Convective Flow Tissue Assembly of Vascular Grafts

血管移植物的对流组织组装

• 批准号: 6789048
• 负责人: JOHN A FRANGOS
• 金额: $ 19.13万
• 依托单位: APPLIED TISSUE AND MATERIALS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2005-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6789048
• 关键词: biomechanics; biotechnology; blood vessel transplantation; cell adhesion molecules; cell differentiation; coronary artery; coronary bypass; histology; myosins; shear stress; stainings; technology /technique development; tissue /cell culture; tissue engineering; vascular smooth muscle

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.

冠心病占心脏病的最大部分（在美国是死亡的主要原因，影响1200万美国人），并且每年对社会的成本超过1100亿美元。临床上非常需要小直径血管动脉移植物，因为需要多次或重复旁路手术的患者通常缺乏足够的自体血管作为旁路管道。组织工程显然具有在该领域提供缓解的潜力，然而，由于实用性和可行性问题或异物的参与，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陷阱的新型组织组装方法。新方法 依靠阻力诱导的对流将组织组装在惰性多孔芯轴上，随后将其移除，从而产生完全的生物结构。通过跨壁压力梯度产生血流，进而产生剪切应力，模拟自体动脉的机械环境。该组织组装方法将允许多次分离，使得分层组织的培养是可能的，并且将容易地按比例放大和自动化，从而允许大规模商业和临床应用。目前的I期提案旨在测试新型生物反应器设计将人平滑肌细胞组装成厚的健康三维组织结构的能力。这些 将根据物理和形态学性质评价构建体。最终目标是开发一种组织组装方法，该方法通过可以以经济的方式容易地按比例放大的制造工艺来生产具有一致的生物和机械特性的自体和完全生物的血管移植物。