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）：尽管肝移植手术有许多进展，但末端肝脏患者数量越来越多 疾病在等待移植时死亡。因此，进一步的进步 供体肝的存储以及替代替代选项和 在等待供体肝的同时支持肝功能的机制是 需要。发展和发展的一个非常有希望的领域是发展 工程解决方案，用于对任何一种自然的肝脏支持问题 供体器官或生物人工肝。但是，在 单一纪律受到工程和工程的复杂性的阻碍 此类项目的生物学方面。该建议构成合作伙伴关系 在生物工程师，生物学家和肝移植外科医生之间 结合其专业知识以通过 生物人工肝并改善了通过机器保存供体肝 灌注保存（MPP）。该合作伙伴关系包括三个相关的 项目。第一个项目着重于氧气和其他营养素的递送 到体外系统中的细胞，例如生物人工肝脏。方法 涉及对支持矩阵的修改以促进增强的质量 运输。第二个项目解决了改善的假设 可以通过提供更多生理学来实现生物人工肝功能 支持设备中的单元格类型的组合。具体来说，我们会的 研究Kupffer细胞与肝细胞之间的关系 维持较长的肝特异性功能。最终项目 着重于开发微血管灌注的方法 在机器渗透的肝脏中。该项目结合了插入 显微镜和数学建模。在所有项目，工程和 生物学方法以及临床经验都合并为解决 专注于临床相关的问题。而且，独特的环境 支持伙伴关系将最大化成功的潜力 跨学科方法，为潜在临床提供途径 实验室进步的应用。