Convective Flow Tissue Assembly of Vascular Grafts

冠心病占心脏病的最大比例(在美国是主要的死亡原因，影响了1200万美国人)，每年给社会造成的损失超过1100亿美元。临床上对小直径血管移植物的需求很大，因为需要多次或重复搭桥手术的患者往往缺乏足够的自体血管作为搭桥管道。组织工程显然具有缓解这一领域的潜力，然而，由于实用性和可行性问题或涉及到外来材料，目前的尝试具有有限的临床潜力。因此，提出了一种避免这些缺陷的新的组织组装方法。新方法论 依靠阻力诱导的对流在惰性多孔芯棒上组装组织，该芯棒后来被移除，产生完全生物结构。血流将由跨壁压力梯度产生，这反过来将产生模拟天然动脉机械环境的剪应力。组织组装方法将允许多个苗种，从而使分层组织的培养成为可能，并将容易放大和自动化，从而允许广泛的商业和临床应用。目前的第一阶段提案旨在测试新型生物反应器设计将人类平滑肌细胞组装成厚的、健康的三维组织结构的能力。这些 构造将根据物理和形态特性进行评估。最终目标是开发一种组织组装方法，该方法通过易于以经济的方式放大的制造方法来生产具有一致的生物和机械性能的自体和完全生物的血管移植物。

Coronary heart disease accounts for the largest fraction of heart disease (the leading cause of death in the United States, affecting 12 million Americans) and has an annual cost to society that exceeds 110 billion dollars. There is a great clinical need for small diameter vascular artery grafts, as patients requiring multiple or repeat bypass procedures frequently lack adequate autogenous vessels to serve as bypass conduit. Tissue engineering clearly has the potential to provide relief in this area, however, present attempts have had limited clinical potential, due to practicality and feasibility issues or involvement of foreign materials. As such, a novel tissue assembly methodology that avoids these pitfalls is proposed. The new methodology relies upon drag-induced convective flow to assemble tissue on an inert porous mandrel, which is later removed, yielding completely biological constructs. The flow will be generated by a transmural pressure gradient, which in turn will generate shear stresses that will mimic the mechanical environment of native arteries. The tissue assembly methodology will allow for multiple seedings, such that the culture of layered tissues is possible, and will be readily scaled up and automated, allowing for wide-scale commercial and clinical application. The present Phase I proposal seeks to test the ability of the novel bioreactor design to assemble human smooth muscle cells into thick, healthy three-dimensional tissue constructs. These constructs will be evaluated in terms of physical and morphological properties. The ultimate goal is to develop a tissue assembly method that produces autologous and completely biological vascular grafts, which are produced with consistent biological and mechanical properties, by a manufacturing process that can be readily scaled-up in an economic manner.