Biointegrating Dialysis Access Graft with Self Stabilizing Flow

具有自稳定流的生物整合透析通路移植物

• 批准号: 9048990
• 负责人: Andrew Marshall
• 金额: $ 58.11万
• 依托单位: HEALIONICS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-04 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9048990
• 关键词: Anastomosis - action; Arteriovenous fistula; Biocompatible Materials; Blood Circulation; Blood Vessels; Caliber; Cannulations; Cardiac; Catheters; Cessation of life; Clinical; Coupled; Development; Devices; Dialysis patients; Dialysis procedure; End stage renal failure; Equilibrium; Failure; Feasibility Studies; Feedback; Foreign Bodies; Freedom; Frequencies; Goals; Hemodialysis; Human; Hyperplasia; Implant; Infection; Intervention; Lead; Lesion; Life; Maintenance; Mechanics; Medical; Methods; Modeling; Motion; Needles; Operative Surgical Procedures; Outcome; Particulate; Pathologic; Patients; Pattern; Performance; Phase; Physiologic pulse; Plant Roots; Prosthesis; Pulmonary Embolism; Qualifying; Recommendation; Recurrence; Research; Resistance; Resort; Risk; Safety; Sheep; Silicones; Small Business Innovation Research Grant; Stenosis; Stress; Structure; Surface; Testing; Thrombosis; Time; Tissues; Trauma; Ultrasonography; Vascular Graft; Veins; Venous; base; capsule; constriction; design; graft function; hemodynamics; high risk; improved; innovation; novel; patient population; pressure; prevent; public health relevance; research and development; research clinical testing; shear stress; success

 DESCRIPTION (provided by applicant): Objective: The goals of this Phase II SBIR proposal are to evaluate longer-term patency and safety of a novel hemodialysis access graft design (ePTFE treated with textured microporous silicone exterior layer) and complete the necessary development steps to prepare the device for clinical evaluation. The Phase I feasibility study demonstrated markedly superior patency and reduction of neointimal hyperplasia compared to untreated ePTFE controls through 12 weeks in a sheep model. Significance: The need for frequent treatments (at least 3x per week) makes maintenance of reliable vascular access for hemodialysis patients extremely challenging. As a result of high maturation failure in autogenous arteriovenous (AV) fistulas (the preferred vascular access option) and a reluctance to use AV grafts (the safest alternative) due to longer-term patency concerns, more than half of all first-year hemodialysis patients, and more than 20% longer term, are treated via unsafe "last-resort" infection-prone catheters. Loss of patency by AV grafts is primarily due to development of neointimal hyperplasia at the venous anastomosis, which causes progressive narrowing of the lumen, leading to unstable low flow followed by thrombosis failure. Successful clinical introduction of an AV graft overcoming the hyperplasia problem would increase access options, and especially, enable a significant reduction in the use of high-risk catheters. Innovation: A number of factors, including surgical trauma at time of implant, graft-vein compliance mismatch, and unfavorable hemodynamic shear stress patterns are known to contribute to neointimal hyperplasia. But the underlying root cause of the problem that causes synthetic AV grafts to fail is the self-reinforcing "death spiral" feedback loop (hyperplasia causes low flow, which upregulates the advance of hyperplasia). By treating ePTFE grafts with an exterior biointerface that prevents the formation of a fibrous perigraft tissue capsule, the usual mechanical constriction effects are eliminated. The retained natural dynamic compliance of the perigraft tissue permits greater freedom for elastic and vibratory motion of the graft wall. This reduces compliance mismatch and provides more favorable stress conditions at the ePTFE-neointima interface. It also changes the usual flow effect of hyperplasia. An increase in stenotic resistance is compensated via a mechanism that widens the upstream hydraulic diameter. This appears to replace the pathologic feedback loop with a more favorable self-stabilizing feedback loop. The promising Phase I results suggest that this approach can lead to a major leap in AV graft clinical performance and reliability. Approach: Specific aims are 1) evaluating long-term patency, 2) demonstrating cannulation safety, and 3) completing requisite function and reliability testing. The proposed R&D steps will support a subsequent IDE application for a First-In-Human Early Feasibility Study for this Class II device. Project success would offer a safer and more reliable treatment option for a large fraction of the dialysis patient population.

 描述（由申请人提供）：目的：本II期SBIR提案的目的是评价新型血液透析通路移植物设计（采用毛面微孔硅胶外层处理的ePTFE）的长期通畅性和安全性，并完成必要的开发步骤以准备器械进行临床评价。I期可行性研究证明，在绵羊模型中，12周内，与未处理的ePTFE对照相比，通畅性明显上级，新生内膜增生减少。重要性：由于需要频繁治疗（每周至少3次），因此为血液透析患者维持可靠的血管通路极具挑战性。由于自体动静脉（AV）瘘（首选血管通路选择）的高度成熟失败以及由于长期通畅性问题而不愿使用AV移植物（最安全的替代方案），超过一半的第一年血液透析患者和超过20%的长期血液透析患者通过不安全的“最后手段”易感染导管进行治疗。AV移植物的通畅性丧失主要是由于静脉吻合处新生内膜增生的发展，这导致管腔进行性狭窄，导致不稳定的低流量，随后是血栓形成失败。成功临床引入AV移植物克服增生问题将增加入路选择，特别是能够显著减少高风险导管的使用。创新：许多因素，包括植入时的手术创伤、移植物-静脉顺应性不匹配和不利的血流动力学剪切应力模式，已知会导致新生内膜增生。但是，导致合成AV移植失败的问题的根本原因是自我强化的“死亡螺旋”反馈回路（增生导致低流量，这会上调增生的进展）。通过使用外部生物界面处理ePTFE移植物，防止纤维移植物周围组织囊的形成，消除了通常的机械收缩效应。移植物周围组织的保留的自然动态顺应性允许移植物壁的弹性和振动运动的更大自由度。这减少了顺应性不匹配，并在ePTFE-新生内膜界面处提供了更有利的应力条件。它还改变了增生的通常流动效果。狭窄阻力增加 通过扩大上游水力直径的机制进行补偿。这似乎用更有利的自稳定反馈循环取代了病理反馈循环。有希望的I期结果表明，这种方法可以导致AV移植物临床性能和可靠性的重大飞跃。方法：具体目的是1）评价长期通畅性，2）证明插管安全性，3）完成必要的功能和可靠性试验。拟议的研发步骤将支持该II类器械首次人体早期可行性研究的后续IDE申请。项目的成功将为大部分透析患者提供更安全、更可靠的治疗选择。