Development of Second Generation Tissue Engineered Vascular Grafts

描述(由申请人提供)： 这份提案描述了一项为期5年的培训计划，旨在发展外科的学术生涯。这位首席研究员已经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，他将通过独特的跨部门资源整合来扩展他的科学技能。这一计划将进一步培养组织工程技术在心血管疾病治疗方面的主要研究人员的能力。W.Mark Saltzman将指导首席研究员的科学发展。萨尔茨曼博士是组织工程领域公认的领导者。他是生物医学工程系主任，培养了许多博士后研究员和研究生。乔丹·S·波伯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，培养了许多博士后研究员，包括一些外科科学家。此外，一个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。研究的重点将是开发用于搭桥手术的组织工程血管管道。在这项提案中，我们将探索将药物输送和基因工程原理应用于组织工程化血管管道的设计，试图抑制新生内膜增生的形成，新生内膜增生是导致血管移植失败的主要原因。具体目的包括：1)建立研究组织工程血管移植物体内新生内膜增生的模型，2)确定从构建组织工程血管管道的支架中控制释放西罗莫司(雷帕霉素)是否可以抑制新的内膜增生的发展，以及3)确定用于构建组织工程血管管道的细胞过度表达内皮型一氧化氮合酶(ENOS)是否可以抑制新的内膜增生的形成。耶鲁大学通过将来自不同资源的专业知识整合到定制项目中，为培训内科科学家提供了理想的环境。这样的环境最大限度地增加了首席研究人员建立一个科学利基的潜力，可以在这个利基上建立学术生涯。

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.