Biodegradable Magensium Stents to Enhance AV Fistula Maturation

描述（由申请人提供）：尽管动静脉瘘（avf）是透析血管通路的首选模式，但超过50%的动静脉瘘未能“成熟”，因为它们没有足够的血流或直径来支持血液透析。这导致了非常显著的临床发病率和经济成本。在病理水平上，AVF成熟失败是由于(a)血管小(b)“不良”血流动力学，不允许释放血管扩张剂分子，如一氧化氮和(c)由于尿毒症和氧化应激导致的血管生物学异常。该建议的中心假设是，在房室瘘形成时放置可塑的、包被的（药物/细胞/基因/化学）、可生物降解的成熟增强支架（bMES）将(a)扩张小静脉(b)优化解剖结构以改善血流动力学(c)由于包被剂的作用而改善“局部”血管生物学。我们计划通过一系列具体目标来解决这一中心假设，这些目标侧重于(a) bMES的体内降解概况和毒性(b)体内原理实验证明，以记录有关流量和直径的功效。我们认为，对于可能促进房室瘘成熟的新疗法存在巨大的未满足的临床需求，如果成功，bMES的概念可以显著降低与房室瘘成熟失败相关的巨大临床发病率和经济成本。

DESCRIPTION (provided by applicant): 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" hemodynamics that do not allow for the release of vasodilator molecules such as nitric oxide and (c) abnormal vascular biology due to uremia and oxidative stress. The central hypothesis for this proposal is that the placement of a malleable, coated (drug/cell/gene/chemical), biodegradable maturation enhancing stent (bMES) at the time of AV fistula creation will (a) dilate small veins (b) optimize anatomical configuration in order to improve hemodynamics and (c) improve upon "local" vascular biology as a result of the coated agents. We plan to address this central hypothesis through a series of specific aims that focus on (a) in-vivo degradation profile and toxicity for the bMES (b) in-vivo proof of principle experiments to document efficacy with regard to flow and diameter. We believe that there is a huge unmet clinical need for novel therapies that might enhance AV fistula maturation and that if successful, the concept of bMES could significantly reduce the huge clinical morbidity and economic cost associated with AVF maturation failure.