in vivo Evaluation of a Tissue Blood Vessel

描述（由申请人提供）： 冠心病是工业化国家的主要死亡原因。尽管基于导管的干预取得了进展，但旁路仍然是具有最大长期疗效的治疗方法。这种方法的主要局限性是原生血管的可用性。研究人员已经研究了合成移植物、细胞接种合成物和脱细胞组织作为天然移植物的替代品。这些替代血管管道受到早期血栓形成和/或动脉瘤的限制。我们已经开发了一种完全自体的人组织工程血管（TEBV），具有功能性内皮和20倍生理血压的爆破压力。由于血管是完全自体的，我们预计不会发生免疫反应和随后的降解。我们已经完成了我们的第一阶段目标，即自动化制造这些TEBV的关键步骤，并且我们已经对从患有晚期血管疾病的人身上采集的细胞构建的TEBV进行了生物力学表征。我们将这些人血管异种移植到犬和大鼠中（分别为14天和90天通畅率），以成功证明短期机械强度和抗血栓形成性。在第二阶段，我们将： .在动物模型中评估功效，优化人TEBV的顺应性和强度。研究扩散并优化单位厚度的强度 .整合生物反应器模块

DESCRIPTION (provided by applicant): Coronary heart disease is the leading cause of death in the industrialized world. Despite advances in catheter-based interventions, bypass remains the treatment with the greatest long-term efficacy. The primary limitation of this approach is the availability of native vessels. Researchers have investigated synthetic grafts, cell seeded synthetics, and decellularized tissues as alternates to native grafts. These alternative vascular conduits are limited by early thrombosis and/or aneurysm. We have developed a completely autologous human tissue engineered blood vessel (TEBV) with a functional endothelium and burst pressures 20-fold physiological blood pressure. Since the vessel is completely autologous, we do not expect immune reaction and subsequent degradation. We have completed our Phase I objectives of automating key steps in the fabrication of these TEBVs and we have biomechanically characterized TEBVs built from cells harvested from humans with advanced vascular disease. We have xenografted these human vessels into canines and rats (14 and 90 day patency respectively) to successfully demonstrate short-term mechanical strength and anti-thrombogenicity. In Phase II, we will: . Evaluate efficacy in an animal model,Optimize compliance and strength of the human TEBVs, . Study diffusion and optimize strength per unit thickness . Integrate the bioreactor modules