Engineering aspects of liver support systems

描述(申请人提供)：尽管肝脏移植手术取得了许多进展，但越来越多的晚期肝脏患者 在等待移植期间，疾病正在死亡。因此，在以下方面取得了进一步进展 供体肝脏的储存以及替代替代方案和 在等待捐赠者肝脏时支持肝功能的机制是 需要的。一个非常有前途的研究和开发领域正在开发中 解决肝脏支持问题的工程解决方案 捐献器官或生物人工肝脏。然而，在一个 单一学科受制于工程和工程的复杂性 这类项目的生物学方面。这项提议构成了一种伙伴关系 生物工程师、生物学家和肝脏移植外科医生之间的合作 结合他们的专业知识来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，例如生物人工肝。该方法 涉及修改支承矩阵以便于提高质量 运输。第二个项目解决了改进后的假设 生物人工肝的功能可以通过提供更具生理性的 支撑装置中的单元类型的组合。具体来说，我们将 Kupffer细胞与肝细胞关系的研究 在培养中维持长时间的肝脏特异性功能。期末专题 重点发展优化微血管血流灌注的方法 在机器灌流的肝脏中。这个项目使用了Intra Variable的组合 显微镜和数学建模。在所有项目中，工程和 生物学方法和临床经验相结合，以解决 聚焦、临床相关的问题。此外，独特的环境， 支持合作伙伴关系将最大限度地提高在这方面的成功潜力 跨学科的方法，为潜在的临床提供了一条途径 实验室先进技术的应用。

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.