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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.

冠状动脉旁路移植术（CABG）后隐静脉移植失败是一个重要的临床问题。