Development of Second Generation Tissue Engineered Vascular Grafts

描述（由申请人提供）： 该提案描述了一个为期5年的培训计划，以发展外科学术生涯。主要研究者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。该计划将进一步发展组织工程技术用于治疗心血管疾病的主要研究者指挥。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。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。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计划的主任，并培养了许多博士后研究员，包括一些外科医生科学家。此外，一个由德高望重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。在这个建议中，我们将探讨应用药物输送和基因工程原理设计的组织工程血管导管，试图抑制形成的新生内膜增生，血管移植失败的主要原因。具体目标包括：1）建立了一种研究组织工程血管移植物中新生内膜增生的体内模型，2）确定西罗莫司的控释是否（雷帕霉素）可以抑制新生内膜增生的发展，和3）确定是否过度表达内皮型一氧化氮合酶（eNOS），通过细胞构建的组织工程化血管导管可以抑制新生内膜增生的形成。耶鲁大学通过将来自不同资源的专业知识融入定制课程，为培训医生科学家提供了理想的环境。这样的环境最大限度地发挥了主要研究者的潜力，以建立一个科学的利基，从学术生涯可以构建。

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.