Nanotechnology in tissue engineering for autologous cardiac valve development

用于自体心脏瓣膜发育的组织工程纳米技术

基本信息

批准号：
10227992
负责人：
Soumen Jana
金额：
$ 24.83万
依托单位：
UNIVERSITY OF MISSOURI-COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-10 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10227992
关键词：
Animal Model Animals Anticoagulation Aorta Area Autologous Award Biocompatible Materials Biological Biology Biomedical Engineering Bioprosthesis device Biostatistics Core Cardiac Catheterization Procedures Cardiology Cardiovascular Diseases Cardiovascular Physiology Cardiovascular Surgical Procedures Cardiovascular system Cell Adhesion Cells Cellular biology Clinic Clinical Collaborations Collagen Fibril Communication Research Complex Core Facility Department chair Deposition Development Doctor of Medicine Doctor of Philosophy Elastin Electrospinning Endothelium Engineering Extracellular Matrix Extramural Activities FDA approved Faculty Family suidae Funding Future Goals Heart Valves Heart failure Histology Immune response Implant In Vitro Inflammatory Response Intervention Laboratories Mechanics Medicine Mentors Microscopy Minnesota Modeling Molds Molecular Morphology Nanotechnology Natural regeneration Nature Operative Surgical Procedures Outcome Pathology Patient Care Patient Education Patients Performance Physicians Polymers Positioning Attribute Postdoctoral Fellow Property Prosthesis Radial Regenerative Medicine Regenerative response Research Research Personnel Research Support Resources Schools Science Scientist Series Services Sheep Stents Structure System Technology Testing Thick Thrombus Tissue Engineering Tissues Training Translational Research Tubular formation Universities Washington Work adverse outcome animal facility base biomaterial development calcification cardiac tissue engineering career career development clinical center clinical translation clinically relevant college design education research engineering design experience heart valve replacement implantation improved improved outcome in vitro Model in vitro testing in vivo innovation interstitial materials science mechanical properties nanofiber next generation novel novel strategies patient population pericardial sac polycaprolactone post-doctoral training pressure professor prototype research facility scaffold sheep model skills subcutaneous tenure track translational research program

项目摘要

Project Summary/Abstract The goals of the proposed research are to develop functional autologous trilayered heart valve leaflets with collagen fibril orientations of a native leaflet using trilayered nanofibrous substrates and to extend this approach in developing fully autologous heart valves with native heart valve functionality. The proposed work will develop a technology to fabricate trilayered nanofibrous substrates from a FDA approved polymer mimicking trilayered structure and orientations of collagen fibrils of native heart valve leaflets. The proposed work will then apply leaflet-shaped trilayered nanofibrous substrates to develop non-contractile autologous valve leaflets mimicking the structure of native leaflets by in-body tissue engineering. The leaflet constructs will be tested in-vitro to verify their morphological, structural, and functional properties and contractility. The proposed work will then develop heart valve-shaped nanofibrous substrates containing leaflet-shaped trilayered nanofibrous substrates and circumferentially oriented tubular nanofibrous substrates to engineer autologous non-contractile heart valves with comparable properties of native heart valves through in-body tissue engineering. The engineered valves will be tested for their morphological, structural, mechanical and functional properties in-vitro. The engineered autologous valves will also be tested for clinically-relevant outcomes including function, thrombus formation, and calcification in an ovine implantation model. These valves are expected to be an important step in the development toward clinical translation. The proposed research focuses the candidate's research in a novel direction to provide training on new skills required to begin the transition to independence. The candidate holds a Ph.D. in Materials Science and Engineering from the University of Washington and is currently a research associate at Mayo Clinic. His Ph.D. thesis work involved development of biomaterials for tissue engineering and regenerative medicine. This led to his postdoctoral work that involves design and development of nanofibrous biomaterials for biological cardiac valve development. His postdoctoral work also includes development of decellularized heart valve, pericardium tissue-based heart valve and stent graft, and their functionality testing in an ovine/porcine implantation model. 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 needed to successfully complete the current and future projects in cardiovascular tissue engineering as an independent investigator. The K99/R00 mechanism is the ideal means of achieving this goal. The candidate's long-term career objective is to establish an independent and extramurally funded translational research program within the field of cardiovascular tissue engineering that will 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 cardiovascular biology and clinical are Dr. Leigh Griffith, Ph.D., who is a professor of cardiovascular diseases at Mayo Clinic and provides expertise in biomaterials and in-vivo recipient inflammatory, immune and regenerative responses in cardiovascular area, Dr. John Stulak, M.D., is a professor of cardiovascular surgery at Mayo Clinic and provides expertise in surgical treatment of advanced heart failure, cardiology. The candidate's co-mentors and Dr. Robert Tranquillo, Ph.D., chair of the Department of Biomedical Engineering at the University of Minnesota, provides expertise in biomedical engineering and cardiovascular tissue engineering. Working with his mentors, the candidate will train in scaffold and mold design, cardiovascular physiology, cell biology and pathology, all aspects of in-body tissue engineering in ovine model, functionality tests of tissue-engineered valves and ovine model analysis of novel cardiac valves. The candidate will also train in other essential skills including communication of research findings, mentoring, and project management. Finally, educational opportunities such graduate coursework in molecular cell biology , cardiovascular physiology 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 the common goal to improve patient care. Mayo also offers a variety of research resources and facilities including core facilities such as the Microscopy and Cell Analysis Core, the Biostatistics Core, the Histology Core, and the Materials and Structural Testing Core. The Division of Engineering features a full machine shop, electrical shop, and glassblowing 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 to animal studies.

项目概要/摘要拟议研究的目标是开发功能性自体三层心脏瓣膜小叶使用三层纳米纤维基材的天然小叶的胶原纤维方向并扩展该方向开发具有天然心脏瓣膜功能的完全自体心脏瓣膜的方法。拟议的工作将开发一种技术，用 FDA 批准的聚合物制造三层纳米纤维基材模仿天然心脏瓣膜小叶胶原纤维的三层结构和方向。拟议的然后，工作将应用小叶状三层纳米纤维基材来开发非收缩性自体通过体内组织工程模仿天然小叶的结构的瓣膜小叶。传单结构将进行体外测试，以验证其形态、结构和功能特性以及收缩性。这然后，拟议的工作将开发含有小叶状纳米纤维的心脏瓣膜形状的纳米纤维基材三层纳米纤维基材和周向定向管状纳米纤维基材进行工程设计自体非收缩性心脏瓣膜在体内具有与天然心脏瓣膜相当的特性组织工程。工程阀门将对其形态、结构、机械和性能进行测试体外功能特性。工程自体瓣膜还将接受临床相关测试结果包括绵羊着床模型中的功能、血栓形成和钙化。这些瓣膜有望成为临床转化发展的重要一步。拟议的研究将候选人的研究集中在一个新的方向，以提供新的培训开始向独立过渡所需的技能。候选人拥有博士学位。在材料科学和华盛顿大学工程学博士，目前是梅奥诊所的研究员。他的博士学位。论文工作涉及组织工程和再生医学生物材料的开发。这导致他的博士后工作涉及生物心脏纳米纤维生物材料的设计和开发阀门开发。他的博士后工作还包括脱细胞心脏瓣膜、心包的开发基于组织的心脏瓣膜和支架移植物，及其在羊/猪植入模型中的功能测试。候选人的近期职业目标是从指导过渡到独立研究完成博士后培训并开始在一项重大研究中担任终身教职大学。这需要将他当前的项目集中到一个新颖的研究方向，同时也接受成功完成当前和未来的心血管组织项目需要额外的培训作为一名独立调查员进行工程设计。 K99/R00 机构是实现这一目标的理想方法目标。候选人的长期职业目标是建立一个独立的、外部资助的机构心血管组织工程领域的转化研究计划将有意义改善患者护理并培训下一代科学家、医生和工程师。获奖期间的研究职业发展将包括与跨学科指导团队合作临床医生、科学家和工程师。候选人的主要导师，医学博士阿米尔·勒曼 (Amir Lerman) 博士是梅奥诊所的心血管研究并提供心血管生物学和临床方面的专业知识 Leigh Griffith 博士是心血管学教授梅奥诊所致力于研究疾病，并提供生物材料和体内受体炎症、免疫和心血管领域的再生反应，约翰·斯图拉克博士，医学博士，心血管外科教授在梅奥诊所，提供晚期心力衰竭手术治疗的专业知识，心脏病学。候选人的共同导师和罗伯特博士明尼苏达大学生物医学工程系主任 Tranquillo 博士提供生物医学工程和心血管组织工程方面的专业知识。与他的导师一起工作，候选人将接受培训支架和模具设计、心血管生理学、细胞生物学和病理学等绵羊模型体内组织工程方面、组织工程瓣膜和绵羊的功能测试新型心脏瓣膜的模型分析。候选人还将接受其他基本技能的培训，包括研究成果的交流、指导和项目管理。最后，教育机会这样的研究生课程分子细胞生物学、心血管生理学以及各种研究和临床研讨会系列，将完善培训经验。梅奥诊所提供各种教育和通过研究生院、医学院、研究教育办公室和中心提供支持服务临床和转化科学，这将促进必要的培训。梅奥诊所致力于支持转化研究，最近成立了该中心再生医学作为一项战略举措。各个领域的世界专家都可以为您服务为了改善患者护理的共同目标而进行合作。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。工程系拥有完整的机械车间、电气车间和玻璃吹制车间，以支持工程设计和发展。梅奥还拥有多个动物设施，包括心血管创新实验室、其中设有专门用于动物研究的完整心导管实验室。