Vascular Grafts for Needle Free Dialysis Access Devices.

描述（由申请人提供）：本I期SBIR提案的目的是评价一种新型血管移植物设计，用作新型无针输液港的动静脉（AV）移植物组件。意义：血液透析患者几乎每天都需要使用大针头进行痛苦的血管穿刺。这影响了生活质量，并且反复的组织创伤使得难以维持可靠的长期通路。AV移植物（对于40%无法维持自体瘘的患者来说是最安全的选择）易于在静脉吻合处形成血栓和其他针创伤相关并发症，如感染和血肿。一种能够避免与针刺相关的问题并提供患者友好的长期血管通路且并发症发生率低的器械将产生重大影响。创新：STARport是一种正在开发的新型经皮血液透析输液港，可提供钝性插管进入AV移植物内部。它在组织界面处使用Healionics专有的星星（R）生物材料，以克服出口部位感染问题，该问题阻碍了早期将类似端口设备商业化的尝试。星星的球形模板结构具有精确尺寸的微孔，优化以促进毛细血管向内生长，最大限度地减少纤维化包裹，并促进身体对生物膜的天然防御。成功的STAR端口还必须克服吻合口血栓形成问题，这一问题尤其具有挑战性，因为组织锚定端口将增生诱导应力传递到静脉吻合口。我们建议将“STARgraft”（一种由星星生物材料制成的血管移植物）作为STARport的AV组件进行试验。星星的优化孔结构，利用了一个狭窄的孔径“甜蜜点”，其中孔开口是允许血管向内生长的最小尺寸，是理想的适合于促进抗血栓血流表面。其卓越的生物相容性也应该比现有的移植物材料在移植物-静脉吻合处产生更平滑的过渡，从而潜在地减少新生内膜增生。STARgraft还具有移植物外部的星星生物界面以抵抗感染。方法：第一阶段目标里程碑--将在绵羊模型中实现--是：1）组织学证据表明，与对照ePTFE移植物相比，STARgraft（移植物中部连接至STARport）减少了新生内膜增生，以及2）证明STARgraft延长了功能性通畅性器械。第II阶段将解决详细的器械测试和器械寿命的临床前证明以及透析功能，作为临床早期可行性研究的先决条件。

DESCRIPTION (provided by applicant): The objective of this Phase I SBIR proposal is to evaluate a novel vascular graft design for use as the arteriovenous (AV) graft component of a new needle-free access port. Significance: Hemodialysis patients require painful punctures with large needles for vascular access on a near-daily basis. This worsens quality of life, and the repeated tissue trauma makes maintenance of a reliable long-term access difficult. AV grafts (the safest option for the 40% of patients unable to sustain an autogenous fistula) are prone to thrombosis at the venous anastomosis and other needle-trauma-related complications such as infection and hematoma. A device that could circumvent the issues associated with needlesticks and provide patient- friendly long-term vascular access with low complication rate would have major impact. Innovation: STARport is a new percutaneous hemodialysis port under development that provides blunt cannula access to the inside of an AV graft. It uses Healionics' proprietary STAR(R) biomaterial at the tissue interface to overcome the exit site infection issue that stymied earlier attempts to commercialize similar port devices. STAR's sphere-templated structure has precisely-dimensioned microporosity optimized to promote capillary ingrowth, minimize fibrotic encapsulation, and facilitate the body's natural defenses against biofilm. A successful STARport must also overcome the anastomotic thrombosis issue, made especially challenging because the tissue-anchored port transmits hyperplasia-inducing stresses to the venous anastomosis. We propose to test "STARgraft" (a vascular graft made from STAR biomaterial) as the AV component for STARport. STAR's optimized pore structure, which takes advantage of a narrow pore size "sweet spot" where pore openings are the minimum size permitting vascular ingrowth, is ideally suited for promoting a thromboresistant bloodflow surface. Its exceptional biocompatibility should also create a smoother transition at the graft- vein anastomosis than existing graft materials, potentially reducing neointimal hyperplasia. STARgraft also features the STAR biointerface on the exterior of the graft to resist infection. Approach: The Phase I target milestones - to be achieved in a sheep model - are: 1) histological evidence that STARgraft (with midgraft connection to STARport) reduces neointimal hyperplasia compared to control ePTFE grafts, and 2) demonstration that STARgraft extends the functional patency of the device. A Phase II would address detailed device testing and preclinical demonstration of device longevity and function for dialysis as prerequisites for a clinical Early Feasibility Study.