Stent implantation has been widely used in the treatment of stenosed arteries to open the blocked artery and restore blood flow. Nearly 1.2 million patients undergo coronary stent implantations each year in the United States. The major complication of this intervention is instent restenosis, the reoccurrence of stenosis. Nearly one-third of stented patients require further intervention within six months due to the occurrence of restenosis. It has been speculated that stent design features contribute to the development of restenosis. In order to further understand the progression mechanism of restenosis, models capturing the correlation between stent features and restenosis statistics are needed.
The goal of this work is to develop computational models that will provide a fundamental understanding of the impact of stent implantation on vascular mechanics and the development of restenosis. The models will be reinforced through experimental validation. Computational models will be developed to capture the detailed interaction between stent design parameters, plaque properties, and artery configurations. Computational results combined with restenosis statistics will determine the impact of stents on restenosis rate. In-vitro experimental data will be utilized to provide a benchmark for validation and verification of the computational models. Restenosis involves sophisticated biological and mechanical interactions between the arterial wall, plaque, blood flow, and implanted stent. This project will explore the factors that initiate and control restenosis from the view of solid mechanics. The PI will investigate the relationship between the stent-induced arterial stain/stress and the statistics of vascular re-narrowing. Preliminary computational results indicate that stent-induced arterial strain and stress concentrations correlate with locations of cell proliferation, which led to the restenosis. This correlation requires further investigation by considering the influence of various stent designs, plaque and artery properties, and the statistics of restenosis rate.
Intellectual merit: This proposed research will provide a better understanding of the physics of stent-plaque-artery interactions with respect to changes in restenosis rate. The findings obtained in this project will elucidate the mechanism by which altered arterial stress and strain lead to vessel re-narrowing. The restenosis rate will be expressed by stent design parameters (i.e. strut thickness, strut width, pattern design, and its total length), combined with vessel and plaque properties such as symmetrical or asymmetrical plaque, degree of stenosis, and the contact area. Validated analytical models will lead to the development of novel coronary stent platforms and new treatment of restenosis. The proposed research is transformative in that it may open up an entirely new avenue for studying the initiation and progression of restenosis in the stented vessel as well as the development of arthrosclerosis.
Broader impacts: The new knowledge obtained through this project will provide a fundamental design tool for implanted stents, prompt changes in clinical practice, and improve the prevention and treatment of restenosis, which would have a tremendous positive impact on the patients that undergo stent implantations. This proposed research will develop preliminary results and collaborations that will lead to formulation of future grant applications. Both graduate and undergraduate students, especially women, will be recruited for this project from our university's pipeline programs. The PI will also provide seminars, short courses, or lab tours for young women and their teachers in an effort to continue to inform middle and high school students about the relevancy of engineering program to clinical problems. It is expected that the proposed activities will help attract and retain women to the engineering program.
This project has elucidated the mechanism of stent-plaque-artery interactions, and unraveled the positive correlation between the arterial stress and the observed clinical restenosis rate. The impact of stenting procedure on the artery were simulated for various stent designs including balloon-expandable PS stent, Express stent, Driver, and Multilink Vision stent; as well as self-expandable ev3 stent and braided wall stent (image). The stent-vessel interaction models are validated by the benchtop testing captured by the high speed camera system. We have observed that stent-induced arterial stress and strain exhibited a strong positive correlation with the reported clinical restenosis rate. This implies that arterial stress/strain could serve as one comprehensive index to predict the occurrence of restenosis. These results could be used for developing new strategies to prevent and reduce the occurrence of restenosis and improve the stent design, which would have a tremendous positive impact on millions of patients that undergo stent implantations. This project also created new opportunities to engage underrepresented groups in the engineering disciplines by demonstrating the relevancy of engineering to medical problems. Our findings were disseminated to the communities through archival publications, exhibit at the University of Nebraska State Museum, presentations for the women interested in the engineering day, as well as lab tours for young women and their teachers. In addition, this project helped to provide summer job for high school science teacher, host high school female students for their senior science project, and recruit and mentor undergraduate and graduate students.
