Nanotechnology for magnetic endothelialization of implantable cardiovascular devices

 描述(申请人提供)：项目(摘要/摘要应聘者拥有西北大学生物医学工程博士学位，现为梅奥诊所副研究员。他的研究兴趣是心血管组织工程领域。他的毕业论文工作涉及一种分子生物学方法，用于改善血管移植物上内皮细胞的保留率。这导致了他的博士后工作，其中包括 改善内皮细胞在血管支架和移植物上捕获和保持的工程方法。他的博士后工作还包括一个组织工程心脏瓣膜项目，以探索生物和生物合成方法。这位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，从有指导的研究过渡到独立研究。这将需要将他目前的项目集中在一个新的研究方向上，同时还需要接受作为独立调查员成功完成当前和未来项目所需的额外培训。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、由外部资金资助的研究计划，以便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。获奖期间的研究生涯发展将包括与由临床医生、科学家和工程师组成的跨学科指导团队合作。候选人的主要导师，医学博士阿米尔·勒曼博士是梅奥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：Gurpreet Sandhu博士，医学博士，他是Mayo Clinic心脏插管实验室的主席，提供临床设备原型设计和测试方面的专业知识；Dan Dragomir-Daescu博士，博士，他是Mayo诊所的首席工程师，提供工程设计和分析方面的专业知识；Robert特兰quillo博士，博士，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，候选人将在临床设备原型设计、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电纺技术方面进行培训。应聘者还将接受其他基本技能的培训，包括负责任的研究指导、赠款、研究成果的交流、指导和项目管理。最后，教育机会，如再生医学、心血管生理学、数据分析和统计学的研究生课程，以及各种研究和临床研讨会系列将完善培训经验。梅奥诊所通过研究生院、医学院、研究教育办公室以及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。梅奥诊所致力于支持转化研究，最近成立了再生医学中心，作为一项战略举措。不同领域的世界专家可以为改善患者护理这一共同目标进行合作。梅奥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，生物统计核心，组织学核心，以及材料和结构测试核心。工程部设有全套机械车间、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。梅奥还拥有几个动物设施，包括心血管创新实验室，该实验室拥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，该工作将他的研究集中在一个新的方向上，以开始向独立的过渡。这项拟议的工作解决了通过推进磁性内皮化方法来改善植入的心血管装置的血液相容性的重要临床需求。这项拟议的工作将开发下一代磁性接枝，通过使用静电纺丝制造方法来生成磁性纳米纤维生物材料。这些移植物将在体外进行机械、磁性和血栓形成性能的测试。然后将在猪植入模型中测试移植物的临床相关结果，包括通畅性、血栓形成和新的内膜增生。这些移植物有望成为临床翻译发展的重要一步。这项拟议的工作还将开发一种新型的磁性功能化和取向的纳米纤维生物材料，该材料的机械和磁性都得到了优化。这种生物材料有望在细胞、药物和蛋白质的靶向输送方面有广泛的重要应用。这项拟议的工作将使用一种新的生物材料来制造能够实现磁性内皮化的新型心脏瓣膜。这些瓣膜将在体外进行机械、磁性和血栓形成性能测试。然后将在绵羊植入模型中测试瓣膜的临床相关结果，包括功能、血栓形成和钙化。这些瓣膜有望证明瓣膜磁性内皮化的概念。

 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.