Multiscale bio-chemo-mechanical model of intimal hyperplasia

Abstract

We consider a computational multiscale framework of a bio-chemo-mechanical model for intimal hyperplasia. With respect to existing models, we investigate the interactions between hemodynamics, cellular dynamics and biochemistry on the development of the pathology. Within the arterial wall, we propose a mathematical model consisting of kinetic differential equations for key vascular cell types, collagen and growth factors. The luminal hemodynamics is modelled with the Navier-Stokes equations. Coupling hypothesis among time and space scales are proposed to build a tractable modelling of such a complex multifactorial and multiscale pathology. A one-dimensional numerical test-case is presented for validation by comparing the results of the framework with experiments at short and long timescales. Our model permits to capture many cellular phenomena which have a central role in the physiopathology of intimal hyperplasia. Results are quantitatively and qualitatively consistent with experimental findings at both short and long timescales.

An intricate interplay between stent drug dose and release rate dictates arterial restenosis

“…In agreement with [33,34,45,48,50], greater neointimal thickness was observed in regions where WSS was low. Furthermore, Jansen et al [51] devised a multiscale bio-chemo-mechanical model of intimal hyperplasia, where haemodynamic indices are coupled to restenosis in an idealised artery through an influx of growth factors. Although CFD is included within these models [34,45,49], the role of stent deployment on arterial healing is not considered, as is present in [19][20][21]25,38]; a feature ubiquitously linked to neointimal thickening [52,53].…”

“…[25,38]), we assume that damage induced by stent deployment is the predominant driver of the biological cascade of events that initiate the healing process. Alternative approaches in the literature include linking haemodynamic indices such as WSS to a damage index [49], a function describing endothelial dysfunction [45] or an influx of growth factors [51]. Damage, d (r, z, t), is modelled as a spatiotemporal variable mapped throughout the domain in response to the stresses present following stent expansion.…”