Wound healing essentials: Let there be oxygen

Abstract

The state of wound oxygenation is a key determinant of healing outcomes. From a diagnostic standpoint, measurements of wound oxygenation are commonly used to guide treatment planning such as amputation decision. In preventive applications, optimizing wound perfusion and providing supplemental O2 in the perioperative period reduces the incidence of postoperative infections. Correction of wound pO2 may, by itself, trigger some healing responses. Importantly, approaches to correct wound pO2 favorably influence outcomes of other therapies such as responsiveness to growth factors and acceptance of grafts. Chronic ischemic wounds are essentially hypoxic. Primarily based on the tumor literature, hypoxia is generally viewed as being angiogenic. This is true with the condition that hypoxia be acute and mild to modest in magnitude. Extreme near‐anoxic hypoxia, as commonly noted in problem wounds, is not compatible with tissue repair. Adequate wound tissue oxygenation is required but may not be sufficient to favorably influence healing outcomes. Success in wound care may be improved by a personalized health care approach. The key lies in our ability to specifically identify the key limitations of a given wound and in developing a multifaceted strategy to specifically address those limitations. In considering approaches to oxygenate the wound tissue it is important to recognize that both too little as well as too much may impede the healing process. Oxygen dosing based on the specific need of a wound therefore seems prudent. Therapeutic approaches targeting the oxygen sensing and redox signaling pathways are promising.

Critical Reviews: How we treat sickle cell patients with leg ulcers

“…Systemic antibiotics need to be used only sparingly, as most wounds are colonized by skin flora, and may have a thick biofilm, which does not respond to systemic therapy. While hypothetically the local wound area is ischemic and anecdotally some kind of oxygen delivery to the wound has been attempted [63], we and others have seen no sustained benefit from hyperbaric chamber treatment [64], which is cumbersome, and potentially risky in SCD as there have been anecdotal reports of adverse events caused by this treatment modality [65].…”

Dextran-shelled oxygen-loaded nanodroplets reestablish a normoxia-like pro-angiogenic phenotype and behavior in hypoxic human dermal microvascular endothelium

“…In particular, 91 during the third and fourth phases, the endothelium plays a pivotal role, since wound 92 microvasculature is rebuilt through angiogenesis to restore the supply of oxygen, blood 93 constituents and nutrients to the regenerating tissue, helping to promote fibroplasia and 94 prevent sustained tissue hypoxia [Eming et al, 2014]. Notably, oxygen represents a key 95 regulator of normal wound healing since it is required for collagen deposition, 96 epithelialization, fibroplasia, angiogenesis, and resistance to infection [Castilla et al, 2012; 97 Sen, 2009]. Once complete, these processes must be shut down in a precise order to prevent 98 exaggerated or delayed responses.…”

“…For this reason, the major role played by oxygen in essential wound healing 131 processes has attracted considerable clinical interest and yielded compelling data [Sen, 2009]. 132…”

“…So far, hyperbaric oxygen therapy remains a well-established, adjunctive treatment for 138 diabetic lower extremity wounds, when refractory to standard care practices [Sen, 2009]. 139…”

“…In a couple of recent works published by our group 122 hypoxia was shown to reduce MMP-9 and increase TIMP-1 without affecting TIMP-2 123 secretion by human monocytes [Gulino et al, 2015], whereas in human keratinocytes 124 hypoxia was shown to reduce MMP-2, MMP-9, and TIMP-2 secretion without changing 125 TIMP-1 levels and venous ulcers). Topical oxygen therapy, based on an O 2 gas emulsion applied to the 143 superficial wound tissue, represents another promising approach to enhance the oxygenation 144 of wounded tisues [Sen, 2009]. Major advantages of topical oxygen therapy appear to be its 145 independence of the wound microcirculation, its lower cost with respect to systemic oxygen 146 therapy, lower risks of oxygen toxicity, and its relative simplicity of handling and application.…”