Optimizing the fluidized bed bioreactor as an external bioartificial liver
Optimizing the fluidized bed bioreactor as an external bioartificial liver
复制标题
DOI：
10.5301/ijao.5000567
复制
发表时间：
2017-04-01
影响因子：
1.7
通讯作者：
Legallais, Cecile
中科院分区：
文献类型：
--
作者：
Figaro, Sarah;Pereira, Ulysse;Legallais, Cecile
背景：我们的团队之前设计并验证了一种名为 Suppliver 的新型生物人工肝 (BAL)，其基于 Prismaflex (TM) 设备，包括容纳藻酸盐封装肝细胞的流化床生物反应器。为了确保生物反应器内的正确流化，珠子需要通过添加惰性玻璃微球而变得更重。方法：在本研究中，我们评估了这种附加成分对珠子生产过程、床流化、传质和珠子机械性能以及细胞活力和基本代谢功能的影响。结果：每毫升海藻酸盐溶液中出现 20 毫克（1% v/v）的微球浓度，对应 15-20 百万个细胞才能成为最佳配置。生物反应器中珠子的填充率可达60%。四个 250 mL 生物反应器约占肝脏中肝细胞的 15%，这是体外肝脏供应的合理目标。结论：增加珠子密度明显保持了具有不同成分的血浆的流化床的性能，没有任何从生物反应器中释放的风险。海藻酸盐溶液中 1% (v/v) 浓度的微球不会导致机械或生物行为的任何改变。因此，该浓度可应用于大规模封装生物质的生产，以便在人体规模临床前研究中进一步使用 Suppliver 设置。
Background: Our team previously designed and validated a new bioartificial liver (BAL) called Suppliver based on a Prismaflex (TM) device, including fluidized bed bioreactors hosting alginate-encapsulated hepatocytes. To ensure correct fluidization within the bioreactor, the beads need to become heavier with the addition of inert glass microspheres.Methods: In this study, we assessed the impact of this additional component on the bead production process, bed fluidization, mass transfer and the mechanical properties of the beads, as well as cell viability and basic metabolic function.Results: A concentration of 20 mg (1% v/v) of microspheres for 15-20 million cells per milliliter of alginate solution appears to be the best configuration. The filling ratio for the beads in the bioreactors can reach 60%. Four 250-mL bioreactors represent approximately 15% of the hepatocytes in a liver, which is a reasonable target for extracorporeal liver supply.Conclusions: Increasing bead density clearly maintained the performances of the fluidized bed with plasma of different compositions, without any risk of release out of the bioreactor. A 1% (v/v)-concentration of microspheres in alginate solution did not result in any alteration of the mechanical or biological behavior. This concentration can thus be applied to the production of large-scale encapsulated biomass for further use of the Suppliver setup in human scale preclinical studies.