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Sprouting Angiogenesis: A Numerical Approach with Experimental Validation.

Ana Guerra1, Jorge Belinha2, Naside Mangir3,4

  • 1Institute of Science and Innovation in Mechanical and Industrial Engineering (INEGI), Rua Dr. Roberto Frias, 400, 4200-465, Porto, Portugal.

Annals of Biomedical Engineering
|September 25, 2020
PubMed
Summary
This summary is machine-generated.

This study developed a numerical model to simulate sprouting angiogenesis, mimicking vascular endothelial growth factor (VEGF) effects. The model accurately reproduced capillary network formation observed in chick assays, offering a faster, cheaper alternative for research.

Keywords:
Capillary networkChick chorioallantoic membrane assayRadial point interpolation methodVascular endothelial growth factor

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Area of Science:

  • Biomedical Engineering
  • Computational Biology
  • Vascular Biology

Background:

  • A functional vascular network is crucial for effective wound healing.
  • Sprouting angiogenesis, regulated by vascular endothelial growth factor (VEGF), involves new capillary formation from existing vessels.
  • Mathematical modeling offers a reproducible, cost-effective, and time-efficient approach to studying complex biological processes like angiogenesis.

Purpose of the Study:

  • To develop and validate a numerical model that mimics the chemoattractant effect of VEGF in stimulating sprouting angiogenesis.
  • To compare in silico modeling results with in vivo data from a chick chorioallantoic membrane (CAM) assay.
  • To simulate the realistic morphology and structure of capillary networks formed during angiogenesis.

Main Methods:

  • Development of a numerical model based on a diffusion-reaction equation for VEGF to simulate endothelial cell migration.
  • Utilization of a chick chorioallantoic membrane (CAM) bioassay to acquire parameters for the model and validate numerical outcomes.
  • Comparison of key angiogenic parameters (total branching number, total vessel length, branching angle, and capillary volume fraction) between in silico and in vivo methodologies.

Main Results:

  • Endothelial cells were observed to migrate towards the highest concentrations of VEGF in the model.
  • Similar results were achieved when comparing in silico and in vivo data for total branching number, total vessel length, and branching angle (p < 0.5, n = 6).
  • The difference in total capillary volume fractions between the two methodologies was less than 15%.

Conclusions:

  • The numerical model successfully simulated capillary network formation with realistic morphology and structure, comparable to experimental CAM assay results.
  • This study presents the first simulation of a capillary network obtained during a CAM assay with realistic morphology and structure.
  • The findings suggest that computational modeling is a viable and efficient tool for studying sprouting angiogenesis and can aid in understanding wound healing processes.