HELical Biodegradable Photochemical(HELP)Stents for AVF Maturation

Inovasc, Llc, Cincinnati OH

Investigators

Abstract

ABSTRACT Although arteriovenous fistulae (AVFs) are the preferred mode of dialysis vascular access, over 50% fail to ?mature?, in that they do not develop an adequate blood flow or diameter to support hemodialysis. This results in a very significant clinical morbidity and economic cost. At a pathogenetic level, AVF maturation failure is due to (a) small vessels (b) ?bad? non-laminar hemodynamic profiles that likely result in a more aggressive stenosis, due to endothelial cell dysfunction and (c) abnormal baseline vascular biology due to uremia and oxidative stress. The central hypothesis for this proposal is that the placement of a HELical biodegradable Photochemically etched (HELP) stent at the time of AVF creation will (a) dilate small veins (b) create ?good? hemodynamics through the generation of spiral laminar flow (c) have the future potential to optimize ?local uremic vascular biology? through selected coatings (drugs, cells or chemicals), and so ?help? with AVF maturation. We plan to address this central hypothesis through a series of specific aims that focus on (a) fabrication of HELP stents that have an optimized flow profile in-vitro (Specific Aim 1 = Engineering Aim) (b) demonstration of in-vivo degradation and toxicity profiles (Specific Aim 2 = Biocompatibility and Toxicity Aim) (c) in-vivo proof of principle experiments to document therapeutic efficacy (flow and diameter; Specific Aim 3 = Therapeutic Aim). In summary, there is clearly a huge and unmet clinical need for novel therapies to enhance AVF maturation (there are currently no effective therapies for this). In addition, the innovative photochemical technology described in this proposal lends itself to mass production and subsequent economies of scale. As a result we strongly believe that the HELP stent is an important platform technology that could deliver improved patient outcomes at reduced cost, thus adding overall value to the care of hemodialysis patients.