Development of a Biological Stent Graft for Aorta Aneurysm Repair

用于主动脉瘤修复的生物覆膜支架的开发

• 批准号: 7804697
• 负责人: Nicolas L'Heureux
• 金额: $ 21.49万
• 依托单位: CYTOGRAFT TISSUE ENGINEERING, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7804697
• 关键词: Actins; Adhesions; Adoption; Allogenic; Aneurysm; Angiography; Animal Model; Animals; Aorta; Aortic Aneurysm; Ascorbic Acid; Biological; Blood; Blood Vessels; Canis familiaris; Catheters; Cause of Death; Cell Line; Cells; Collagen; Data; Development; Devices; Diagnosis; EGF gene; Endothelial Cells; Evaluation; Exclusion; Extracellular Matrix; Extracellular Matrix Proteins; Extravasation; Failure; Family suidae; Feasibility Studies; Fibroblasts; Grant; Histology; Human; Implant; Industry; Inflammation; Insulin; Investigation; Life; Location; Mechanics; Modeling; Monkeys; Morphology; Motion; Neck; Operative Surgical Procedures; Patients; Performance; Perfusion; Phase; Process; Property; Recreation; Relative (related person); Research Proposals; Rupture; Sampling; Serum; Small Business Innovation Research Grant; Smooth Muscle Myocytes; Solutions; Stents; Supporting Cell; Surface; Technology; Teflon; Testing; Thick; Tissue Engineering; Tissues; Work; abdominal aorta; base; cell motility; dacron; experience; improved; in vivo; in vivo Model; macrophage; migration; prevent; public health relevance; repaired; sample fixation; standard of care; von Willebrand Factor

DESCRIPTION (provided by applicant): Abdominal aorta aneurysms (AAA) are diagnosed in more than 100,000 patients in the U.S. each year. About 70% of these patients require surgical intervention to prevent aneurysm progression. Nearly 20 years ago, Parodi revolutionized AAA treatment and repair by using an ePTFE stent graft that could be delivered via an endovascular approach. Today, more than 35,000 AAA stent grafts are placed annually, making AAA repair devices a $700 million industry in the U.S. alone. Despite the rapid adoption of endovascular repair, the devices are associated with a significant failure rate (more than 20% at one year). The majority of these failures are caused by leakage around or through the device. This type of endoleakage is caused by relative motion between the stent graft device and the native aorta. This relative motion is aggravated by the fact that the stent grafts are static devices that cannot remodel as the native aorta moves and remodels dynamically. Moreover, most stent grafts are wrapped in ePTFE (Teflon), which works well as a blood contacting surface, but does not adhere well to the surrounding tissue. We hypothesized that by replacing the ePTFE covering on a stent graft with a biological sheet, we might improve upon the fixation of the device into the native aorta. That is, by providing a natural collagen substrate which would support cell ingrowth and tissue adhesion, we would increase the bonding strength between the device and the native aorta. We termed this approach biological neck fixation. The objective of this Phase I grant is to demonstrate the initial feasibility of biological neck fixation such that we can more appropriately justify expanded efficacy studies in Phase II. Specifically, in Phase I, we will: develop a sheet built from canine cells that closely matches the mechanical properties of human sheets that we have developed previously (Specific Aim 1); implant the biological stent graft via a 10 French catheter in a canine model to evaluate durability, morphology, and histological properties (Specific Aim 2.1); and compare the adhesion and anchoring properties of biological stent grafts relative to the standard of care in a canine model (Specific Aim 2.2). Exclusion of the AAA without signs of migration or endoleakage at 3 months post-implant, and equal or greater anchoring strength relative to ePTFE stent grafts will be the key milestones to justify advancing to Phase II. The long-term objective of this project will be to commercialize a completely biological stent graft that can remodel with the host aorta, thereby reducing the overall failure rate relative to the current standard of care. PUBLIC HEALTH RELEVANCE: Abdominal aorta aneurysms (AAA) are diagnosed in more than 100,000 patients in the U.S. each year, and are the 13th leading cause of death. Today, more than 35,000 AAA endovascular stent grafts are placed annually, making AAA repair devices a $700 million industry in the U.S. alone. This Research Proposal describes a new repair device which may significantly reduce the relatively high failure rates associated with the standard of care in AAA repair.

描述（由申请人提供）：每年在美国超过100,000名患者中诊断出腹主动脉瘤（AAA）。这些患者中约有70％需要手术干预以防止动脉瘤进展。大约20年前，Parodi通过使用可以通过血管内方法进行的EPTFE支架移植物来彻底改变AAA治疗和修复。如今，每年放置超过35,000个AAA支架移植物，仅在美国就使AAA维修设备成为了7亿美元的行业。尽管血管内修复迅速采用，但这些设备仍与明显的故障率相关（一年超过20％）。这些故障的大多数是由周围或通过设备泄漏引起的。这种类型的内膜是由支架移植装置和天然主动脉之间的相对运动引起的。由于支架移植物是静态设备，因此随着天然主动脉移动并动态重塑，这种相对运动会加剧这种相对运动。此外，大多数支架移植物都包裹在EPTFE（Teflon）中，其效果很好，作为血接触表面，但不能很好地粘附在周围的组织上。我们假设，通过用生物纸代替支架移植物上的EPTFE覆盖物，我们可能会改善设备固定到天然主动脉中的固定。也就是说，通过提供一种自然胶原蛋白底物，该基材将支持细胞向内生长和组织粘附，我们将提高设备和天然主动脉之间的键合强度。我们称这种方法生物颈部固定。 I阶段I授予的目的是证明生物颈部固定的最初可行性，以便我们可以在第二阶段中更适当地证明扩大的疗效研究是合理的。具体而言，在第一阶段，我们将：开发一种由犬单元建造的纸张，与我们以前开发的人板的机械性能紧密匹配（特定的目标1）；通过10个法国导管在犬模型中植入生物支架移植物，以评估耐用性，形态和组织学特性（特定目标2.1）；并比较犬模型中相对于护理标准的生物支架移植物的粘附和锚定特性（特定的目标2.2）。在植入后3个月时，排除没有迁移或内肢迹象的AAA，相对于EPTFE支架移植物的锚固强度相等或更高的锚固强度将是证明前进到II期合理的关键里程碑。该项目的长期目标是将可以与宿主主动脉进行重塑的完全生物支架移植物进行商业化，从而降低相对于当前护理标准的总体故障率。 公共卫生相关性：腹主动脉瘤（AAA）每年在美国有100,000多名患者中被诊断出，这是第13个主要死亡原因。如今，每年放置超过35,000个AAA内血管内支架移植物，仅在美国就使AAA维修设备成为了7亿美元的行业。该研究建议描述了一种新的维修设备，该设备可能会显着降低与AAA修复中护理标准相关的相对较高的失败率。