehicle. There have been difficulties reported in creating stable fluorocarbon emulsions, however some promising early results have been reported.

Recent experimental data on a set of devices that deliver unbound dissolved oxygen have demonstrated significant oxygen penetration through viable human skin samples.[40] Levels of transcutaneous oxygen 4–6 times normal subcutaneous oxygen (250 mmHg) were observed after topical dissolved oxygen treatment of skin samples with or without a stratum corneum epidermal layer present. This level of penetration achieved was twice the depth of that noted in previous studies of skin exposed to hyperbaric gaseous oxygen.[20] Another recent study demonstrated penetration of topical dissolved oxygen through both intact (with epidermis) and tape striped (epidermis removed) viable porcine skin samples.[24]

There appears to be a significant advantage to delivering oxygen topically in its dissolved form, as it is biologically available immediately upon administration. The fundamental challenge to topical oxygenation methods is to create a large enough driving oxygen gradient to allow oxygen delivery into zones of tissue hypoxia. If this can be achieved clinically, topical tissue oxygenation procedures will become complementary to systemic methods of oxygenation and will allow the treating physician greater therapeutic versatility in treating wounds.

The ability to control duration and depth of topical oxygen delivery into human tissue will allow new strategies in individualizing patient therapy. A deeper understanding into the pharmacokinetics of topical oxygen administration will allow manipulation of specific healing processes (Table 2). Targeted oxygen therapies will be based on pharmacokinetics that will control oxygen tissue penetration depth, with degree and duration of oxygenation. New insights into oxygen's ability to penetrate intact skin may prove therapeutic in other conditions besides wounds, where inflammatory or degenerative conditions of the skin require repair and rejuvenation.