Sprouting Angiogenesis: A Numerical Approach with Experimental Validation

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 angiogenesi...

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Bibliographic Details
Published in:Annals of biomedical engineering 2021-02, Vol.49 (2), p.871-884
Main Authors: Guerra, Ana, Belinha, Jorge, Mangir, Naside, MacNeil, Sheila, Natal Jorge, Renato
Format: Article
Language:English
Subjects:
Angiogenesis
Bioassays
Biochemistry
Biological and Medical Physics
Biomedical and Life Sciences
Biomedical Engineering and Bioengineering
Biomedicine
Biophysics
Blood vessels
Capillaries
Cell migration
Chorioallantoic membrane
Classical Mechanics
Endothelial cells
Growth factors
In vivo methods and tests
Mathematical models
Numerical models
Original Article
Parameters
Reaction-diffusion equations
Vascular endothelial growth factor
Wound healing
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Summary: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.
ISSN:0090-6964
1573-9686
DOI:10.1007/s10439-020-02622-w