Abstract
Vascular clamping often causes injury to arterial tissue, leading to a cascade of cellular and extracellular events. A reliable in silico 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 in vivo 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 in vivo 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.
Highlights
Multiple studies indicate that arterial occlusion by almost any type of clamp systematically leads to intimal injury at the site of application
We introduce a chemomechanical model in a constrained mixture framework, considering inflammation, collagen deposition, smooth muscle cells (SMC) proliferation, SMC active response as well as SMC switch from contractile to synthetic phenotype, all depending on the mechanical and chemical environment
From this table it can be concluded that the difference between clamping at 0.6 and 1.27 N is small in terms of acute damage
Summary
Multiple studies indicate that arterial occlusion by almost any type of clamp systematically leads to intimal injury at the site of application. Endothelial denudation is a widely known effect of clamping (Slayback et al, 1976; Barone et al, 1989; Margovsky et al, 1997, 1999; Hangler et al, 2008; Vural et al, 2008; Famaey et al, 2010; Geenens et al, 2016a,b). The tonicity of vascular smooth muscle cells (SMC) after clamping was studied extensively (Barone et al, 1989; Famaey et al, 2010; Geenens et al, 2016b). Arterial clamping was followed by an inflammatory response leading to some degree of fibrosis
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