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Sprouting Angiogenesis: A Numerical Approach with Experimental Validation

Ann Biomed Eng. 2021 Feb;49(2):871-884. doi: 10.1007/s10439-020-02622-w. Epub 2020 Sep 24.

Abstract

A functional vascular network is essential to the correct wound healing. In sprouting angiogenesis, vascular endothelial growth factor (VEGF) regulates the formation of new capillaries from pre-existing vessels. This is a very complex process and mathematical formulation permits to study angiogenesis using less time-consuming, reproducible and cheaper methodologies. This study aimed to mimic the chemoattractant effect of VEGF in stimulating sprouting angiogenesis. We developed a numerical model in which endothelial cells migrate according to a diffusion-reaction equation for VEGF. A chick chorioallantoic membrane (CAM) bioassay was used to obtain some important parameters to implement in the model and also to validate the numerical results. We verified that endothelial cells migrate following the highest VEGF concentration. We compared the parameters-total branching number, total vessel length and branching angle-that were obtained in the in silico and the in vivo methodologies and similar results were achieved (p-value smaller than 0.5; n = 6). For the difference between the total capillary volume fractions assessed using both methodologies values smaller than 15% were obtained. In this study we simulated, for the first time, the capillary network obtained during the CAM assay with a realistic morphology and structure.

Keywords: Capillary network; Chick chorioallantoic membrane assay; Radial point interpolation method; Vascular endothelial growth factor.

MeSH terms

  • Animals
  • Capillaries / physiology*
  • Cell Movement
  • Chick Embryo
  • Chorioallantoic Membrane / blood supply*
  • Endothelial Cells / physiology*
  • Models, Biological*
  • Neovascularization, Physiologic*
  • Vascular Endothelial Growth Factors / physiology*

Substances

  • Vascular Endothelial Growth Factors