TISSUE ENGINEERING OF BLOOD VESSEL SUBSTITUTES

描述 （改编自申请人摘要）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 涉及弹性和肌肉动脉的过程构成了狮子的 这一份额，与不同的病理，从冠心病， 颈动脉狭窄 应用最广泛的外科干预， 受影响的血管结构是开放性的“旁路”， 采用自体静脉重建小于5 mm的血管， 用于较大的弹性血管的装置。 自体静脉和永久性 假体装置具有许多固有的局限性 应用，例如感染和血栓形成。 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血管导管 已经用自体接种的合适的细胞类型可以代表 新一代血管移植物，具有可衡量的优势。 申请人 计划建造大口径和小口径的血管管道， 通过一系列确定的 步骤：（1）建立最佳细胞收获和培养条件， 分析三种类型的细胞附着/增殖概况 （2）确定构建组装的最佳方法， 使用动态组织培养生物反应器的体外组织培养和（3） 开发小型和大型动物模型，以允许严格的体内 组织工程血管与现有血管的比较 外科技术 最后，申请人将与他们的 合作者进行特定的细胞和分子分析平滑 以及天然和工程血管中的内皮细胞。 而 初步研究令人鼓舞，有关该细胞的信息 组织工程管道的生物学研究还很缺乏。

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.