Maes Lauranne, Vastmans Julie, Avril Stéphane, Famaey Nele
Biomechanics Section, Department of Mechanical Engineering, KU Leuven, Leuven, Belgium.
Mines Saint-Etienne, Université de Lyon, Université Jean Monnet, INSERM, Saint-Étienne, France.
Front Bioeng Biotechnol. 2021 Jan 26;8:589889. doi: 10.3389/fbioe.2020.589889. eCollection 2020.
Vascular clamping often causes injury to arterial tissue, leading to a cascade of cellular and extracellular events. A reliable prediction of these processes following vascular injury could help us to increase our understanding thereof, and eventually optimize surgical techniques or drug delivery to minimize the amount of long-term damage. However, the complexity and interdependency of these events make translation into constitutive laws and their numerical implementation particularly challenging. We introduce a finite element simulation of arterial clamping taking into account acute endothelial denudation, damage to extracellular matrix, and smooth muscle cell loss. The model captures how this causes tissue inflammation and deviation from mechanical homeostasis, both triggering vascular remodeling. A number of cellular processes are modeled, aiming at restoring this homeostasis, i.e., smooth muscle cell phenotype switching, proliferation, migration, and the production of extracellular matrix. We calibrated these damage and remodeling laws by comparing our numerical results to experimental data of clamping and healing experiments. In these same experiments, the functional integrity of the tissue was assessed through myograph tests, which were also reproduced in the present study through a novel model for vasodilator and -constrictor dependent smooth muscle contraction. The simulation results show a good agreement with the experiments. The computational model was then also used to simulate healing beyond the duration of the experiments in order to exploit the benefits of computational model predictions. These results showed a significant sensitivity to model parameters related to smooth muscle cell phenotypes, highlighting the pressing need to further elucidate the biological processes of smooth muscle cell phenotypic switching in the future.
血管夹闭常常会导致动脉组织损伤，引发一系列细胞和细胞外事件。对血管损伤后这些过程进行可靠预测，有助于我们增进对此的理解，并最终优化手术技术或药物递送，以将长期损伤降至最低。然而，这些事件的复杂性和相互依赖性使得将其转化为 constitutive laws 并进行数值实现极具挑战性。我们引入了一种考虑急性内皮剥脱、细胞外基质损伤和平滑肌细胞丢失的动脉夹闭有限元模拟。该模型捕捉了这是如何导致组织炎症以及偏离机械稳态的，二者都会引发血管重塑。对一些细胞过程进行了建模，旨在恢复这种稳态，即平滑肌细胞表型转换、增殖、迁移以及细胞外基质的产生。我们通过将数值结果与夹闭和愈合实验的实验数据进行比较，对这些损伤和重塑定律进行了校准。在这些相同的实验中，通过肌动描记法测试评估了组织的功能完整性，本研究还通过一种新的依赖血管舒张剂和收缩剂的平滑肌收缩模型对其进行了再现。模拟结果与实验结果吻合良好。然后，该计算模型还被用于模拟超过实验持续时间的愈合过程，以利用计算模型预测的优势。这些结果显示出对与平滑肌细胞表型相关的模型参数具有显著敏感性，凸显了未来进一步阐明平滑肌细胞表型转换生物学过程的迫切需求。
