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比例（在美国是导致死亡的主要原因，影响了1200万美国人），每年给社会造成的损失超过1100亿美元。由于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导管，因此临床上对小直径血管的移植有很大的需求。组织工程显然有可能在这方面提供缓解，然而，由于实用性和可行性问题或涉及外来材料，目前的尝试具有有限的临床潜力。因此，提出了一种新的组织组装方法来避免这些缺陷。新方法