Nanotechnology for Magnetic Endothelialization of Implantable Cardiovascular Devices

用于植入式心血管装置的磁性内皮化的纳米技术

基本信息

批准号：
9980974
负责人：
Brandon J Tefft
金额：
$ 24.26万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-18 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9980974
关键词：
Address Adverse reactions Animal Model Animals Autologous Award Biocompatible Materials Biological Biology Biomedical Engineering Blood Blood Vessels Bypass Cardiac Catheterization Procedures Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cell Adhesion Cells Clinic Clinical Coagulation Process Collaborations Communication Research Core Facility Data Analyses Department chair Development Devices Doctor of Medicine Doctor of Philosophy Electrospinning Endothelial Cells Endothelium Engineering Exhibits Exposure to Extracellular Matrix Extramural Activities Faculty Family suidae Fiber Funding Future Generations Glass Goals Heart Valves Histology Hyperplasia Implant In Vitro Label Laboratories Magnetic nanoparticles Magnetism Mechanics Mediating Medical Device Medicine Mentors Methods Microscopy Minnesota Modeling Molecular Biology Nanotechnology Outcome Patient Care Patient Education Patients Pharmaceutical Preparations Physicians Polyurethanes Positioning Attribute Postdoctoral Fellow Property Prosthesis Proteins Regenerative Medicine Research Research Personnel Research Project Grants Research Support Resources Safety Schools Science Scientist Series Services Sheep Stents Structure Surface Techniques Testing Thick Thrombosis Thrombus Tissue Engineering Training Translational Research Universities Vascular Endothelium Vascular Graft Work adverse outcome animal facility biomaterial compatibility calcification cardiac tissue engineering career career development clinical center clinical translation clinically relevant college design education research engineering design experience implant compatibility implantation improved improved outcome innovation interest iron oxide nanoparticle medical implant nanofiber new technology next generation novel novel strategies patient population patient safety post-doctoral training programs prototype research facility responsible research conduct risk minimization skills statistics superparamagnetism targeted delivery tenure track thrombogenesis

项目摘要

DESCRIPTION (provided by applicant):Project(Summary/Abstract The candidate holds a Ph.D. in Biomedical Engineering from Northwestern University and is currently a Research Associate at Mayo Clinic. His research interests are in the field of cardiovascular tissue engineering. His graduate thesis work involved a molecular biology approach for improving endothelial cell retention to vascular grafts. This led to his postdoctoral work which involves an engineering approach for improving capture and retention of endothelial cells to vascular stents and grafts. His postdoctoral work also involves a tissue engineered cardiac valve project to explore both biological and biosynthetic approaches. The candidate's immediate career goal is to transition from mentored to independent research by completing his postdoctoral training and beginning a tenure track faculty position at a major research university. This will require focusing his current projects into a novel research direction while also receiving additional training that will be needed to successfully complete the current and future projects as an independent investigator. The K99/R00 mechanism is the ideal means of achieving this goal. The candidate's long term career goal is to establish an independent and extramurally funded research program within the field of cardiovascular tissue engineering in order to meaningfully improve patient care and train the next generation of scientists, physicians, and engineers. Research career development during the award will include working with an interdisciplinary mentoring team of clinicians, scientists, and engineers. The candidate's primary mentor, Dr. Amir Lerman, M.D., is the Chair of Cardiovascular Research at Mayo Clinic and provides expertise in endothelial cell and vascular biology. The candidate's co-mentors are Dr. Gurpreet Sandhu, M.D., Ph.D. who is the Chair of the Cardiac Catheterization Laboratory at Mayo Clinic and provides expertise in clinical device prototype design and testing, Dr. Dan Dragomir-Daescu, Ph.D. who is a principal engineer at Mayo Clinic and provides expertise in engineering design and analysis, and Dr. Robert Tranquillo, Ph.D. who is Chair of the Department of Biomedical Engineering at the University of Minnesota and provides expertise in biomedical engineering and cardiovascular tissue engineering. Working with his mentors, the candidate will train in clinical device prototype design, porcine model analysis of novel vascular grafts, ovine model analysis of novel cardiac valves, advanced magnetic nanoparticle synthesis, and advanced electrospinning techniques. The candidate will also train in other essential skills including responsible conduct of research, grantsmanship, communication of research findings, mentoring, and project management. Finally, educational opportunities such a graduate coursework in regenerative medicine, cardiovascular physiology, data analysis, and statistics as well as various research and clinical seminar series will round out the training experience. Mayo Clinic offers a variety of educational and support services through the Graduate School, College of Medicine, Office of Research Education, and Center for Clinical and Translation Science that will facilitate the necessary training. Mayo Clinic is committed to supporting translational research and recently established the Center for Regenerative Medicine as a strategic initiative. World experts in a variety of fields are available for collaboration with th common goal of improving patient care. Mayo also offers a variety of research resources and facilities including core facilities such as the Microscopy and Cell Analysis Core, the Biostatistis Core, the Histology Core, and the Materials and Structural Testing Core. The Division of Engineering features a full machine shop, electrical shop, and glass blowing shop to support research requests for engineering design and development. Mayo also has several animal facilities including the Cardiovascular Innovation Laboratory which features a full cardiac catheterization laboratory dedicated for animal studies. The proposed research project is a natural extension of the candidate's ongoing work that focuses his research in a novel direction to begin the transition to independence. The proposed work addresses the important clinical need of improving the blood compatibility of implanted cardiovascular devices by advancing the magnetic endothelialization approach. The proposed work will develop the next generation of magnetic grafts by using the electrospinning fabrication method to generate magnetic nanofiber biomaterials. The grafts will be tested for mechanical, magnetic, and thrombogenicity properties in vitro. The grafts will then be tested for clinicallyOrelevant outcomes including patency, thrombus formation, and neointimal hyperplasia in a porcine implantation model. These grafts are expected to be an important step in the development towards clinical translation. The proposed work will also develop a novel magnetically-functionalized and aligned nanofiber biomaterial that is optimized for mechanical and magnetic properties. This biomaterial is expected to have a wide range of important applications for targeted delivery of cells, drugs, and proteins. The proposed work will then use a novel biomaterial to fabricate novel cardiac valves capable of magnetic endothelialization. The valves will be tested for mechanical, magnetic, and thrombogenic properties in vitro. The valves will then be tested for clinically-relevant outcomes including function, thrombus formation, and calcification in an ovine implantation model. These valves are expected to demonstrate proof of concept for magnetic endothelialization of valves.

描述（由适用提供）：项目（摘要/摘要候选人拥有西北大学的生物医学工程博士学位改善对血管支架和移植物的内皮细胞捕获和保留的工程方法。他的博士后工作还涉及组织工程的心脏瓣膜项目，以探索生物学和生物合成方法。候选人的直接职业目标是通过完成博士后培训，并在一所主要的研究大学开始任职期间的职位，从指导到独立研究。这将需要将他当前的项目集中在一个新颖的研究方向上，同时还需要接受其他培训，以成功完成当前和未来的项目作为独立研究者。 K99/R00机制是实现这一目标的理想手段。候选人的长期职业目标是在心血管组织工程领域建立一个独立的和外部资助的研究计划，以便有意义地改善患者护理并培训下一代科学家，医生和工程师。该奖项期间的研究职业发展将包括与临床医生，科学家和工程师的跨学科指导团队合作。候选人的主要导师，医学博士Amir Lerman博士是Mayo Clinic心血管研究的主席，并提供内皮细胞和血管生物学方面的专业知识。候选人的联合会是医学博士Gurpreet Sandhu博士。他是Mayo Clinic心脏导管实验室的主席，并提供临床设备原型设计和测试的专业知识，Dan Dragomir-Daescu博士，博士学位。他是Mayo Clinic的主要工程师，并提供工程设计和分析方面的专业知识，以及Robert Tranquillo博士博士。他是明尼苏达大学生物医学工程系主席，并提供生物医学工程和心血管组织工程的专业知识。候选人与他的导师合作，将训练临床装置原型设计，新型血管移植物的猪模型分析，新颖心脏瓣膜的氧模型分析，高级磁性纳米颗粒合成和晚期电纺丝技术。候选人还将培训其他基本技能，包括负责任的研究，授予技巧，研究结果的交流，心理和项目管理。最后，诸如再生医学，心血管生理学，数据分析和统计学以及各种研究和临床精神分析系列的教育机会，例如培训经验。 Mayo Clinic通过研究生院，医学院，研究教育办公室以及临床与翻译科学中心提供各种教育和支持服务，以促进必要的培训。 Mayo Clinic致力于支持翻译研究，并最近建立了再生医学中心作为一项战略计划。各种领域的世界专家可用于协作，以改善患者护理的共同目标。梅奥还提供各种研究资源和设施，包括核心设施，例如显微镜和细胞分析核心，生物稳定核心，组织学核心以及材料和结构测试核心。工程部门设有一家完整的机械车间，电气车间和玻璃吹店，以支持工程设计和开发的研究请求。 Mayo还设有几个动物设施，包括心血管创新实验室，该实验室具有专门用于动物研究的全心脏导管实验室。拟议的研究项目是候选人正在进行的工作的自然扩展，将他的研究集中在新的方向上，开始过渡到独立性。提出的工作解决了通过推进磁性内皮化方法来改善植入心血管装置的血液兼容性的重要临床需求。提出的工作将通过使用静电纺丝制造方法来产生磁性纳米纤维生物材料，从而发展下一代的磁移植物。移植物将在体外测试机械，磁性和血栓形成性能。然后，将测试移植物在猪植入模型中的临床方面结果，包括通畅，血栓形成和新内膜增生。预计这些图形将是迈向临床翻译发展的重要一步。提出的工作还将开发出一种新型的磁功能和对齐的纳米纤维生物材料，该纳米纤维生物材料可针对机械和磁性特性进行了优化。预计该生物材料将在细胞，药物和蛋白质的靶向递送方面具有广泛的重要应用。然后，提出的工作将使用一种新型的生物材料来制造能够磁内皮化的新型心脏瓣膜。该阀将在体外测试机械，磁性和血栓形成性能。然后，将测试阀门与临床相关的结果，包括功能，血栓形成和卵巢植入模型中的计算。预计这些阀将证明阀门磁性内皮化的概念证明。