SBIR Phase II: Hemodynamic Optimization and Preclinical Assessment of a Shape Memory Polymer Wrap to Reduce Hemodialysis Access Site Failures

SBIR二期项目旨在开发一种体外支架，以提高透析患者的质量和寿命。透析是肾功能衰竭（即终末期肾病（ESRD））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40-70%的失败率在第一年。这些失败通常是由于静脉不适应高压、高流量的动脉环境，在这种环境中，静脉壁内的细胞向内迁移和生长，导致血流阻塞。其后果是可怕的：严重的疼痛，痛苦和透析患者的死亡，医院再入院罚款，以及数十亿美元的医疗保险直接成本。血液透析开始后的一年死亡率为22%，很大程度上是由于静脉衰竭，需要依赖集中导管，这大大增加了感染、血栓形成和死亡的风险，使患者的存活率降低到仅仅是抛硬币。尽管一些涉及外支架的临床前研究很有前景，但美国市场上没有任何东西可以防止进入部位失败，部分原因是不适当的生物材料选择和设备设计。为了解决这些问题，该项目开发了一种外部支架，或包裹在静脉-动脉连接处。包裹提供了关键的、定制的机械支撑和向外生长的静脉，以这种生物材料独特的方式帮助它更好地适应高压、高流量的动脉环境。为了实现该技术改善静脉通畅的潜力，从而改善透析患者的生命，需要进行计算流体动力学（CFD）建模实验来优化设备设计。计算模型将在生理压力和流动下通过4D Flow MRI实验进行经验验证，其中随时间跟踪的三维速度剖面可以将实际实验与计算模型交叉匹配。这种建模是通过动静脉连接完成的，这些动静脉连接来自于利用人类动脉和静脉的离体实验，以及羊的体内实验。通过与质量合同制造商合作，实现了器械的质量，符合fda标准的制造，并评估了生物相容性。最后，在符合fda标准的大型动物模型上对优化设计进行了测试。该项目的最终成果将是更好地了解静脉衰竭的血流动力学原因和预防，以及开发最终影响甚至挽救透析患者生命的外部支架。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。

This SBIR Phase II project aims to develop an external stent to improve the quality and length of life for dialysis patients. Dialysis is the primary lifeline for patients with failed kidneys (i.e. End-Stage Renal Disease (ESRD)). 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 40-70% failure rates within the first year. These failures are most often due to the vein's maladaptation to the high pressure, high flow arterial environment in which cells within the vein wall migrate and grow inwards, causing obstruction of flow. Consequences of this are dire: significant pain, suffering, and death for dialysis patients, hospital readmission penalties, and billions of dollars in direct costs to Medicare. The one-year mortality rate upon hemodialysis initiation is 22%, in large part due to vein failures at the access site that necessitate reliance on a centralized catheter that drastically increases risk of infection, thrombosis, and death - reducing survival to merely a coin flip. Despite some promising preclinical studies involving external stents, there is nothing on the US market to prevent access site failures, in part due to inappropriate biomaterial selection and device design.To address these issues, an external stent, or wrap around the vein-artery connection, is developed in this project. The wrap provides critical, custom-fit mechanical support and outward growth to the vein to help it adapt better to the high pressure, high flow arterial environment in a manner unique to this biomaterial. To realize the potential of this technology to improve vein patency and, in turn, the lives of dialysis patients, computational fluid dynamic (CFD) modeling experiments need to be conducted to optimize device design. The computational models will be validated empirically under physiological pressures and flows through 4D Flow MRI experiments in which three-dimensional velocity profiles tracked over time enable cross-matching of actual experiments to computational models. This modeling is done with artery-vein connections from both ex vivo experiments utilizing human arteries and veins, and in vivo in sheep. Quality, FDA-compliant manufacturing of devices is enabled through collaboration with quality contract manufacturers, and biocompatibility is assessed. Lastly, the optimized design is tested in an FDA-compliant large animal model. The final outcomes of this project will be a better understanding of hemodynamics causal and preventative of vein failures, and development of an external stent that can that can ultimately impact - or even save - dialysis patients' lives.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.