Biomechanical response of artery following stent implantation: Implication for restenosis

Stents have gained tremendous popularity over the past two decades, and their implantations in artery have become the most common surgical treatments for atherosclerosis-induced cardiovascular diseases (CVD). However, stent implantation could induce abnormal loading onto artery and trigger the maladaptive growth of smooth muscle cells within the artery. The abnormal growth may re-narrow the opened lumen and restrict the long-term efficacy of stents. This renarrowing phenomenon, referred to as in-stent restenosis (ISR), is one of the major complications following stent implantations and still afflicts one-third of patients regardless of the development of advanced stent designs. The fundamental mechanisms of ISR are still not well understood. To better understand the influence of stent implantation on the artery and its subsequent remodeling, the goal of this work is to develop virtual stenting procedure using computational tools, validated by the experimental observations. Clinical trials have identified various risk factors associated with the stent implantation, such as stent length, plaque properties, stent overexpansion, stent design, etc. However, the systematic studies of these parameters are lacking. In this project, the reported risk factors were systematically investigated through the stent-artery interaction models; in addition, the mechanical properties of the human artery as well as its three layers were characterized for obtaining the arterial constitutive models. Results have demonstrated that many existing risk factors could be integrated into one comprehensive risk factor: arterial stress, which is positively correlated with the reported clinical restenosis rates. The strong correlation ( r=0.97) was obtained through simulating six commercial stent trials. This correlation not only led to a new risk factor for predicting ISR, but also helped us to formulate a new hypothesis to unravel the progression of ISR. The progression of arterial remodeling in response to mechanical stimuli was developed and then compared with the reported animal studies. In addition, the integrated geometrical and material remodeling of a MRI-reconstructed artery was also implemented. This study provided a fundamental understanding of the effects of stent implantations on vascular mechanics and elucidated the mechanism by which altered stress and strain leads to ISR