TISSUE ENGINEERING OF BLOOD VESSEL SUBSTITUTES

描述 (改编自申请人的摘要)心血管疾病继续 是这个国家发病率和死亡率的主要原因。疾病 牵涉到弹性动脉和肌肉动脉的突起构成了狮子的 从冠状动脉疾病到各种不同的病理 颈动脉狭窄。应用最广泛的外科手术治疗 受影响的血管结构是公开进行的“搭桥术”，通常 采用自体静脉重建血管&5 mm及假体 适用于较大的弹性容器的设备。自体静脉和永久性静脉 假肢装置在这些方面有许多固有的局限性 应用，如感染和血栓形成。一种组织工程血液 由合成的可生物降解的聚合物支架构建的容器管道 已植入自体的合适的细胞类型可能代表 具有可衡量优势的新一代血管移植物。申请者 计划建造大口径和小口径的血管管道 体循环重建通过一系列确定的 步骤：(1)建立最佳的细胞收获和培养条件 三类细胞贴壁/增殖谱分析 聚合物，(2)构建组装的最佳方法的确定和 利用动态组织培养生物反应器进行组织培养及(3) 发展小型和大型动物模型以允许在体内进行严格的实验 组织工程血管与现有血管的比较 外科技术。最后，申请者将与他们的 合作者对Smooth进行特定的细胞和分子分析 以及天然血管和工程血管中的内皮细胞。而当 初步研究令人鼓舞，关于细胞的信息 组织工程导管的生物学研究很少。

DESCRIPTION (Adapted from the applicant's abstract) Cardiovascular disease continues to be the leading cause of morbidity and mortality in this country. Disease processes involving the elastic and muscular arteries constitute the lion's share of this, with diverse pathology ranging from coronary artery disease to carotid stenosis. The most widely applied surgical intervention for affected vascular structures is openly-performed "bypass" which generally employs autogenous vein for reconstruction of vessels <5 mm and prosthetic devices for larger, elastic vessels. Autogenous veins and permanent prosthetic devices have a number of intrinsic limitations for these applications, such as infection and thrombosis. A tissue engineered blood vessel conduit constructed from a synthetic biodegradable polymer scaffold that has been seeded with autologous, appropriate cell types may represent a new generation of vascular graft with measurable advantages. The applicants plan to construct large and small calibers of blood vessel conduits for reconstruction in the systemic circulation through a defined series of steps: (1) establishment of optimal cell harvest and culture conditions and analysis of the cell attachment/proliferation profiles of three categories of polymers, (2) determination of optimal methods of construct assembly and in vitro tissue cultivation using dynamic tissue culture bioreactors and (3) development of small and large animal models to permit rigorous in vivo comparison of tissue engineered blood vessels with currently available surgical technologies. Finally, the applicants will work closely with their collaborators to carry out specific cell and molecular analyses of smooth and endothelial cells in native and engineered blood vessels. While the preliminary studies have been encouraging, information concerning the cell biology of tissue engineered conduits is scant.