Engineering aspects of liver support systems

肝脏支持系统的工程方面

• 批准号: 6617830
• 负责人: MARK G CLEMENS
• 金额: $ 42.37万
• 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 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6617830
• 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）：尽管肝脏研究取得了许多进展， 移植手术，越来越多的患者与终端肝 在等待移植的过程中死亡。因此，在以下方面的进一步进展 供体肝脏的储存，以及替代替代方案， 在等待供体肝脏时支持肝功能的机制是 needed.一个非常有前途的研究和发展领域是在发展 针对自然肝脏支持问题的工程解决方案 捐赠器官或生物人工肝脏然而，在一个 单一学科受到工程和 这些项目的生物方面。这一提议构成了一种伙伴关系 在生物工程师、生物学家和肝脏移植外科医生之间， 结合他们的专业知识，通过以下方式设计改进的肝脏支持方法： 生物人工肝和通过机器改进的供体肝脏保存 灌注保存（MPP）。该伙伴关系包括三个相互关联的 项目第一个项目的重点是氧气和其他营养物质的输送 到体外系统中的细胞，如生物人工肝。的方法 包括修改支持矩阵，以促进增强质量 运输第二个项目解决的假设，改善 生物人工肝的功能可以通过提供一个更生理化的 支持装置中的细胞类型的组合。具体来说，我们将 探讨枯否细胞与肝细胞在肝细胞分化中的关系。 在培养物中维持延长的肝特异性功能。最终项目 专注于微血管灌注优化方法的开发 在机器灌注的肝脏中。这个项目使用了一个结合的活体 显微镜和数学建模。在所有的项目中，工程和 结合生物学方法和临床经验， 专注于临床相关的问题此外，独特的环境， 支持伙伴关系将最大限度地发挥成功的潜力， 跨学科方法，并为潜在临床 实验室的进步。