Nanotechnology for magnetic endothelialization of implantable cardiovascular devices

用于植入式心血管装置磁性内皮化的纳米技术

• 批准号: 9107632
• 负责人: Brandon J Tefft
• 金额: $ 13.34万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-18 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9107632
• 关键词: Address; Adverse reactions; Animal Model; Animals; Autologous; Award; Biocompatible; 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; Endothelial Cells; Endothelium; Engineering; Exhibits; Extracellular Matrix; Faculty; Family suidae; Fiber; Funding; Future; Generations; Glass; Goals; Heart Valves; Histology; Hyperplasia; Implant; In Vitro; Label; Laboratories; Life; 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; Risk; Safety; Schools; Science; Scientist; Series; Services; Sheep; Stents; Structure; Surface; Techniques; Testing; Thick; Thrombosis; Thrombus; Tissue Engineering; Training; Translational Research; Translations; Universities; Vascular Endothelial Cell; Vascular Graft; Work; abstracting; adverse outcome; animal facility; calcification; career; career development; clinically relevant; college; design; education research; engineering design; experience; implant compatibility; implantation; improved; improved outcome; innovation; interest; iron oxide; nanofiber; nanoparticle; neointima formation; new technology; next generation; novel; novel strategies; patient population; patient safety; post-doctoral training; programs; prototype; research facility; responsible research conduct; skills; statistics; targeted delivery; tenure track

 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（由申请人提供）：项目（摘要/摘要）候选人拥有博士学位。他是西北大学生物医学工程专业的教授，目前是马约诊所的研究助理。 他的研究兴趣是心血管组织工程领域。 他的研究生论文工作涉及改善血管移植物内皮细胞保留的分子生物学方法。 这导致了他的博士后工作，其中涉及 用于改善内皮细胞对血管支架和移植物的捕获和保留的工程方法。 他的博士后工作还涉及组织工程心脏瓣膜项目，以探索生物和生物合成方法。候选人的直接职业目标是通过完成博士后培训并开始在一所主要研究型大学担任终身教职，从指导过渡到独立研究。 这将需要将他目前的项目集中到一个新的研究方向，同时还需要接受额外的培训，以成功地完成当前和未来的项目作为一个独立的研究者。 K99/R 00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，以有意义地改善患者护理并培养下一代科学家，医生和工程师。 获奖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，阿米尔·勒曼博士，医学博士，是马约诊所心血管研究的主席，提供内皮细胞和血管生物学方面的专业知识。 候选人的共同导师是医学博士Gurpreet Sandhu，博士Dan Dragomir-Daescu博士是马约诊所心导管插入术实验室的主席，提供临床器械原型设计和测试方面的专业知识。他是马约诊所的首席工程师，提供工程设计和分析方面的专业知识，他是明尼苏达大学生物医学工程系主任，提供生物医学工程和心血管组织工程方面的专业知识。 与他的导师合作，候选人将接受临床设备原型设计，新型血管移植物的猪模型分析，新型心脏瓣膜的绵羊模型分析，先进的磁性纳米颗粒合成和先进的静电纺丝技术的培训。 候选人还将接受其他基本技能的培训，包括负责任的研究行为，研究成果的传播，指导和项目管理。 最后，教育机会，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研讨会系列的研究生课程将完成培训经验。 马约诊所通过研究生院、医学院、研究教育办公室和临床和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。 马约诊所致力于支持转化研究，最近成立了再生医学中心作为战略举措。 世界各地的专家在各个领域都可以与改善病人护理的共同目标进行合作。 马约还提供各种研究资源和设施，包括核心设施，如显微镜和细胞分析核心，生物统计学核心，组织学核心，材料和结构测试核心。 工程部设有一个完整的机械车间，电气车间和玻璃吹制车间，以支持工程设计和开发的研究要求。 马约还拥有几个动物设施，包括心血管创新实验室，该实验室设有一个专门用于动物研究的完整的心导管实验室。 拟议的研究项目是候选人正在进行的工作的自然延伸，将其研究集中在一个新的方向，以开始向独立过渡。 所提出的工作解决了通过推进磁内皮化方法来改善植入式心血管装置的血液相容性的重要临床需求。 本研究将利用静电纺丝技术制备具有磁性的生物材料，以开发下一代磁性移植物。 将在体外测试移植物的机械、磁性和促凝性。 然后在猪植入模型中测试移植物的临床相关结局，包括通畅性、血栓形成和新生内膜增生。 这些移植物有望成为临床转化发展的重要一步。 拟议的工作还将开发一种新型的磁功能化和对齐的生物材料，该材料针对机械和磁性进行了优化。 这种生物材料有望在细胞、药物和蛋白质的靶向递送方面具有广泛的重要应用。 拟议的工作将使用一种新的生物材料来制造能够磁性内皮化的新型心脏瓣膜。 将对瓣膜进行体外机械、磁性和血栓形成性能试验。 然后在绵羊植入模型中测试瓣膜的临床相关结局，包括功能、血栓形成和钙化。 预期这些瓣膜将证明瓣膜磁性内皮化的概念验证。