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

这个小型企业技术转移(STTR)项目的更广泛的影响/商业潜力是开发一种外部支架，可以改善透析患者的质量和寿命。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，没有为手术在手臂上建立的动静脉连接提供额外的支持或治疗，以启动透析(即进入部位)，导致在第一年内有40%-60%的失败率。这些失败的后果是可怕的：透析患者的巨大痛苦、痛苦和死亡，重新入院的罚款，以及超过10亿美元的医疗保险直接成本。一种外部支架已经被开发出来，它在创建进入部位手术时包裹在透析患者的静脉-动脉/移植物交界处，以预防的方式减少这些失败。为了最大限度地提高血液透析患者的生命质量，通过入口部位提供良好的血流条件(即血流动力学)，首先必须借助计算模型来优化工作台上的设备设计。这项拨款的发现将进一步科学地了解外部支架和血流动力学在入路部位故障中所起的作用。这项STTR第一阶段项目建议创建一个计算流体动力学(CFD)模型，该模型能够成功地预测在有或没有外部支架的情况下入路部位的流动和变形状况，并使用该模型来确定外部支架设计参数，以促进最有利的血流动力学环境以防止入路部位故障。首先，3D打印制造方法将得到优化，使外部支架的制造能够以高度可重复的方式进行，有利于大规模、符合FDA的生产。CFD模型将从实验结果中创建，在没有或存在外部支架设计的情况下，手术构建的吻合口(例如静脉-移植物连接处)暴露在动静脉模拟压力和流动条件下。验证CFD模型模拟结果的经验体外数据将通过4D Flow MRI从动态变形(例如扩张幅度)和流动模式(即速度场)的定量测量中收集，这些测量是在存在或不存在各种外部支架设计的情况下进行的，它提供了整个吻合口上3D流动的空间和时间信息。这项工作的结果应该是确定几个有助于减少新生内膜增生的血流动力学效应的设计，新生内膜增生是接入部位故障的主要罪魁祸首。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.