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

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.