VASCULAR TISSUE ENGINEERING: RATIONAL DESIGN USING MODELING

血管组织工程：利用建模进行合理设计

• 批准号: 8357833
• 负责人: Stephen F Hanson
• 金额: $ 5.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357833
• 关键词: Animal Model; Beds; Biochemical; Biological Assay; Blood; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cell surface; Collagen; Elastin; Endothelial Cells; Funding; Goals; Grant; Healed; Hemostatic Agents; Hemostatic function; Histologic; Hyperplasia; In Vitro; Inflammatory; Modeling; Molecular; National Center for Research Resources; Operative Surgical Procedures; Outcome; Papio; Physiological; Primates; Principal Investigator; Property; Proteins; Research; Research Infrastructure; Resources; Source; Stem cells; Testing; Thrombosis; Thrombus; Tissue Engineering; United States National Institutes of Health; Vascular Graft; Whole Blood; cell type; cost; design; healing; hemodynamics; improved; in vivo; preconditioning; response; vascular tissue engineering

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Tissue engineering holds promise for the treatment of cardiovascular disease. For tissue-engineered cardiovascular constructs a nonthrombogenic endothelial cell (EC) surface will be advantageous. Our goal is to establish, for blood-contacting EC surfaces, relationships between pro- and anti- hemostatic properties of ECs that can be preconditioned in vitro, and physiologic responses of thrombosis and vascular healing in vivo. To achieve this goal, the hemostatic properties of constructs variably preconditioned in vitro are being correlated with in vivo outcomes, thereby documenting the utility of rational design. These studies employ baboon endothelial progenitor cells (EPCs) that are readily isolated from whole blood in vitro, and relevant in vivo baboon models of thrombosis and vascular graft intimal hyperplasia. To enhance or inhibit EPC properties that regulate hemostatic functions, EPCs are grown on conventional ePTFE coated with different matrix proteins (collagen or elastin) and subjected to variable hemodynamic preconditioning (static vs. normal shear). Hemostatic, inflammatory, and mitogenic activities that are orchestrated by EPCs are assessed using functional, biochemical, molecular, and histologic assays. We are assessing: 1) thrombus formation in native, non-anticoagulated blood under physiologic flow conditions, and 2) healing of EPC-constructs following surgical placement. It is not our goal to develop an improved vascular graft. Rather, by documenting that cellular preconditioning in vitro can predictably improve outcomes in vivo - a principle that can be extended to other cell types and animal models - these results will validate rational design in general, and encourage studies with other constructs and test beds.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 组织工程学为心血管疾病的治疗带来了希望。对于组织工程化的心血管结构，非血栓形成内皮细胞（EC）表面将是有利的。我们的目标是建立，对于血液接触EC表面，可以在体外预处理的EC的促止血和抗止血性质与体内血栓形成和血管愈合的生理反应之间的关系。为了实现这一目标，将体外预处理的结构的止血特性与体内结果相关联，从而记录合理设计的实用性。这些研究采用狒狒内皮祖细胞（EPC），很容易从全血中分离的体外，和相关的体内狒狒模型血栓形成和血管移植内膜增生。为了增强或抑制调节止血功能的EPC特性，EPC在涂覆有不同基质蛋白（胶原蛋白或弹性蛋白）的常规ePTFE上生长，并经受可变的血液动力学预处理（静态与正常剪切）。通过功能、生化、分子和组织学检测评估由EPCs协调的止血、炎症和促有丝分裂活性。我们正在评估：1）在生理流动条件下，自体非抗凝血液中的血栓形成，以及2）手术放置后EPC结构的愈合。我们的目标不是开发一种改进的血管移植物。相反，通过证明体外细胞预处理可以可预测地改善体内结果-这一原理可以扩展到其他细胞类型和动物模型-这些结果将验证一般的合理设计，并鼓励使用其他构建体和试验床进行研究。