Influence of oxygen on wound healing dynamics: assessment in a novel wound mouse model under a variable oxygen environment.

Although oxygen is essential for the wound healing process, tissue hypoxia is known to stimulate angiogenesis. To explore these inconsistent findings, we estimated the influence of the oxygen environment on wound healing with our original model. Experiment 1 (Establishment of the model): To modify the topical oxygen tension, oxygen impermeable (polyvinylidene chloride) and permeable (polymethylpentene) membranes were applied to symmetrical excisional wounds in ddy mice (n = 6). Oxygen tension under the membrane was quantified with a device using photo-quenching technique. Experiment 2 (Influence of oxygen environment on wound healing): The wound area, granulation thickness and vascular density were analyzed under different oxygen environments (n = 24). Experiment 1: The permeable group maintained equivalent oxygen level to atmosphere (114.1±29.8 mmHg on day 7), while the impermeable group showed extremely low oxygen tension (5.72±2.99 mmHg on day 7). Accordingly, each group was defined as the normoxia group and the hypoxia group. Experiment 2: Percent decrease in wound size was significantly enhanced in the normoxia group (11.1±1.66% on day 7) in comparison with the hypoxia group (27.6±3.47% on day 7). The normoxia group showed significantly thicker granulation tissue than the hypoxia group (491.8±243.2 vs. 295.3±180.9 µm). Contrarily, the vascular density of the hypoxia group significantly increased on day 7 (0.046±0.025 vs. 0.011±0.008 mm(2)/mm(2)). Our original model successfully controlled local oxygen concentration around the wound, and the hypoxic wounds showed increased angiogenesis but with a smaller amount of granulation tissue and delayed wound closure. Enhanced neovascularization in the hypoxic group likely implies compensative response to an insufficient ambient oxygen supply.