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

该SBIR II期项目旨在开发一种外部支架，以提高透析患者的生活质量和寿命。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40-70%的失败率。这些失败通常是由于静脉对高压、高流量动脉环境的适应不良，其中静脉壁内的细胞向内迁移和生长，导致流动阻塞。其后果是可怕的：透析患者的严重疼痛、痛苦和死亡，再入院的处罚，以及医疗保险的数十亿美元直接成本。血液透析开始后的一年死亡率为22%，这在很大程度上是由于穿刺部位的静脉故障，需要依赖中心导管，这大大增加了感染、血栓形成和死亡的风险-将生存率降低到仅仅是抛硬币。尽管一些有前途的临床前研究涉及外部支架，有没有在美国市场上，以防止进入网站的失败，部分原因是由于不适当的生物材料的选择和设备design.To解决这些问题，外部支架，或围绕静脉动脉连接包裹，在这个项目中开发。该包裹物为静脉提供了关键的定制机械支撑和向外生长，以帮助其以这种生物材料特有的方式更好地适应高压、高流量动脉环境。为了实现该技术改善静脉通畅性的潜力，进而改善透析患者的生命，需要进行计算流体动力学（CFD）建模实验以优化器械设计。计算模型将在生理压力下通过4D Flow MRI实验进行经验验证，其中随着时间的推移跟踪的三维速度曲线使实际实验与计算模型交叉匹配。该建模是用来自利用人动脉和静脉的离体实验和绵羊体内实验的动脉-静脉连接完成的。通过与质量合同制造商合作，实现符合FDA要求的器械质量制造，并评估生物相容性。最后，在符合FDA要求的大型动物模型中测试优化设计。该项目的最终成果将是更好地理解血液动力学的原因和预防静脉衰竭，并开发一种外部支架，可以最终影响-甚至挽救-透析患者的生命。该奖项反映了NSF的法定使命，并已被认为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。

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.