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Use of Perfluorocarbons to Enhance the Performance of Perfused Three-Dimensional Hepatic Cultures

机译:使用全氟化碳来增强灌注三维肝培养物的性能

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摘要

Bioartificial liver devices (BALs) are extracorporeal systems designed to temporarily bridge patients until a suitable donated liver is available for transplantation and also have value for pharmaceutical testing applications. Yet critical issues exist that limit the functional performance of their current designs. One of these concerns scale up issues connected to oxygen (O2) delivery to the cells housed within their three-dimensional (3D) configurations, and its consequences to device performance. As primary blood substitute candidates with extraordinarily high O2 capacity, perfluorocarbons (PFCs) offer hope as one strategy for addressing the O2 delivery issue encountered when scaling up the tissue space of current BAL designs. This study utilizes a PFC-based second-generation O2 carrier OXYCYTE?, as an additive to regular nutrient medium, for augmenting O2 delivery in a customized 3D tissue assembly system. The results demonstrate that the addition of PFCs significantly increases the O2 capacity of regular medium and that net cytochrome P450 activity levels are considerably increased under flow in PFC-treated systems, as compared to controls. This work thus clarifies the benefits of using PFCs to enhance the functional performance of 3D liver systems.
机译:生物人工肝装置(BAL)是一种体外系统,旨在临时桥接患者,直到有合适的捐赠肝脏可供移植为止,并且对于药物测试应用也具有价值。但是仍然存在一些关键问题,这些问题限制了其当前设计的功能性能。这些问题之一是扩大与将氧气(O2)输送到其三维(3D)配置内的电池有关的问题及其对设备性能的影响。作为具有超高O2容量的主要血液替代候选物,全氟化碳(PFC)作为解决当前BAL设计扩大组织空间时遇到的O2输送问题的一种策略提供了希望。这项研究利用了基于PFC的第二代O2载体OXYCYTE™作为常规营养培养基的添加剂,以增加在定制3D组织组装系统中的O2传递。结果表明,与对照相比,在PFC处理的系统中,PFC的添加显着增加了常规培养基的O2容量,并且在流动条件下,细胞色素P450的净净活性水平显着提高。因此,这项工作阐明了使用PFC增强3D肝脏系统功能的好处。

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