Hepatocyte encapsulation for enhanced cellular functions

Hepatocyte encapsulation for enhanced cellular functions
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DOI:
10.1089/107632700750022134
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发表时间:
2000-10-01
期刊:
影响因子:
--
通讯作者:
Yu, H
Yu, H
中科院分区:
生物2区
文献类型:
--
作者:
Chia, SM;Leong, KW;Yu, H

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高效的生物人工肝辅助装置可以维持急性肝衰竭患者的生命。在生物反应器设计的不同配置中,肝细胞包封具有满足装置的大多数要求的重要特征。我们已经封装在一个两层的聚合物膜的复合凝聚,使用一个简单的设置和增强的细胞功能比单层对照高出三倍。这些功能性肝细胞的微囊具有2- 3-μ m的合成聚合物外层和带正电荷的改性胶原蛋白内层,所述合成聚合物具有25%的甲基丙烯酸2-羟乙酯、25%的甲基丙烯酸和50%的甲基丙烯酸甲酯,所述带正电荷的改性胶原蛋白作为增强的细胞功能的合适基质。微囊仅可渗透至白蛋白的小分子,应允许营养素、氧、生长因子和代谢物的不受阻碍的交换,但防止免疫系统的免疫球蛋白的攻击,并且未观察到胶原的“皮肤效应”。用纳米压痕法测量的微胶囊的机械性能表明,该微胶囊应适用于生物人工肝辅助装置。
An efficient bioartificial liver-assisted device can sustain the lives of patients with acute liver failure. Among different configurations of the bioreactor design, hepatocyte encapsulation has important features that satisfy most requirements of the device. We have encapsulated rat hepatocytes in a two-layer polymeric membrane by complex coacervation using a simple setup and demonstrated enhanced cellular functions up to three times higher than those of the monolayer control. These microcapsules of the functioning hepatocytes have a 2- to 3-mum outer layer of synthetic polymer with 25% 2-hydroxyethyl methaerylate, 25% methacrylic acid, and 50% methyl methacrylate and an inner layer of positively charged modified collagen as a suitable substrate for the enhanced cellular functions. Permeable only to small molecules up to albumin, the microcapsules should allow unimpeded exchange of nutrients, oxygen, growth factors, and metabolites but prevent attack by immunoglobulins of the immune system, and no "skin effect" of the collagen has been observed. Mechanical properties of the microcapsules measured with a nano-indentation method suggest that the microcapsules should be suitable for use in a bioartificial liver-assisted device.