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

STTR 第一阶段：血流动力学效应为外部支架的设计提供信息，以减少透析通路失败

• 批准号: 1819996
• 负责人: Timothy Boire
• 金额: $ 22.45万
• 依托单位: VenoStent, Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1819996&HistoricalAwards=false
• 关键词: STTR; Phase; Hemodynamic; Effects; Inform

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.

这项小型企业技术转移（STTR）项目的更广泛影响/商业潜力是开发一种可以改善透析患者质量和延长生命的外部支架。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，没有提供额外的支持或治疗手术在手臂上创建的动脉静脉连接，以启动透析（即通路），导致40-60%的失败率在第一年。这些失败的后果是可怕的：严重的疼痛、痛苦和透析患者的死亡，再入院的处罚，以及超过10亿美元的医疗保险直接成本。已经开发出一种外部支架，在透析患者的静脉-动脉/移植物连接处包裹，以预防方式减少这些失败。为了通过通道提供良好的流动条件（即血流动力学），使其对透析患者生命的影响最大化，首先必须借助计算建模优化台架上的设备设计。这项资助的研究结果将进一步科学地理解外部支持和血流动力学在通路失败中所起的作用。本STTR一期项目拟建立计算流体动力学（CFD）模型，成功预测在有或没有外部支架的情况下通路部位的流动和变形情况，并利用该模型确定外部支架设计参数，以促进最有利的血流动力学环境，防止通路部位失效。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标准的生产。将根据经验结果创建CFD模型，在没有或存在外部支架设计的情况下，将手术构建的吻合口（例如静脉-移植物结）暴露于模拟动静脉的压力和流动条件下。为了验证CFD模型的仿真结果，将通过4D流动MRI对存在或不存在各种外部支架设计时的动态变形（如膨胀幅度）和流动模式（即速度场）进行定量测量，从而收集经验的体外数据，该数据提供了整个吻合口的三维流动的时空信息。这项工作应该导致确定一些设计，断言血流动力学效果有利于减少内膜增生，这是通道部位失败的罪魁祸首。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。