Ischaemic heart disease, causing restriction of arterial blood flow to the heart tissue, can be treated with mechanical revascularisation treatments such as balloon angioplasty and stent implantation. One remaining limitation to the success of these treatments is the re-blockage of the treated artery, termed restenosis. The paradigm of re-blockage as the tissue’s response to injury has been proposed to explain restenosis in stents and corroborated with pathological studies. This paradigm has never been used to form the basis of a predictive theoretical model of restenosis. In this thesis, the hypothesis that mechanically-induced injury stimulates restenosis is tested by developing a simulation technique based on this paradigm. The model explicitly simulates the response of individual cells to injuryinduced inflammation.

A model based on a vessel-wall stress threshold for injury and smooth muscle cell phenotype modulation was developed and tested by applying it to two stents known to induce differing amounts of restenosis in vivo. The model predicted similar differences between stents, but only when a lowlevel inflammation response was prescribed, demonstrating the importance of inflammation on restenosis prediction.

The algorithms for injury prediction, inflammation and smooth muscle cell phenotype were then refined in a two dimensional model. The new simulation procedure was capable of being calibrated to human balloon angioplasty data, and predicted a correlation between stent expansion and restenosis. Inflammation intensity was found to increase this correlation.

The refined model was then re-implemented in three dimensions, and tested on three clinically-available coronary stents of differing design. The model predicted a relative difference between stents similar to that found in clinical trials.

These results corroborate the paradigm that neointimal hyperplasia is injury-induced. The technique can differentiate between stent designs based on a prediction of long-term lumen geometry, rather than solely on a mechanical analysis. The technique could be applied to novel revascularisation treatments and device designs.