Vertically Integrated Approach to Design a Biologically and Mechanically Optimized Vascular Conduit for Dialysis Vascular Access

ABSTRACT Dialysis vascular access (arteriovenous fistulae [AVF] and arteriovenous grafts [AVG]) is the Lifeline for the 500,000+ patients on hemodialysis in the United States (3million+ worldwide). Unfortunately, both AVFs and AVGs have high failure rates due to an aggressive venous segment stenosis which results in multiple interventional procedures, hospitalizations, and increased catheter (CVC) use. This results in vascular access also being the Achilles Heel of hemodialysis and an important unmet clinical need which results in a very significant morbidity, mortality, and economic cost (over 5B USD per annum). In this proposal we will combine expertise and experience from both industry and academia to create an innovative vascular conduit (the Functional INtegrated Electrospun [FINE] device) that comprises an inner Cu-PAS core surrounded by an outer P4HB sheath that will have (a) a precisely controlled microstructure to promote host cell integration (b) anti-bacterial and immunomodulatory properties (c) vein-artery-matched geometry to minimize upstream injury pathways and (d) an intrinsic self-sealing ability that allows for early cannulation. At an operational level we plan to (a) selectively design, refine and prototype FINE devices (b) document the safety and efficacy of selected FINE devices in a pig arteriovenous access stenosis model and (c) develop clinical scale production capabilities for the FINE device. In summary, this proposal brings together a trio of unlikely partners (industry x 1 and academia x 2) that between them have the science, the infrastructure, the experience, and the people to bring disruptive change to dialysis vascular access. While none of us on our own could have done what is described in this proposal, we would also venture to say that the sum of the individual parts will in this case be exponentially larger than the whole.