SBIR Phase II: Shape memory polymer AAA Endograft

该SBIR II期项目旨在继续开发新型覆膜支架，用于使用独特和专有的形状记忆聚合物（SMP）技术经皮治疗腹主动脉瘤（AAA）。腹主动脉瘤在老年人群中既常见又致命，影响7%至13%的老年人（60岁），仅在美国每年就有13，000至18，000例死亡，随着诊断技术的改进和人口老龄化，诊断患病率增加。使用覆膜不锈钢或镍钛合金覆膜支架进行血管内治疗目前是AAA治疗的首选。然而，目前的装置远非完美，并且来自腔内修复术的并发症，例如内漏、动脉瘤的持续生长、装置迁移、动脉夹层和其他问题以非常高的发生率（25-35%）持续存在。大多数（如果不是全部）这些问题可以追溯到当前设备中使用的材料的固有局限性。我们建议继续开展极具前景的I期工作，特别关注四个领域：最终确定聚合物配方;开发制造患者特定覆膜支架设计的方法;最终确定生物相容性评价;以及在急性和慢性动物研究中评价覆膜支架。II期项目结束时的预期可交付成果是特别适用于覆膜支架的最终聚合物配方、完整的ISO 109993生物相容性评价、制造患者特定覆膜支架的方法以及关于形状记忆聚合物覆膜支架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使用具有可为患者定制的特性的先进材料开发下一代医疗器械。从这种技术成功开发有用的装置应该为大量的商业机会铺平道路，包括组织工程应用，由此新组织或器官的“种子”可以被并入形状记忆聚合物装置中，并使用微创方法递送到目标部位，以最终生长健康组织。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）相融合的能力，有望开辟在手术室内创建患者专用设备的令人兴奋的前景;一旦制造完成，可以在原位将设备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对美国第13大死亡原因的疾病产生直接影响，从而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.