The Presence of Oxygen in Wound Healing

Howard M. Kimmel, DPM, MBA; Anthony Grant, DPM; James Ditata, BSN, RN, CNOR


Wounds. 2016;28(8):264-270. 

In This Article

Oxygen Sensing

Throughout the phases of wound healing there is a control of oxygen maintained in a narrow range. This point of normoxia is important because it is used to prevent abnormal periods of hypoxia or hyperoxia which can create damage to cell membranes.[5] This point of normoxia is the state of oxygenation where the cell or tissue does not report hypoxia nor does it report hyperoxia which would be oxygen toxicity.[47] If there were a change, the cells or tissue would react by switching on either a hypoxic or hyperoxic response. Depending on the organ of the body, the normoxic set point would be different due to the amount of oxygen required.[48] Hypoxia sensing and response is implicated in ischemic disease conditions, but is required for development where there is a changing state of oxygenation sending a signal to continue the wound-healing process. This sensing is either considered HIF-dependent or HIF-independent.[21]

Intermittent hypoxia, a periodic exposure to hypoxia, is interrupted by a return to normoxia where less hypoxic periods occur in many circumstances.[49] This intermittent hypoxia is mostly found in obstructive sleep apnea, but in a study by Khayat et al,[50] the authors have shown patients with this condition commonly have nonhealing wounds. Even though hyperoxia may induce some positive effects, if this occurs for a period of time exceeding the normoxic set point it can be a risk factor.[51] In areas where the wound has pockets of hypoxia, the goal is to reestablish normoxia in the areas of hypoxia without exposing the wound to high levels of oxygen which might cause oxygen toxicity.[52] Wound healing might be delayed in extreme hyperoxia which can cause growth arrest and cell death by mitochondria apoptosis.[53] The normoxic set point can be tuned when the cells are exposed to modest changes of oxygen and there is a physiological change that can possibly be an adaptive process.[54]