Infection and Thrombosis Resistant Needle-Free Hemodialysis Access Port and Graft Using STAR Biomaterials

 描述（由申请人提供）：目的：本直接进入II期SBIR项目的目标是推进无针血液透析输液港器械的开发。该项目源于一种新型血管移植物结构的可行性结果（I期等效），该结构显示出上级通畅性和抗感染性，结合先前授予的II期资助证明的出口部位感染控制性能。重要性：血液透析患者每周需要用大针头穿刺数次，以进入血管，最常见的是进入手术创建的动静脉（AV）瘘。这影响了生活质量，并且组织创伤相关问题（如感染和血肿）使得难以维持可靠的长期入路。对于30 - 40%无法维持瘘管的患者，人工AV移植物提供了最安全的选择。然而，这些移植物易于在静脉吻合处血栓形成，并且针创伤相关并发症由于移植物的进行性损伤和易形成生物膜的外来生物材料的存在而恶化。一种可以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移植物管腔。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，这些问题限制了早期将类似端口器械商业化的尝试。星星生物材料具有优化的微孔结构，证明可促进毛细血管向内生长，最大限度地减少纤维化包裹，并增强身体对细菌生物膜发展的天然防御。为了使STARport具有高影响力，它还必须克服人工AV移植物的问题。一项基于STAR的新型AV移植物构建的体内可行性研究显示了显著的结果。与标准ePTFE对照相比，通过完全抑制移植物外部周围的组织囊收缩实现了上级通畅性。与大多数方法（试图最大限度地减少新生内膜增生）不同，抑制纤维化囊的“蟒蛇挤压”效应是一种新的创新方法，似乎可以恢复身体在新生内膜增生和流动之间的自然平衡。同样值得注意的是，"STARgraft"还显示出对细菌定植的显著改善的抗性。方法：具体目的是证明1）长期移植物通畅性，和2）透析通路功能、安全性和可靠性。拟议的研发解决了人类使用IDE批准所需的关键知识差距。项目的成功将为透析患者提供更好的生活质量选择，也将促进向家庭透析治疗的过渡，显著减轻医疗保健系统的经济负担。

 DESCRIPTION (provided by applicant): Objective: The goal of this Direct-to-Phase II SBIR project is to advance development of a needle-free hemodialysis access port device. The project stems from promising (Phase I equivalent) feasibility results with a novel vascular graft construct showing superior patency and resistance to infection, combined with exit site infection control performance demonstrated under a previously awarded Phase II grant. Significance: Hemodialysis patients require punctures with large needles several times a week for vascular access, most often into surgically created arteriovenous (AV) fistulas. This worsens quality of life, and tissue trauma-related issues such as infection and hematoma makes maintenance of a reliable long-term access difficult. For the 30-40% of patients unable to sustain a fistula, prosthetic AV grafts provide the safest option. However, these grafts are prone to thrombosis at the venous anastomosis, and needle trauma-related complications are worsened by the progressive damage to the grafts and the presence of a biofilm-prone foreign biomaterial. A device that could circumvent the issues associated with needle sticks and provide patient-friendly long-term vascular access with low complication rates would have a major impact. Innovation: STARport is a new percutaneous hemodialysis port under development that provides blunt cannula access into the lumen of an AV graft. It uses Healionics' proprietary STAR(r) biomaterial at the tissue interfaces to overcome the exit site infection issues that limite earlier attempts to commercialize similar port devices. STAR biomaterial has an optimized microporous structure demonstrated to promote capillary ingrowth, minimize fibrotic encapsulation, and enhance the body's natural defenses against bacterial biofilm development. For a STARport to have high impact, it must also overcome the prosthetic AV graft issues. An in vivo feasibility study with a new STAR-based AV graft construction showed a remarkable outcome. Superior patency vs. standard ePTFE controls was achieved by the complete inhibition of tissue capsular contraction around the graft exterior. Unlike most approaches (which attempt to minimize neointimal hyperplasia), suppressing the "anaconda squeeze" effect of the fibrotic capsule is a fresh and innovative approach that appears to restore the body's natural balance between neointimal hyperplasia and flow. Equally remarkable, the "STARgraft" also showed dramatically improved resistance to bacterial colonization. Approach: Specific aims are demonstrating 1) long-term graft patency, and 2) dialysis access function, safety and reliability. The proposed R&D addresses the critical knowledge gaps needed to proceed toward IDE approval for human use. Project success will offer an improved quality-of-life option for dialysis patients, and it will also facilitate transitions to home dialysis treatment, significantl reducing the economic burden to the healthcare system.