The most critical determinant of restoration of tissue structure during wound healing is the re-establishment of a functional vasculature, which largely occurs via angiogenesis (i.e. capillary sprouting from pre-existing vasculature). Adult 8-10 week old male Balb/c mice weighing between 22-27g were used for the study. Animals were anaesthetised with a neuroleptoanalgesic mix of Hypnorm/Hypnovel and window chamber surgery was undertaken as previously described (Guerreiro-Lucas et al. 2008). Experimentally we used confocal microscopy to capture sequential images of perfused vascular segments within the injured panniculus carnosus muscle in the mouse dorsal skin-fold window chamber to quantify a range of morphological parameters during the first 9 days of healing. This data was then used to inform a mathematical model of sequential growth of the vascular plexus. The modelling framework mirrors the circular wound domain of the experiment and incorporates capillary sprouting and endothelial cell sensing of VEGF gradients. Vessel densities, branch point distributions, and wound areas obtained from the corresponding virtual wound are found to be in excellent agreement both temporally and spatially with data measured during the in vivo healing process. Moreover, perturbing the proliferative ability of endothelial cells in the mathematical model is found to cause a severe reduction in vascular growth and a poor healing prognosis. These predictions are subsequently shown to correlate extremely well with experimental data obtained from animals treated with an agent that targets endothelial proliferation (TNP-470). The combined approach of in vivo longitudinal analysis (i.e. over time) and mathematical modelling employed in this study establishes an experimental paradigm with which to validate experimental hypotheses associated with a wide range of wound-related disorders.
University of Manchester (2010) Proc Physiol Soc 19, SA28
Research Symposium: Dynamics of angiogenesis during wound healing: a coupled in vivo and in silico paradigm
M. Chaplain1, S. McDougall2, C. Mitchell3, A. Devlin3, M. Watson2, M. Machado3
1. Division of Mathematics, University of Dundee, Dundee, United Kingdom. 2. Petroleum Engineering, Heriot-Watt University, Edinburgh, United Kingdom. 3. Centre for Molecular Biosciences, University of Ulster, Coleraine, Coleraine, United Kingdom.
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