SBIR Phase II: Shape memory polymer AAA Endograft

该SBIR第二阶段项目旨在利用独特的专有形状记忆聚合物(SMP)技术，继续开发用于经皮治疗腹主动脉瘤(AAA)的新型内移植物。腹主动脉瘤在老年人中既常见又致命，影响到7%至13%的老年人(60岁)，仅在美国每年就有1.3万至1.8万人死亡，随着诊断技术的进步和人口老龄化，诊断患病率不断上升。使用覆膜不锈钢或镍钛合金支架的血管内治疗现在是AAA治疗的首选选择。然而，目前的设备还远远不是完美的，血管内修复的并发症，如内漏、动脉瘤的持续生长、设备移位、动脉夹层和其他问题，仍然以非常高的比率(25%-35%)存在。这些问题中的大多数(如果不是全部的话)可以追溯到当前设备中使用的材料的固有限制。我们建议继续开展前景看好的第一阶段工作，特别关注四个领域：最终确定聚合物配方；开发制造针对患者的内移植物设计的方法；完成生物相容性评估；以及在急慢性动物研究中评估内移植物。第二阶段项目结束时的预期成果包括特别适用于内移植物的最终聚合物配方、完整的国际标准化组织109993生物兼容性评估、特定于患者的内移植物的制造方法，以及关于形状记忆聚合物内移植物急性和慢性血管反应的全面数据。这项工作的更广泛影响在于开发使用先进材料的下一代医疗设备，这些材料具有可以为患者定制的特性。从这类技术中成功开发出有用的设备应该会为包括组织工程应用在内的大量商业机会铺平道路，在这种应用中，新组织或器官的“种子”可以被结合到形状记忆聚合物设备中，并使用微创方法输送到目标部位，最终生长出健康的组织。将形状记忆聚合物技术与先进的三维成像和自动化制造方法(如快速成型和立体光刻)融合在一起的能力，有望开启在手术套件中创建针对患者的设备的令人兴奋的前景；一旦制造出来，设备可以就地压缩成导管，并立即输送到患者体内。最后，整个项目的成功完成应该会对一种疾病产生立竿见影的影响，这种疾病是美国第13大死亡原因，因此也会对人类健康产生影响。

This SBIR Phase II project aims to continue the development of novel endografts for percutaneous treatment of abdominal aortic aneurysms (AAA) using unique and proprietary shape memory polymer (SMP) technology. Abdominal aortic aneurysms are both common and lethal in the older population, affecting between 7 and 13 % of older persons ( 60 years), accounting for between 13,000 and 18,000 deaths per year in the US alone, and increasing in diagnostic prevalence as both diagnostic techniques improve and the population ages. Endovascular treatment using covered stainless steel or Nitinol stent-grafts is now the preferred option for AAA treatment. However, current devices are far from perfect, and complications from endovascular repair such as endoleaks, continued growth of the aneurysm, device migration, arterial dissections, and other problems persist at very high ( 25-35%) rates. Most if not all these problems can be traced to the inherent limitations of the materials used in current devices. We propose to continue the highly promising Phase I work with particular focus on four areas: finalize polymer formulation; develop methods to manufacture patient-specific endograft designs; finalize biocompatibility evaluation; and evaluate endografts in acute and chronic animal studies. Anticipated deliverables at the end of the Phase II project are a finalized polymer formulation particularly suitable for endografts, complete ISO 109993 biocompatibility evaluation, methods to manufacture patient-specific endografts, and comprehensive data on the acute and chronic vascular response of the shape memory polymer endografts. The broader impacts of this work lie in the development of the next generation of medical devices using advanced materials with characteristics that can be customized to the patient. The successful development of useful devices from such technologies should pave the way for a plethora of commercial opportunities including tissue-engineering applications whereby the "seeds' of new tissues or organs can be incorporated into shape memory polymer devices and delivered using minimally invasive methods into the target site to eventually grow healthy tissue. The ability to fuse shape memory polymer technology with advanced three-dimensional imaging and automated manufacturing methods, such as rapid prototyping and stereo-lithography, promises to open up the exciting prospect of creating patient-specific devices within the operating suite; devices that once manufactured can be compacted in situ into a catheter and delivered immediately into the patient. Lastly, successful completion of the overall project should have immediate impact on a disease that is the 13th leading cause of death in the US, and consequently on human health.