Oxygen in Acute and Chronic Wound Healing

S. Schreml; R.M. Szeimies; L. Prantl; S. Karrer; M. Landthaler; P. Babilas

Disclosures

The British Journal of Dermatology. 2010;163(2):257-268. 

In This Article

Abstract and Introduction

Abstract

Oxygen is a prerequisite for successful wound healing due to the increased demand for reparative processes such as cell proliferation, bacterial defence, angiogenesis and collagen synthesis. Even though the role of oxygen in wound healing is not yet completely understood, many experimental and clinical observations have shown wound healing to be impaired under hypoxia. This article provides an overview on the role of oxygen in wound healing and chronic wound pathogenesis, a brief insight into systemic and topical oxygen treatment, and a discussion of the role of wound tissue oximetry. Thus, the aim is to improve the understanding of the role of oxygen in wound healing and to advance our management of wound patients.

Introduction

An injury to the skin may disturb the integrity of the epidermis, the dermis, the connective tissue and the microcirculation, and thus inevitably results in a wound. The disturbed equilibrium of the local environment induces wound healing.[1] Physiological wound healing is a well-regulated stepwise process that ends with wound closure within days or weeks, depending on diameter and depth of the wound.[2,3] One critical parameter for wound healing is oxygen that is required for almost every step of the healing process.[4–7] The oxygenation of wound tissue is dependent on both the oxygen supply to the wound tissue – that is determined by the pulmonic gas exchange, the blood haemoglobin level, the cardiac output, the peripheral perfusion rate, and by the capillary density in the wound tissue and its periphery – and on the oxygen consumption rate of parenchymal, stromal and inflammatory cells of which the wound tissue is composed. Interestingly, in literature dealing with wound tissue oxygenation, the unit mmHg for oxygen partial pressure (pO2) is still widely used even though it is not the standard SI unit, which is pascal (1 Pa = 7·5006 × 10−3 mmHg). Therefore, we use mmHg throughout this review to make it easier for the reader to compare data from the different publications cited herein.

In wound healing, biochemical energy supply is a basic requirement. Oxygen is essential for the production of biological energy equivalents (e.g. adenosine triphosphate, ATP) in aerobic glycolysis, the citric acid cycle, and the oxidation of fatty acids.[4,7] Therefore, sufficient oxygenation of tissue is a prerequisite for adequate energy levels, which are essential for proper cellular function.

In healing tissue, sufficient oxygenation is particularly relevant because of the increased energy demand for reparative processes such as cell proliferation, bacterial defence and collagen synthesis. The strictly oxygen-dependent NADPH-linked oxygenase represents a further highly important enzyme in wound healing; it catalyses the production of reactive oxygen species (ROS) such as peroxide anion (HO2), hydroxyl ion (HO) and superoxide anion (O2−).[8] ROS play a prominent role in oxidative bacterial killing[9,10] and coregulate prevalent processes in wound healing such as cytokine release, cell proliferation and angiogenesis.[8,11]

Against this background, the crucial role of reduced oxygen supply in chronic wound pathogenesis becomes obvious. Chronic wounds are characterized by an insufficient repair process that precludes the establishment of a sustained anatomical and functional result in an appropriate length of time.[1,2] Chronic wounds represent a frequent interdisciplinary disease affecting about 1% of the European population. According to the United Nations (see http://www.un.org/), the population of Europe was approximately 830 million in 2009, using a definition including the whole of the transcontinental countries of Russia and Turkey. Based on these figures, about 8 million people in Europe suffered from chronic wounds in 2009. Besides the tremendous impact on the quality of life of the affected patients, chronic wounds are of fundamental economic relevance: nearly 2% of European health budgets are spent on the impaired healing of chronic wounds.[12,13] In Germany, over 2·8 million sick days per year are caused by chronic wounds. In the U.S.A., approximately one-third of the dermatological health budget is spent on the treatment of chronic wounds.[14]

This review summarizes the role of oxygen in the sequential steps of physiological wound healing. The pathogenesis of chronic wounds is explained against the background of impaired wound tissue oxygenation. Moreover, we question the benefits of treatment strategies for improving wound tissue oxygenation and discuss the role of wound tissue oxygen measurement either to classify chronic wounds or to monitor different treatment approaches in clinical routine.

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