Spatiotemporal remodeling of embryonic aortic arch: stress distribution, microstructure, and vascular growth in silico
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ORIGINAL PAPER
Spatiotemporal remodeling of embryonic aortic arch: stress distribution, microstructure, and vascular growth in silico S. Samaneh Lashkarinia1 · Gürsan Çoban1 · Erhan Ermek1 · Merve Çelik1 · Kerem Pekkan1 Received: 27 May 2019 / Accepted: 17 February 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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 ≈ 270 Pa (Stage 18) to a level higher than ≈ 600 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. Keywords Aortic arch · Vascular growth · Tissue remodeling · Embryonic evolution
1 Introduction Blood pressure and the vascular wall shear stress (WSS) govern the embryonic development of arterial structures as two distinct biomechanical loading modes. From a phenomenological perspective, these loading modes are associated with grossly different molecular pathways and result in distinct biological outcomes that shape the vascular morphology and augment the matrix remodeling of the embryonic great arteries. The WSS due to blood flow is sensed through the Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10237-020-01315-6) contains supplementary material, which is available to authorized users. * Kerem Pekkan [email protected] 1
Department of Mechanical Engineering, Koc University, Rumeli Feneri Kampüsü, Sariyer, Istanbul, Turkey
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