Preclinical testing of a 3D printed external scaffold device to prevent vein graft failure after coronary bypass graft surgery

3D 打印外部支架装置预防冠状动脉搭桥手术后静脉移植失败的临床前测试

基本信息

批准号：
10385132
负责人：
Alison L Marsden
金额：
$ 34.51万
依托单位：
BIOGRAFT, INC.
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-15 至 2024-09-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10385132
关键词：
3-Dimensional 3D Print Address Animal Model Animal Testing Animals Bilateral Biocompatible Materials Biomedical Engineering Caliber Cardiac Chronic Clinical Clinical Research Collaborations Contralateral Coronary Arteriosclerosis Coronary Artery Bypass Coronary Circulation Coronary Vessels Data Data Analyses Data Set Development Device Designs Devices Diffuse Disease Doctor of Medicine Doctor of Philosophy Engineering Failure Follow-Up Studies Foundations Funding Generations Goals Gold Harvest Heart Histopathology Human Immunohistochemistry Implant In Vitro International Investments Lead Mechanics Medical Device Medical Device Designs Methods Modeling Morbidity - disease rate Operative Surgical Procedures Outcome Patients Performance Pharmacology Phase Positioning Attribute Postoperative Period Preclinical Testing Prevention Printing Procedures Regulatory Pathway Research Research Personnel Safety Saphenous Vein Secure Sheep Small Business Technology Transfer Research Stenosis Stimulus Stress Surgeon Surgical Management Techniques Testing Time Tissues Variant Vein graft base biodegradable scaffold clinical practice commercialization design elastomeric first-in-human follow-up graft failure hemodynamics human study immunogenic improved in vivo in vivo evaluation mechanical load mechanical stimulus mortality multimodal data next generation novel pre-clinical preclinical study preservation pressure prevent professor prototype response scaffold sheep model standard care success

项目摘要

Saphenous vein graft (SVG) failure following coronary artery bypass grafting (CABG) is a critical clinical problem, with recent studies revealing that as many as 25% of vein grafts develop stenosis within 12-18 months after surgery, and up to 50% of grafts occlude within 5-10 years. CABG surgery is the gold standard treatment for patients with severe multi-vessel disease, with over 370,000 procedures performed annually in the U.S. and SVGs are used in 95% of cases. Identification of strategies and devices to prevent SVG failure represents a pressing unmet clinical need. BioGraft will address this unmet need by developing an external biodegradable scaffold device to prevent SVG failure. It is well established that mechanical loading contributes to the cellular and structural changes leading to SVG failure. In current clinical practice, when the SVG is harvested and implanted into the coronary circulation, it is subjected to an abrupt change in mechanical loading (20X change in pressure, 4X change in flow-induced shear), triggering SVG wall remodeling and, often, maladaptation and failure. Our foundational R01-funded research, which laid the scientific foundation for the founding of BioGraft, showed that gradual increases in loading could mitigate or even eliminate graft failure. We demonstrated this concept in vivo, showing more favorable graft adaptation with a first-generation design in an ovine model. Here, to achieve a design that can be manufactured at scale, we propose a next-generation 3D printed biodegradable scaffold, which we will refine and test in this proposal. To achieve our goals, we propose three specific aims. In Aim 1, we will screen 3D-printed design candidates with ex vivo testing and degradation studies. This will allow us to efficiently and inexpensively select designs matching desired targets. In Aim 2, we will perform pre-clinical testing of the scaffold device in an established ovine carotid-jugular interpositional vein graft model of CABG surgery. This will establish preliminary safety and efficacy. In Aim 3, we will characterize device performance using mechanical testing and histopathology. These data will enable follow up fundraising, development of a commercialization plan and initiation of FDA discussions. BioGraft’s founding team leverages a long-standing engineering and clinical collaboration and recent partnerships with renowned investigators at Stanford and Duke who hold IP for unique bioabsorbable materials and bring expertise in rapid 3D printing manufacturing methods. We see a potential annual $1.6B total addressable market for the proposed device.

冠状动脉搭桥术（CABG）后隐静脉移植（SVG）衰竭是一个关键的临床问题，最近的研究表明，多达25％的静脉移植物在12-18个月内发展手术，最多50％的移植物在5 - 10年内阻塞。 CABG手术是黄金标准治疗患有严重多血管疾病的患者，每年在美国进行370,000多次手术 SVG在95％的病例中使用。识别防止SVG失败的策略和设备代表迫使未满足的临床需求。生物移植将通过开发外部生物降解来满足这种未满足的需求脚手架设备可防止SVG故障。众所周知，机械负荷有助于细胞以及导致SVG失败的结构变化。在当前的临床实践中，收获SVG并植入冠状动脉循环中，它发生了机械载荷的突然变化（20倍变化在压力下，流动诱导的剪切）发生了4倍），触发SVG壁重塑，并且通常不适当失败。我们的基础R01资助的研究奠定了生物移植建立的科学基础，表明，加载的成绩增加可能会减轻甚至消除等级失败。我们证明了这一点体内概念，在卵巢模型中使用第一代设计显示出更有利的移植适应。这里，为了实现可以大规模制造的设计，我们提出了下一代3D印刷生物降解的设计脚手架，我们将在此提案中进行完善和测试。为了实现我们的目标，我们提出了三个具体目标。 AIM 1，我们将通过体内测试和降解研究筛选3D打印的设计候选。这将允许我们有效且廉价地选择匹配所需目标的设计。在AIM 2中，我们将执行临床前在已建立的卵子颈动脉 - 朱吉尔插入性静脉移植模型中测试脚手架装置的测试外科手术。这将建立初步的安全性和效率。在AIM 3中，我们将表征设备性能使用机械测试和组织病理学。这些数据将实现后续筹款，开发 FDA讨论的商业化计划和倡议。 Biograft的创始团队利用了一个长期的工程和临床合作以及与斯坦福大学和杜克大学著名调查员的最新合作伙伴关系谁持有IP的独特生物吸附材料，并在快速3D打印制造方法中带来了专业知识。我们看到该拟议设备的潜在年度$ 1.6B总可寻址市场。