BRIGE: Stent-Induced Arterial Strain and Stress as a Determinant of Restenosis

0926880血管内支架植入术已被广泛应用于动脉狭窄的治疗，以打开阻塞的动脉，恢复血液流动。在美国，每年有近120万患者接受冠状动脉支架植入。这种干预的主要并发症是立即再狭窄，狭窄的再次发生。由于再狭窄的发生，近三分之一的支架患者在6个月内需要进一步干预。据推测，支架设计的特点有助于再狭窄的发展。为了进一步了解再狭窄的进展机制，需要建立能够捕捉支架特征与再狭窄统计数据之间相关性的模型。这项工作的目标是开发计算模型，以提供对支架植入对血管力学和再狭窄发展的影响的基本理解。模型将通过实验验证得到强化。将开发计算模型来捕获支架设计参数、斑块特性和动脉构型之间的详细相互作用。计算结果结合再狭窄统计将确定支架对再狭窄率的影响。体外实验数据将用于为计算模型的验证和验证提供基准。再狭窄涉及动脉壁、斑块、血流和植入支架之间复杂的生物和机械相互作用。本项目将从固体力学角度探讨引发和控制再狭窄的因素。PI将研究支架引起的动脉染色/应力与血管再狭窄统计之间的关系。初步计算结果表明，支架诱导的动脉应变和应力浓度与细胞增殖的位置相关，从而导致再狭窄。这种相关性需要进一步研究，考虑各种支架设计、斑块和动脉特性的影响，以及再狭窄率的统计数据。智力优势：本研究将更好地理解支架-斑块-动脉相互作用与再狭窄率变化之间的物理关系。本项目的研究结果将阐明动脉应力和应变改变导致血管再狭窄的机制。再狭窄率将由支架设计参数（即支架厚度、支架宽度、支架图案设计及其总长度）结合血管和斑块特性（如对称或不对称斑块、狭窄程度、接触面积）来表示。验证的分析模型将导致新型冠状动脉支架平台的发展和再狭窄的新治疗方法。提出的研究是变革性的，因为它可能为研究支架血管再狭窄的开始和进展以及关节硬化的发展开辟了一条全新的途径。更广泛的影响：本项目获得的新知识将为植入支架的设计提供基础性的工具，促进临床实践的变革，提高再狭窄的预防和治疗水平，对接受支架植入的患者将产生巨大的积极影响。这项拟议的研究将产生初步结果和合作，从而制定未来的资助申请。研究生和本科生，特别是女性，将从我们大学的管道项目中招募。PI还将为年轻女性和她们的老师提供研讨会、短期课程或实验室参观，以继续向初高中学生介绍工程项目与临床问题的相关性。预计拟议的活动将有助于吸引和留住女性到工程项目。

0926880GuStent 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 developmentof 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 beutilized 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.