3D modelling of in-stent restenosis

In this thesis a fully-coupled 3D multiscale computational model of in-stent restenosis is developed, which describes the process of post-stenting tissue growth, and is validated against in vivo and in vitro data.
First, a fully-coupled 3D model of in-stent restenosis (ISR) is described, which includes models for smooth muscle cell (SMC) mechanics and biology in the vessel wall, as well as for the blood flow through the vessel. The model is calibrated using experimental data, and the obtained results are compared to the results obtained by an earlier 2D model built on similar principles, as well as to the in vivo data.
Uncertainty quantification (UQ) and sensitivity analysis (SA) are performed for a simplified 2D version of the ISR model. It is shown how the variation of endothelial regeneration, as well as the flow velocity in the channel, affects the restenosis development, according to the model. It also shows whether knowing the exact value of a parameter is important for the precision of the simulation results.
Additionally, an in silico endothelial cell migration model based on in vitro data under flow conditions is developed. The results from the simulation are compared to the dynamics reported for two different experimental in vitro setups.
The effects of varying flow and of different coronary anatomy on the restenosis progression are considered, using the 2D version of the model.
Based on these results, a modification of the initial multiscale 3D model is developed and validation is performed against detailed porcine data.