In Silico Prediction of the Mechanobiological Response of Arterial Tissue: Application to Angioplasty and Stenting

Abstract

One way to restore physiological blood flow to occluded arteries involves the deformation of plaque using an intravascular balloon and preventing elastic recoil using a stent. Angioplasty and stent implantation cause unphysiological loading of the arterial tissue, which may lead to tissue in-growth and reblockage; termed "restenosis." In this paper, a computational methodology for predicting the time-course of restenosis is presented. Stress-induced damage, computed using a remaining life approach, stimulates inflammation (production of matrix degrading factors and growth stimuli). This, in turn, induces a change in smooth muscle cell phenotype from contractile (as exists in the quiescent tissue) to synthetic (as exists in the growing tissue). In this paper, smooth muscle cell activity (migration, proliferation, and differentiation) is simulated in a lattice using a stochastic approach to model individual cell activity. The inflammation equations are examined under simplified loading cases. The mechanobiological parameters of the model were estimated by calibrating the model response to the results of a balloon angioplasty study in humans. The simulation method was then used to simulate restenosis in a two dimensional model of a stented artery. Cell activity predictions were similar to those observed during neointimal hyperplasia, culminating in the growth of restenosis. Similar to experiment, the amount of neointima produced increased with the degree of expansion of the stent, and this relationship was found to be highly dependant on the prescribed inflammatory response. It was found that the duration of inflammation affected the amount of restenosis produced, and that this effect was most pronounced with large stent expansions. In conclusion, the paper shows that the arterial tissue response to mechanical stimulation can be predicted using a stochastic cell modeling approach, and that the simulation captures features of restenosis development observed with real stents. The modeling approach is proposed for application in three dimensional models of cardiovascular stenting procedures.

Application of a mechanobiological simulation technique to stents used clinically

“…In comparison to our previous study (Boyle et al 2011), this study was applied to 3D arteries, and clinically relevant stent designs. This represents a first step in the direction of applying such models to medical devices as a pre-clinical design tool.…”

“…The simulation technique used in this study has been described in detail in a previous paper (Boyle et al 2011). The technique uses three interconnected models: 1.…”

“…In a previous study (Boyle et al, 2011), we developed, calibrated, and tested a cell-centred, lattice-based model, which modelled the injury, inflammation and biological response of arterial tissue to stent and angioplasty induced injury. This technique models SMC behaviour by explicitly modelling individual cells, which interact with their local environment and neighbours within a regular orthogonal lattice (Pérez & Prendergast, 2007).…”

Mathematical modeling of collagen turnover in biological tissue

“…A key contribution is the work of Fung & Liu (1989), amongst many others, which demonstrates that the volumetric growth of blood vessels induces a change in the natural configuration of the tissue, and induces residual stresses. Diffusion and cells migration models (Javierre et al, 2009;Cumming et al, 2010;Boyle et al, 2011) are other interesting approaches to the problem of biological tissue adaptation.…”

Vascular Stent Design Optimisation Using Numerical Modelling Techniques

“…More importantly, however, numerical modelling also provides a means to model the biological response to an implant using mechanobiological models whereby the mechanical environment may be used to dictate the growth and remodelling of vascular cells (Boyle et al, 2011;Zahedmanesh & Lally, 2011). With the emergence of Drug Eluting Stents (DES) and gene delivery stents, however, comes a need to include not only the growth and remodelling of the vessel wall but also the temporal and spatial distribution of such therapeutic agents and their influence on cell growth.…”