Leveraging “Smart Stent” Platform Technologies for AVF Maturation and More

ABSTRACT Dialysis vascular access is the Lifeline for the 500,000 plus patients currently on hemodialysis in the United States (3 million+ worldwide). Unfortunately, due to the complications associated with dialysis vascular access, it is also the Achilles Heel of hemodialysis. We and others have previously demonstrated that good early AVF blood flow (1 day - 6 weeks) is the most powerful predictor of AVF success and failure. In an attempt to optimize early blood flow profiles, we have previously developed a biodegradable magnesium stent that increases early AVF flow and diameter (at 1-2 weeks), but which also unfortunately causes later neointimal hyperplasia (NH) and stenosis because of a slow (and fixed) degradation rate (needed to prevent early collapse of the stent). The central goal of this proposal, therefore, is that the application of the Smart ArterioVEnous (SAVE) stent technology through a magnetically operated galvanic corrosion electro-chemistry loop will allow for the SAVE stent to switch from a non-degrading to degrading mode at a fixed early time point (likely 2 weeks), thus maximizing the early scaffolding and balloon dilation effect, but minimizing the later stenotic effect (due to neointimal hyperplasia). We aim to achieve this central goal through the following Specific Aims. In Specific Aim 1 we will detail the scaffold strength and degradation profiles of the smart stent on the bench. In Specific Aim 2 we will describe in-vivo technical feasibility, toxicity and degradation in a validated pig model of AVF stenosis. And finally, in Specific Aim 3 we will document the clinical efficacy of the SAVE stent compared to a standard Mg stent and a control AVF. In summary, the current proposal is both significant and innovative because it would allow us to get away from the current one size fits all paradigm for vascular access care to a future individualized and precision medicine approach where the SAVE stent could be switched to degradation mode only when the AVF flow is predictive of AVF success. We strongly believe that this series of high risk, high reward experiments targeting the intractable clinical problem of AVF maturation failure, could significantly reduce the morbidity, mortality and economic cost associated with vascular access failure, and most importantly, greatly improve the quality of life of our patients. Last but not least this is clearly a platform technology which could also be applied to other vascular beds (coronaries, carotids and peripheral arteries) and to non-vascular settings such as tracheal, hepatobiliary and ureteral stenoses as also to orthopedic applications (plates and screws).