Dissemond J. Ulcus Cruris - Genese, Diagnostik und Therapie. 4. Aufl.Bremen: Uni-med; 2012

Protz K. Moderne Wundversorgung. 6. Aufl.Amsterdam: Elsevier; 2011

Gordillo G.M., Sen C.K. Revisiting the essential role of oxygen in wound healing. Am J Surg. 2003; 186:(3)259-263

Schreml S., Szeimies R.M., Prantl L. Oxygen in acute and chronic wound healing. Br J Dermatol. 2010; 163:(2)257-268

Bollinger A., Hoffmann U., Franzeck U.K. Microvascular changes in arterial occlusive disease: Target for pharmacotherapy. Vasc Med. 1996; 1:(1)50-54

Becker F., Robert-Ebadi H., Ricco J.B. Chapter I: Definitions, epidemiology, clinical presentation and prognosis. Eur J Vasc Endovasc Surg. 2011; 42:S4-12

Greenman R.L., Panasyuk S., Wang X. Early changes in the skin microcirculation and muscle metabolism of the diabetic foot. Lancet. 2005; 366:(9498)

Jörneskog G., Brismar K., Fagrell B. Skin capillary circulation is more impaired in the toes of diabetic than non-diabetic patients with vascular disease. Diabet Med. 1995; 12:(1)36-41

Tooke J.E., Brash P.D. Microvascular aspects of diabetic foot disease. Diabet Med. 1996; 13:26-29

Ropper A. H., Samuels M.A. Adams and Victor's Principles of Neurology, 9th edn. : McGraw-Hill Company; 2009

Hile C., Veves A. Diabetic neuropathy and microcirculation. Curr Diab Reports. 2003; 3:(6)446-451

Pham H.T., Economides P.A., Veves A. The role of endothelial function on the foot - microcirculation and wound healing in patients with diabetes. Clin Podiatr Med Surg. 1998; 15:(1)85-93

Veves A., Akbari C.M., Primavera J. Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration. Diabetes. 1998; 47:(3)457-463

Barnikol W.K., Pötzschke H. [A novel, non-invasive diagnostic clinical procedure for the determination of an oxygenation status of chronic lower leg ulcers using peri-ulceral transcutaneous oxygen partial pressure measurements: results of its application in chronic venous insufficiency (CVI)]. Ger Med Sci. 2012; 10

Malone P.C., Agutter P.S. To what extent might deep venous thrombosis and chronic venous insufficiency share a common etiology?. Int Angiol. 2009; 28:(4)254-268

Moysidis T. [Venous ulcer is an ischemic wound!]. MMW Fortschr Med. 2012; 154:73-76

Jünger M., Hahn M., Klyscz T., Steins A. Microangiopathy in the pathogenesis of chronic venous insufficiency. In: Hafner J., Ramelet A.A., Schmeller W., Brunner U.V. (eds). : Karger; 1999

Jünger M., Klyscz T., Hahn M., Schiek A. Mikroangiopathie der Haut bei chronischer Ischämie. Phlebologie. 1993; 22:86-90

Franzeck U.K., Bollinger A., Huch R., Huch A. Transcutaneous oxygen tension and capillary morphology characteristics and density in patients with chronic venous incompetence. Circulation. 1984; 70:(5)806-811

Jünger M., Steins A., Hahn M., Häfner H.M. Microcirculatory dysfunction in chronic venous insufficiency (CVI). Microcirculation. 2000; 7:(6 Pt 2)3-12

Mani R., Gorman W., White J,E. Transcutaneous measurements of oxygen tension at edges of leg ulcers: Preliminary communication. J R Soc Med. 1986; 79:(11)650-654

Stücker M., Schöbe M.C., Hoffmann K., Schultz-Ehrenburg U. Cutaneous microcirculation in skin lesions associated with chronic venous insufficiency. Dermatol Surg. 1995; 21:(10)877-882

Beckert S., Küper M., Königsrainer A. Sauerstoff und Wundheilung ZfW. 2008; 4:232-238

Bishop A. Role of oxygen in wound healing. J Wound Care. 2008; 17:(9)399-402

Hopf H.W., Rollins M.D. Wounds: an overview of the role of oxygen. Antioxid Redox Signal. 2007; 9:(8)1183-1192

Rodriguez P.G., Felix F.N., Woodley D.T., Shim E.K. The role of oxygen in wound healing - A review of the literature. Dermatol Surg. 2008; 34:(9)1159-1169

Sen C.K. Wound Healing Essentials: Let there be oxygen. Wound Repair Regen. 2009; 17:(1)1-18

Fife C.E., Smart D.R., Sheffield P.J. Transcutaneous oximetry in clinical practice: consensus statements from an expert panel based on evidence. Undersea Hyperb Med. 2009; 36:(1)43-53

Figoni S.F., Scremin O.U., Kunkel C.F. Preamputation evaluation of limb perfusion with laser Doppler imaging and transcutaneous gases. J Rehabil Res Dev. 2006; 43:(7)891-904

Tandara A.A., Mustoe T.A. Oxygen in wound healing - more than a nutrient. World J Surg. 2004; 28:(3)294-300

Gupta A., Raghubir R. Energy metabolism in the granulation tissue of diabetic rats during cutaneous wound healing. Mol Cell Biochem. 2005; 270:1-2

Hopf H.W., Hunt T.K., West J.M. Wound tissue oxygen tension predicts the risk of wound infection in surgical patients. Arch Surg. 1997; 132:(9)997-1005

Babior B.M. Oxygen dependent microbial killing by phagocytes. N Engl J Med. 1978; 298:(12)658-668

Allen D.B., Maguire J.J., Mahdavian M. Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg. 1997; 132:(9)991-996

Coleman M.L., Ratcliffe P.J. Oxygen sensing and hypoxia-induced responses. Essays Biochem. 2007; (43)1-15

Wiesener M.S., Maxwell P.H. HIF and oxygen sensing: As important to life as the air we breathe?. Ann Med. 2003; 35:(3)183-190

Werner S., Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003; 83:(3)835-870

Cockbill S. Wounds The healing process. Hosp Pharmacist. 2002; 9:255-260

Singer A.J., Clark R.A. Cutaneous wound healing. N Engl J Med. 1999; 341:(10)738-746

Fu M.X., Knecht K.J., Thorpe S.R., Baynes J.W. Role of oxygen in cross-linking and chemical modification of collagen by glucose. Diabetes. 1992; 41:42-48

Robins S.P. Biochemistry and functional significance of collagen crosslinking. Biochem Soc Trans. 2007; 35:(pt5)849-852

Johnstone C.C., Farley A. The physiological basics of wound healing. Nurs Stand. 2005; 19:(43)59-65

Gordillo G.M., Sen C.K. Evidence-based recommendations for the use of topical oxygen therapy in the treatment of lower extremity wounds. Int J Low Extrem Wounds. 2009; 8:(2)105-111

Tawfick W.A., Sultan S. Technical and clinical outcome of topical wound oxygen in comparison to conventional compression dressings in the management of refractory nonhealing venous ulcers. Vasc Endovascular Surg. 2013; 47:(1)30-37

Davis S.C., Cazzaniga A.L., Ricotti C. Topical oxygen emulsion: a novel wound therapy. Arch Dermatol. 2007; 143:(10)1252-1256

Banks P.G., Ho C.H. A novel topical oxygen treatment for chronic and difficult-to-heal wounds: case studies. J Spinal Cord Med. 2008; 31:(3)297-301

Arenbergerova M., Engels P., Gkalpakiotis S. Einfluss von topischem Hämoglobin auf die Heilung von Patienten mit Ulcus cruris venosum. [Topical hemoglobin promotes healing of patients with venous leg ulcers]. Hautarzt. 2013; 64:(3)180-186

Stücker M., Struk A., Altmeyer P. he cutaneous uptake of atmospheric oxygen contributes significantly to the oxygen supply of human dermis and epidermis. J Physiol. 2002; 538:(pt3)985-994

Tromans D. Temperature and pressure dependent solubility of oxygen in water: a thermodynamic analysis. Hydrometallurgy. 1998; 48:(3)327-342

Darrington R.S., Godden D.J., Park M.S. The effect of hyperoxia on expression of cytokine mRNA in endothelial cells. Biochem Soc Trans. 1997; 25:(2)

Deaton P.R., McKellar C.T., Culbreth R. Hyperoxia stimulates interleukin-8 release from alveolar macrophages and U937 cells: attenuation by dexamethasone. Am J Physiol. 1994; 267:(2 pt 1)187-192

Maniscaloca W.M., Watkins R.H., Finkelstein J.N., Campbell M.H. Vascular endothelial growth factor mRNA increases in alveolar epithelial cells during recovery from oxygen injury. Am J Respir Cell Mol Biol. 1995; 13:(4)377-386

Gordillo G.M., Roy S., Khanna S. Topical oxygen therapy induces vascular endothelial growth factor expression and improves closure of clinically presented chronic wounds. Clin Exp Pharmacol Physiol. 2008; 35:(8)957-964

Feldmeier J.J., Hopf H.W., Warriner R.A. UHMS position statement: topical oxygen for chronic wounds. Undersea Hyperb Med. 2005; 32:(3)157-168

Blackman E., Moore C., Hyatt J. Topical wound oxygen therapy in the treatment of severe diabetic foot ulcers: A prospective controlled study. Ostomy Wound Manag. 2010; 56:(6)24-31

Fisher B.H. Topical hyperbaric oxygen treatment of pressure sores and skin ulcers. Lancet. 1969; 2:(7617)405-409

Kalliainen L.K., Gordillo G.M., Schlanger R., Sen C.K. Topical oxygen as an adjunct to wound healing: a clinical case series. Pathophysiology. 2003; 9:(2)81-87

Fries R.B., Wallace W.A., Roy S. Dermal excisional wound healing in pigs following treatment with topically applied pure oxygen. Mutat Res. 2005; 579:1-2

Said H.K., Hijjawi J., Roy N. Transdermal sustained-delivery oxygen improves epithelial healing in a rabbit ear wound model. Arch Surg. 2005; 140:(10)998-1004

Hirsh F., Berlin S.J., Holtz A. Transdermal oxygen delivery to diabetic wounds: A report of 6 cases. Adv Skin Wound Care. 2009; 22:(1)20-24

Lowell D., Nicklas B,., Welly W. Transdermal continuous oxygen therapy as an adjunct for treatment of recalcitrant and painful wounds. Foot Ankle Online J. 2009; 2:(9)

Woo K.Y., Coutts P.M., Sibbald R.G. Continuous topical oxygen for the treatment of chronic wounds: a pilot study. Adv Skin Wound Care. 2012; 25:(12)543-547

Kemp D.G., Hermans M.H.E. An evaluation of the efficacy of transdermal continuous oxygen therapy in patients with recalcitrant diabetic foot ulcer. J Diabetic Foot Complications. 2011; 3:(1)6-12

Lo J.F., Brennan M., Merchant Z. LA. Microfluidic wound bandage: localized oxygen modulation of collagen maturation. Wound Repair Regen. 2013; 21:(2)226-234

Lairet K.F., Baer D., Leas M.L. Evaluation of an oxygen-diffusion dressing for accelerated healing of donor-site wounds. J Burn Care Res. 2014; 35:(3)214-218

Ivins N., Simmonds W., Turner A., Harding K. The use of an oxygenating hydrogel dressing in VLU. Wounds UK. 2007; 3:77-81

Davis P., Wood L., Wood Z. Clinical experience with a glucoseoxidase-containing dressing on recalcitrant wounds. J Wound Care. 2009; 18:(3)114-121

Barnikol W.K.R., Teslenko A., Pötzschke H. Eine neue topische Behandlung chronischer Wunden mit Hämoglobin und Sauerstoff: Verfahren und erste Ergebnisse. ZfW. 2005; 13:(3)98-108

Scholander P.F. Oxygen transport through hemoglobin solutions. Science. 1960; 131:(3400)585-590

Page T.C., Light W.R., McKay C.B., Hellums J.D. Oxygen transport by erythrocyte/hemoglobin solution mixtures in an in vitro capillary as a model of hemoglobin-based oxygen carrier performance. Microvasc Res. 1998; 55:(1)54-64

Arenberger P., Engels P., Arenbergerova M. Clinical results of the application of a hemoglobin spray to promote healing of chronic wounds. GMS Krankenhaushyg Interdiszip. 2011; 6:(1)

Norris R. A topical haemoglobin spray for oxygenating chronic venous leg ulcers: a pilot study. Br J Nurs. 2014; 23:S48-53

Babadagi-Hardt Z., Engels P., Kanya S. Wound management with compression therapy and topical hemoglobin solution in a patient with Budd-Chiari Syndrome. J Dermatol Case Rep. 2014; 8:(1)20-23

Barnikol W.K., Pötzschke H. [Complete healing of chronic wounds of a lower leg with haemoglobin spray and regeneration of an accompanying severe dermatoliposclerosis with intermittent normobaric oxygen inhalation (INBOI): a case report]. Ger Med Sci. 2011; 30:(9)

Riess J.G., Krafft M.P. Fluorinated materials for in vivo oxygen transport (blood substitutes), diagnosis and drug delivery. Biomaterials. 1998; 19:(16)1529-1539

Wijekoon A., Fountas-Davis N, Leipzig N.D. Fluorinated methacrylamide chitosan hydrogel systems as adaptable oxygen carriers for wound healing. Acta Biomater. 2013; 9:(3)5653-5664

Topical oxygen wound therapies for chronic wounds: a review

02 July 2019
Volume 3 · Issue 3


Chronic wounds are an increasing problem in our ageing population and can arise in many different ways. Over the past decades it has become evident that sufficient oxygen supply is an essential factor of appropriate wound healing. Sustained oxygen deficit has a detrimental impact on wound healing, especially for patients with chronic wounds. This has been proven for wounds associated with peripheral arterial occlusive disease (PAOD) and diabetic foot ulcers (particularly in combination with PAOD). However, this is still under debate for other primary diseases.

In the past few years several different new therapeutic approaches for topical oxygen therapies have been developed to support wound healing. These tend to fall into one of four categories: (1) delivery of pure oxygen either under pressurised or (2) ambient condition, (3) chemical release of oxygen via an enzymatic reaction or (4) increase of oxygen by facilitated diffusion using oxygen binding and releasing molecules. In this review article, the available therapeutic topical oxygen-delivering approaches and their impact on wound healing are presented and critically discussed. A summary of clinical data, daily treatment recommendations and practicability is provided.

The most common chronic wounds are leg ulcers, foot ulcers and pressure ulcers (PU).1,2 In most cases, patients with such wounds suffer from peripheral arterial occlusive disease (PAOD), chronic venous insufficiency (CVI) and/or diabetes mellitus, or, in the case of PUs, immobility. It is generally accepted that, in PAOD and diabetic foot syndrome, a disturbance in the vascular system results in a sustained inadequate supply of oxygen and finally chronic hypoxia. These conditions dramatically increase the probability of developing a chronic wound.3,4 In patients with PAOD, the relationship between oxygen deficiency and reduced arterial perfusion has been well known for decades.5 Depending on the degree of the reduction, the hypoxia reaches a critical threshold below which wound healing is significantly decreased. This stage of PAOD is termed chronic critical ischaemia.6

Register now to continue reading

Thank you for visiting Wound Central and reading some of our peer-reviewed resources for wound care professionals. To read more, please register today. You’ll enjoy the following great benefits:

What's included

  • Access to clinical or professional articles

  • New content and clinical updates each month