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Sprouting Angiogenesis: A Numerical Approach with Experimental Validation

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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.

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Acknowledgements

The authors truly acknowledge the funding provided by Ministério da Ciência, Tecnologia e Ensino Superior - Fundação para a Ciência e a Tecnologia (Portugal), under Grant SFRH/BD/133894/2017. Additionally, the authors acknowledge the funding provided by LAETA, under project UIDB/50022/2020.

Conflict of interest

Author Ana Guerra, from Institute of Science and Innovation in Mechanical and Industrial Engineering, declare that she has no conflict of interest. Author Jorge Belinha, from School of Engineering, Polytechnic of Porto, declare that he has no conflict of interest. Author Naside Mangir, from Kroto Research Institute and Royal Hallamshire Hospital, declare that she has no conflict of interest. Author Sheila MacNeil, from Kroto Research Institute, declare that she has no conflict of interest. Author Renato Natal Jorge, from Faculty of Engineering of the University of Porto, declare that he has no conflict of interest.

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Authors and Affiliations

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

    Ana Guerra

  2. Mechanical Engineering Department, School of Engineering, Polytechnic of Porto (ISEP), Rua Dr. António Bernardino de Almeida, 431, 4249-015, Porto, Portugal

    Jorge Belinha

  3. Kroto Research Institute, Department of Material Science and Engineering, University of Sheffield, North Campus, Broad Lane, Sheffield, S3 7HQ, UK

    Naside Mangir & Sheila MacNeil

  4. Department of Urology, Royal Hallamshire Hospital, Glossop Rd, Sheffield, S10 2JF, UK

    Naside Mangir

  5. Associated Laboratory for Energy, Transports and Aeronautics (LAETA – INEGI), Rua Dr. Roberto Frias, 400, 4200-465, Porto, Portugal

    Renato Natal Jorge

  6. Mechanical Engineering Department, Faculty of Engineering of the University of Porto (FEUP), Rua Dr. Roberto Frias, 4200-465, Porto, Portugal

    Renato Natal Jorge

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  1. Ana Guerra
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  2. Jorge Belinha
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  3. Naside Mangir
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  4. Sheila MacNeil
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  5. Renato Natal Jorge
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Correspondence to Renato Natal Jorge.

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Associate Editor Estefanía Peña oversaw the review of this article.

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Guerra, A., Belinha, J., Mangir, N. et al. Sprouting Angiogenesis: A Numerical Approach with Experimental Validation. Ann Biomed Eng 49, 871–884 (2021). https://doi.org/10.1007/s10439-020-02622-w

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