Biodegradable Magensium Stents to Enhance AV Fistula Maturation

可生物降解的镁支架促进动静脉瘘成熟

• 批准号: 8554769
• 负责人: PRABIR ROY-CHAUDHURY
• 金额: $ 18.52万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8554769
• 关键词: Address; Angioplasty; Animal Model; Animals; Arteriovenous fistula; Biology; Blood Vessels; Blood flow; Caliber; Cells; Chemicals; Clinical; Data; Dialysis procedure; Drug Delivery Systems; Failure; Family suidae; Figs - dietary; Fistula; Genes; Grant; Hemodialysis; Hyperplasia; Infection; Inflammation; Laboratories; Magnesium; Modeling; Morbidity - disease rate; Myofibroblast; Nitric Oxide; Operative Surgical Procedures; Oxidative Stress; Patients; Pharmaceutical Preparations; Physiological; Predisposition; Prevalence; Risk; Series; Smooth Muscle Myocytes; Stenosis; Stents; Structure; Technology; Thrombosis; Time; Toxic effect; Uremia; Vasodilator Agents; Veins; Venous; base; design; economic cost; hemodynamics; improved; in vivo; innovation; innovative technologies; novel; prevent; prophylactic; research study; shear stress; standard of care

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.

描述（由申请人提供）：虽然动静脉瘘 (AVF) 是透析血管通路的首选模式，但超过 50% 的瘘管未能“成熟”，因为它们没有形成足够的血流量或直径来支持血液透析。这导致非常显着的临床发病率和经济成本。在发病机制层面，AVF 成熟失败是由于 (a) 小血管 (b) “不良”血流动力学，不允许释放血管舒张剂分子，如一氧化氮，以及 (c) 由于尿毒症和氧化应激导致的血管生物学异常。该提案的中心假设是，在 AV 瘘管形成时放置可延展、涂层（药物/细胞/基因/化学物质）、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，以及 (c) 由于涂层药物而改善“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 的体内降解曲线和毒性 (b) 体内原理实验证明，以记录流量和直径方面的功效。我们相信，对于可能促进 AV 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 的概念可以显着降低与 AVF 成熟失败相关的巨大临床发病率和经济成本。