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:
    9381682
  • 负责人:
  • 金额:
    $ 12.81万
  • 依托单位:
  • 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 2019-06-30
  • 项目状态:
    已结题

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.
项目总结/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底的天然小叶的胶原原纤维取向, 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 模拟天然心脏瓣膜小叶的胶原纤维的三层结构和取向。拟议 然后,工作将应用小叶状三层纳米纤维基质来开发非收缩性自体 通过体内组织工程模拟天然小叶结构的瓣膜小叶。瓣叶结构将 在体外进行测试,以验证其形态、结构和功能特性以及收缩性。的 然后,拟议的工作将开发心脏瓣膜形纳米纤维基质, 三层纳米纤维基材和周向取向的管状纳米纤维基材 具有与自体心脏瓣膜相当的特性的自体非收缩性心脏瓣膜通过体内 组织工程学将对工程瓣膜的形态、结构、机械和 体外功能特性。还将对工程自体瓣膜进行临床相关试验, 结果包括绵羊植入模型中的功能、血栓形成和钙化。这些 瓣膜有望成为向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。材料科学与 工程从华盛顿大学,目前是一个研究助理在马约诊所。博士学位 论文工作涉及组织工程和再生医学的生物材料开发。这导致 他的博士后工作涉及设计和开发用于生物心脏的纳米纤维生物材料 瓣膜发育他的博士后工作还包括开发脱细胞心脏瓣膜,心包 基于组织的心脏瓣膜和覆膜支架,及其在绵羊/猪植入模型中的功能试验。 候选人的直接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,同时还需要获得 成功完成当前和未来心血管组织项目所需的额外培训 工程师作为独立调查员。K99/R 00机制是实现这一目标的理想手段 目标.候选人的长期职业目标是建立一个独立的和校外资助的 心血管组织工程领域的转化研究计划,将有意义 改善病人护理,培养下一代科学家、医生和工程师。 在奖励期间的研究职业发展将包括与跨学科的指导团队合作 临床医生、科学家和工程师。候选人的主要导师,阿米尔·勒曼博士,医学博士,是 马约诊所的心血管研究,提供心血管生物学和临床方面的专业知识 是利·格里菲斯博士他是一位心血管教授, 马约诊所的疾病,并提供生物材料和体内受体炎症,免疫和 再生反应在心血管领域,博士约翰Stulak,医学博士,是一位心血管外科教授 在马约诊所,并提供先进的心脏衰竭手术治疗的专业知识, 心脏病学候选人的共同导师 罗伯特博士 Tranquillo博士,明尼苏达大学生物医学工程系主任, 在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,所有 绵羊模型体内组织工程方面,组织工程瓣膜和绵羊的功能试验 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 这种研究生课程, 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。马约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 临床和翻译科学,这将有助于必要的培训。 马约诊所致力于支持转化研究,最近成立了 再生医学作为一项战略举措。世界各地的专家在各个领域都可以为 共同的目标,以改善病人的护理。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,生物统计核心, 组织学核心以及材料和结构测试核心。工程部的特点是一个完整的 机械车间、电气车间和玻璃吹制车间,以支持工程设计和 发展马约还有几个动物设施,包括心血管创新实验室, 该中心设有一个专门用于动物研究的完整的心导管实验室。

项目成果

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Soumen Jana其他文献

Soumen Jana的其他文献

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{{ truncateString('Soumen Jana', 18)}}的其他基金

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
  • 批准号:
    10227992
  • 财政年份:
    2017
  • 资助金额:
    $ 12.81万
  • 项目类别:

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