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Sprouting Angiogenesis: A Numerical Approach with Experimental Validation.
Annals of Biomedical Engineering ( IF 3.0 ) Pub Date : 2020-09-24 , DOI: 10.1007/s10439-020-02622-w
Ana Guerra 1 , Jorge Belinha 2 , Naside Mangir 3, 4 , Sheila MacNeil 3 , Renato Natal Jorge 5, 6
Affiliation  

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.



中文翻译:

发芽血管生成:具有实验验证的数值方法。

功能性血管网络对于正确的伤口愈合至关重要。在萌芽血管生成中,血管内皮生长因子 (VEGF) 调节从预先存在的血管形成新毛细血管。这是一个非常复杂的过程,数学公式允许使用耗时少、可重复和更便宜的方法来研究血管生成。本研究旨在模拟 VEGF 在刺激发芽血管生成中的化学引诱作用。我们开发了一个数值模型,其中内皮细胞根据 VEGF 的扩散反应方程迁移。鸡绒毛尿囊膜 (CAM) 生物测定用于获得一些重要参数以在模型中实施并验证数值结果。我们证实内皮细胞在最高 VEGF 浓度后迁移。在硅片体内的方法和相似的结果实现了(p值小于0.5; ñ = 6)。对于使用两种方法评估的总毛细管体积分数之间的差异,获得小于 15% 的值。在这项研究中,我们第一次模拟了具有真实形态和结构的 CAM 测定过程中获得的毛细血管网络。

更新日期:2020-09-25
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