STTR Phase I: Hemodynamic Effects Inform Design of an External Stent to Reduce Dialysis Access Failures

该小企业技术转让（STTR）项目的更广泛影响/商业潜力是开发一种可改善透析患者质量和寿命的外部支架。透析是终末期肾病患者的主要生命线。不幸的是，我们目前的护理标准没有为手臂中手术创建的动脉-静脉连接提供额外的支持或治疗以启动透析（即入路部位），导致第一年内40-60%的失败率。这些失败的后果是可怕的：透析患者的严重疼痛，痛苦和死亡，医院重新入院的处罚，以及超过10亿美元的医疗保险直接成本。已经开发了在穿刺部位创建手术时包裹透析患者的静脉-动脉/移植物接合处的外部支架，以预防性方式减少这些失效。为了通过提供通过穿刺部位的有利流动条件（即血液动力学）来最大限度地提高其对透析患者生命的影响，必须首先借助计算建模在工作台上优化器械设计。这项资助的发现将进一步科学地理解外部支持和血液动力学在穿刺部位失效中的作用。该STTR第一阶段项目提出创建一个计算流体动力学（CFD）模型，该模型可以成功预测在有或没有外部支架的情况下穿刺部位的流动和变形条件，并使用该模型来识别促进最有利的血液动力学环境以防止进入部位失效的外部支架设计参数。首先，将优化3D打印制造方法，以高度可重复的方式制造外部支架，有利于大规模、符合FDA要求的生产。将根据经验结果创建CFD模型，其中在不存在或存在外部支架设计的情况下，将血管构建的血管（例如静脉-移植物连接处）暴露于动静脉模拟压力和流动条件。将通过4D flow MRI（提供整个吻合口上3D血流的空间和时间信息），在存在或不存在各种外部支架设计的情况下，从动态变形（例如扩张幅度）和流型（即速度场）的定量测量中收集用于确认CFD模型模拟结果的经验性离体数据。这项工作应导致确定一些设计，主张有利于减少新生内膜增生的血流动力学效果，入路部位failures.This奖项的罪魁祸首反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) project is to develop an external stent that can improve the quality and length of life for dialysis patients. Dialysis is the primary lifeline for End-Stage Renal Disease patients. Unfortunately, our current standard of care, which provides no additional support or treatment to the artery-vein connections surgically created in the arm to initiate dialysis (i.e. access sites), results in 40-60% failure rates within the first year. Consequences of these failures are dire: significant pain, suffering, and death for dialysis patients, hospital readmission penalties, and more than $1B in direct costs to Medicare. An external stent that wraps around the vein-artery/-graft junction of dialysis patients at the time of access site creation surgery has been developed to reduce these failures in a preventative fashion. In order to maximize the impact that it can have on the lives of dialysis patients by providing favorable flow conditions (i.e. hemodynamics) through the access site, it is imperative to first optimize device design on the bench with the aid of computational modeling. Findings from this grant will further scientific understanding of external supports and the role that hemodynamics play in access site failures.This STTR Phase I project proposes to create a computational fluid dynamic (CFD) model that successfully predicts flow and deformation conditions at the access site in the presence or absence of an external stent, and to use this model to identify external stent design parameters that promote the most favorable hemodynamic environment for preventing access site failures. First, a 3D printing method of manufacture will be optimized to enable the fabrication of external stents in a highly-repeatable manner conducive to large-scale, FDA-compliant production. A CFD model will be created from empirical results in which surgically-constructed anastomoses (e.g. vein-graft junctions) are exposed to arteriovenous-mimetic pressure and flow conditions in the absence or presence of external stent designs. Empirical ex vivo data to validate the CFD model simulation results will be collected from quantitative measurements of dynamic deformation (e.g. magnitude of expansion) and flow patterns (i.e. velocity fields) in the presence or absence of various external stent designs via 4D flow MRI, which provides spatial and temporal information on 3D flow over the entire anastomosis. This work should result in the identification of a few designs that assert hemodynamic effects conducive to reducing neointimal hyperplasia, the primary culprit of access site failures.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.