Development of Second Generation Tissue Engineered Vascular Grafts

第二代组织工程血管移植物的开发

• 批准号: 7075192
• 负责人: christopher Kane breuer
• 金额: $ 13.31万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7075192
• 关键词: SCID mouse; cardiovascular disorder therapy; chemoprevention; clinical research; computed axial tomography; disease /disorder model; enzyme activity; gene expression; graft versus host disease; heart /lung bypass; human subject; hyperplasia; magnetic resonance imaging; model design /development; nitric oxide synthase; pharmacokinetics; sirolimus; therapy design /development; tissue engineering; transplant rejection; vascular endothelium

DESCRIPTION (provided by applicant): This proposal describes a 5-year training program for the development of an academic career in surgery. The principal investigator has completed surgical training at Brown University and a research fellowship in tissue engineering at Harvard University and now, will expand upon his scientific skills through a unique integration of interdepartmental resources. This program will further develop the principal investigators command of tissue engineering techniques for the treatment of cardiovascular diseases. W. Mark Saltzman will mentor the principal investigator's scientific development. Dr. Saltzman is a recognized leader in the field of tissue engineering. He is chairman of the Department of Biomedical Engineering and has trained numerous postdoctoral fellows and graduate students. Jordan S. Pober will co-mentor the principal investigator's scientific development. Dr. Pober is a recognized leader in the field of vascular biology. He is director of the Interdepartmental Vascular Biology and Transplantation Program and has trained many postdoctoral fellows including a number of surgeon-scientists. In addition, an advisory committee of highly regarded medical scientists will provide scientific and career advice. Research will focus on development of tissue engineered vascular conduits for use in bypass surgery. In this proposal we will explore the application of both drug delivery and genetic engineering principles to the design of tissue engineered vascular conduits in an attempt to inhibit the formation of neointimal hyperplasia, a leading cause of vascular graft failure. Specific aims include: 1) Establishing a model for investigating the development of neointimal hyperplasia in tissue engineered vascular grafts in vivo, 2) Determining if controlled release of sirolimus (rapamycin) from the scaffold used to construct tissue engineered vascular conduits can inhibit the development of neointimal hyperplasia, and 3) Determining if overexpression of endothelial nitric oxide synthase (eNOS) by the cells used to create tissue engineered vascular conduits can inhibit the formation of neointimal hyperplasia. Yale University provides an ideal setting for training physician scientists by incorporating expertise from diverse resources into customized programs. Such an environment maximizes the potential for the principal investigator to establish a scientific niche from which an academic career can be constructed.

描述（由申请人提供）： 该提案描述了一个为期 5 年的外科学术职业发展培训计划。首席研究员已在布朗大学完成了外科培训，并在哈佛大学获得了组织工程研究奖学金，现在将通过独特的跨部门资源整合来扩展他的科学技能。该计划将进一步培养主要研究人员对治疗心血管疾病的组织工程技术的掌握。 W. Mark Saltzman 将指导首席研究员的科学发展。 Saltzman 博士是组织工程领域公认的领导者。现任生物医学工程系系主任，培养了多名博士后和研究生。 Jordan S. Pober 将共同指导首席研究员的科学发展。 Pober 博士是血管生物学领域公认的领导者。他是跨部门血管生物学和移植项目的主任，并培养了许多博士后研究员，其中包括一些外科医生科学家。此外，由备受尊敬的医学科学家组成的咨询委员会将提供科学和职业建议。研究将集中于开发用于搭桥手术的组织工程血管导管。在本提案中，我们将探索药物输送和基因工程原理在组织工程血管导管设计中的应用，试图抑制新生内膜增生的形成，新生内膜增生是血管移植失败的主要原因。具体目标包括：1) 建立一个模型，用于研究体内组织工程血管移植物中新内膜增生的发展，2) 确定从用于构建组织工程血管导管的支架中控制释放西罗莫司（雷帕霉素）是否可以抑制内膜增生的发展。新生内膜增生，以及 3) 确定用于创建组织工程血管导管的细胞过度表达内皮一氧化氮合酶 (eNOS) 是否可以抑制内膜增生的形成新内膜增生。耶鲁大学通过将不同资源的专业知识融入定制项目，为培训医师科学家提供了理想的环境。这样的环境最大限度地发挥了首席研究员建立科学利基的潜力，并以此为基础构建学术生涯。