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Spatiotemporal remodeling of embryonic aortic arch: stress distribution, microstructure, and vascular growth in silico.
Biomechanics and Modeling in Mechanobiology ( IF 3.5 ) Pub Date : 2020-03-04 , DOI: 10.1007/s10237-020-01315-6
S Samaneh Lashkarinia 1 , Gürsan Çoban 1 , Erhan Ermek 1 , Merve Çelik 1 , Kerem Pekkan 1
Affiliation  

The microstructure for mature vessels has been investigated in detail, while there is limited information about the embryonic stages, in spite of their importance in the prognosis of congenital heart defects. It is hypothesized that the embryonic vasculature represents a disorganized but dynamic soft tissue, which rapidly evolves toward a specialized multi-cellular vascular structure under mechanical loading. Here the microstructural evolution process of the embryonic pharyngeal aortic arch structure was simulated using an in ovo validated long-term growth and remodeling computational model, implemented as an in-house FEBio plug-in. Optical coherence tomography-guided servo-null pressure measurements are assigned as boundary conditions through the critical embryonic stages. The accumulation of key microstructural constituents was recorded through zoom confocal microscopy for all six embryonic arch arteries simultaneously. The total amount and the radial variation slope of the collagen along the arch wall thickness in different arch types and for different embryonic times, with different dimension scales, were normalized and compared statistically. The arch growth model shows that the stress levels around the lumen boundary increase from \(\approx 270 \;{\text{Pa}}\) (Stage 18) to a level higher than \(\approx 600 \;{\text{Pa}}\) (Stage 24), depending on matrix constituent production rates, while the homeostatic strain level is kept constant. The statistical tests show that although the total collagen levels differentiate among bilateral positions of the same arch, the shape coefficient of the matrix microstructural gradient changes with embryonic time, proving radial localization, in accordance with numerical model results. In vivo cell number (DAPI) and vascular endothelial growth factor distributions followed similar trends.



中文翻译:

胚胎主动脉弓的时空重塑:应力分布,微结构和硅管的血管生长。

成熟血管的微观结构已进行了详细研究,而有关胚胎的信息有限尽管它们在先天性心脏缺损的预后中具有重要意义。假设胚胎脉管系统代表了杂乱无章但动态的软组织,其在机械负荷下迅速演变成专门的多细胞血管结构。在这里,使用内部验证的长期生长和重塑计算模型(通过内部FEBio插件实现)模拟了胚胎咽主动脉弓结构的微结构演变过程。光学相干层析成像引导的伺服零压力测量值被指定为贯穿关键胚胎阶段的边界条件。通过变焦共聚焦显微镜同时记录了所有六个胚胎弓形动脉的关键微结构成分的积累。对不同弓形类型,不同胚胎时期,不同尺寸尺度的胶原蛋白沿着弓形壁厚度的总量和径向变化斜率进行标准化并进行统计学比较。足弓生长模型表明,管腔边界周围的应力水平从\(\ approx 270 \; {\ text {Pa}} \)(阶段18)高于\(\ approx 600 \; {\ text {Pa}} \\)(阶段24),具体取决于矩阵组成生产速度,而稳态应变水平保持恒定。统计测试表明,尽管总胶原水平在同一个弓的双侧位置之间有所区别,但根据数值模型结果,基质微结构梯度的形状系数随胚胎时间而变化,证明径向定位。体内细胞数量(DAPI)和血管内皮生长因子分布遵循相似的趋势。

更新日期:2020-03-04
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