Vascular Grafts for Needle Free Dialysis Access Devices.

描述(由申请人提供)：这项第一阶段SBIR建议的目标是评估一种新的血管移植物设计，用作新的无针接入端口的动静脉(AV)移植物组件。意义：血液透析患者几乎每天都需要用大针头进行痛苦的血管穿刺术。这降低了生活质量，反复的组织损伤使维持可靠的长期通道变得困难。动静脉移植物(对于40%无法维持自体瘘管的患者来说是最安全的选择)容易在静脉吻合口形成血栓和其他与针创伤相关的并发症，如感染和血肿。一种可以绕过与针扎相关的问题并提供患者友好的长期血管通道且并发症发生率较低的设备将产生重大影响。创新：Starport是一种正在开发中的新的经皮血液透析端口，它提供了通向房室移植物内部的钝性插管。它在组织界面使用Healionics公司专有的STAR(R)生物材料，以克服出口部位感染问题，这一问题阻碍了早先将类似端口设备商业化的尝试。STAR的球形模板结构具有精确尺寸的微孔，优化后可促进毛细血管生长，最大限度地减少纤维包裹，并促进人体对生物膜的天然防御。成功的STARPORT还必须克服吻合口血栓问题，这一问题尤其具有挑战性，因为组织锚定的STARPORT将导致增殖的压力传递到静脉吻合口。我们建议测试“星形移植物”(一种由星形生物材料制成的血管移植物)作为STARPORT的AV组件。STAR的优化的孔结构利用了狭窄的孔大小的“甜蜜点”，孔的开口是允许血管向内生长的最小尺寸，非常适合促进抗血栓的血液流动表面。与现有的移植物材料相比，其出色的生物相容性也将在移植物-静脉吻合口形成更顺畅的过渡，潜在地减少新生内膜的增生。星形移植物还具有移植物外部的星形生物界面，以抵御感染。方法：将在绵羊模型中实现的第一阶段目标里程碑是：1)组织学证据表明，与对照ePTFE移植物相比，STAR移植物(通过移植物中间连接到STARPORT)减少了新生内膜增生，以及2)证明STAR移植物延长了装置的功能通畅性。第二阶段将解决详细的设备测试和透析设备寿命和功能的临床前演示，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.