Engineering aspects of liver support systems

肝脏支持系统的工程方面

• 批准号: 6524322
• 负责人: MARK G CLEMENS
• 金额: $ 41.13万
• 依托单位: UNIVERSITY OF NORTH CAROLINA CHARLOTTE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6524322
• 关键词: bioengineering /biomedical engineering; biomaterial development /preparation; biomaterial interface interaction; cell cell interaction; cell population study; enzyme linked immunosorbent assay; gelatin; human subject; immunocytochemistry; intravital microscopy; laboratory rat; liver cells; liver disorder; liver preservation; liver regeneration; liver transplantation; mathematical model; medical complication; model design /development; morphometry; oxygen transport; respiratory oxygenation; terminal nick end labeling; tissue engineering; tissue support frame

DESCRIPTION (provided by applicant): In spite of many advances in liver transplant surgery, an increasing number of patients with terminal liver disease are dying while awaiting transplants. Consequently, further advances in the storage of donor livers, as well as alternative replacement options and mechanisms for supporting liver function while awaiting a donor liver are needed. A very promising area of research and development is in the development of engineered solutions to the problems of liver support for either natural donor organs or bioartificial livers. However, efforts undertaken within a single discipline are hampered by the complexity of both the engineering and biological aspects of such projects. This proposal constitutes a partnership between bioengineers, biologists and a liver transplant surgeon with the goal of combining their expertise to devise improved methods of liver support via bioartificial livers and improved preservation of donor livers via machine perfusion preservation (MPP). The partnership encompasses three inter-related projects. The first project focuses on delivery of oxygen and other nutrients to the cells in in vitro systems such as the bioartificial liver. The approach involves the modification of the support matrix to facilitate enhanced mass transport. The second project addresses the hypothesis that improved bioartificial liver function can be attained by providing a more physiological combination of cell types in the support device. Specifically, we will investigate the relationship between Kupffer cells and hepatocytes in maintaining prolonged hepatic-specific function in culture. The final project focuses on development of methods for optimization of microvascular perfusion in machine-perfused livers. This project uses a combination of intravital microscopy and mathematical modeling. In all of the projects, engineering and biological approaches, as well as clinical experience, are combined to address focused, clinically relevant problems. Moreover, the unique environment that supports the partnership will maximize the potential for success in this interdisciplinary approach and provide an avenue for potential clinical application of laboratory advances.

描述（由申请人提供）：尽管肝移植手术取得了许多进展，但越来越多的晚期肝脏患者