Associate Professor Plastic Surgery
The Ohio State University
Any clinician would agree that oxygen is required for wound healing as ischemic wounds do not heal. Those wounded body parts that do not receive adequate oxygenation progress to amputation or removal. Venous leg ulcers and diabetic foot ulcers are the most common chronic wounds. For many of these patients oxygen delivery is compromised or fails to achieve the necessary levels of tissue oxygenation required for optimal function of biologic mediators of the wound healing response. For example, the enzymes required for bacterial killing require oxygen levels (pO2) of 45-80 mmHg for half maximal function and >300 mmHg for maximal function. Additionally, the amount of oxygen needed for the collagen synthesis enzyme prolyl hydroxylase to achieve half maximal function is 25 mmHg and maximal function is at 250 mmHg.1 These levels of oxygenation are not found under physiologic conditions in the vast majority of patients, especially those with lower extremity wounds.
Our group has the only published data demonstrating that topical oxygen therapy can diffuse across the wound bed to increase wound tissue oxygen tension.2 Using this same method of topical oxygen delivery on an intermittent basis, we have shown that it can increase wound tissue expression of Vascular Endothelial Growth Factor, stimulate new blood vessel formation in wound tissue resulting in sustained levels of increased wound tissue pO2, and promote wound closure.2, 3 These are measurable clinical endpoints that are known to support the wound healing process. Our collaborators have also shown that cells sense relative changes in oxygen tension and respond by altering protein activation, e.g. prolyl hydroxylase domain enzymes, and microRNA expression to effect long term biologic changes after oxygen exposure has ceased.4-6
Our group has also published the largest retrospective case series on topical oxygen therapy delivered for 90 minutes 4 times per week and found that all subjects responded positively with a decrease in wound size regardless of wound chronicity with no adverse events. Patients treated with topical oxygen therapy had healing rates similar to those obtained among patients receiving care in a specialized wound clinic.7 All patients treated with topical oxygen therapy were included and no inclusion or exclusion criteria applied in the decision to use the therapy resulting in a highly pragmatic assessment of results.
In summary, there is a clear mechanistic rationale and sufficient evidence from human subjects and experimental models to support the use of topical oxygen therapy administered on an intermittent basis. Regardless of the mechanism of topical oxygen administration, patients would benefit from access to oxygen therapy that can be used in their own home.
Gayle Gordillo, MD, FACS
Associate Professor of Plastic Surgery, Medical Director of Wound Services
Richard Schlanger, MD, PhD
Professor of Surgery -Clinical
The Ohio State University
1.Gordillo GM, Sen CK. Revisiting the essential role of oxygen in wound healing. Am J Surg. 2003;186:259-263
2.Fries RB, Wallace WA, Roy S, Kuppusamy P, Bergdall V, Gordillo GM, Melvin WS, Sen CK. Dermal excisional wound healing in pigs following treatment with topically applied pure oxygen. Mutat Res. 2005;579:172-181
3.Gordillo GM, Roy S, Khanna S, Schlanger R, Khandelwal S, Phillips G, Sen CK. Topical oxygen therapy induces vascular endothelial growth factor expression and improves closure of clinically presented chronic wounds. Clin Exp Pharmacol Physiol. 2008;35:957-964
4.Sen CK. Wound healing essentials: Let there be oxygen. Wound Repair Regen. 2009;17:1-18
5.Sen CK, Roy S. Oxygenation state as a driver of myofibroblast differentiation and wound contraction: Hypoxia impairs wound closure. J Invest Dermatol. 2010;130:2701-2703
6.Sen CK, Roy S. Oxymirs in cutaneous development, wound repair and regeneration. Semin Cell Dev Biol. 2012;23:971-980
7.Kalliainen LK, Gordillo GM, Schlanger R, Sen CK. Topical oxygen as an adjunct to wound healing: A clinical case series. Pathophysiology. 2003;9:81-87