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Published Online: 9 July 2004

Use of Ultrathin Shell Microcapsules of Hepatocytes in Bioartificial Liver-Assist Device

Publication: Tissue Engineering
Volume 9, Issue Number supplement 1

Abstract

We previously encapsulated hepatocytes in ultrathin shell microcapsules and showed them to have enhanced differentiated functions over cells cultured in monolayer. Here we have used these microencapsulated hepatocytes in a bioartificial liver-assisted device (BLAD) with a rat hepatectomy model. Primary rat hepatocytes were encapsulated in 150- to 200-μm microcapsules, using an electrostatic droplet generator. The microencapsulated hepatocytes exhibited good in vitro urea synthesis activity in plasma from rats with fulminant hepatic failure (FHF). The ex vivo hemoperfusion was conducted in FHF rats by perfusing plasma at a rate of 1-2 mL/min through 1.5-2 × 108 encapsulated hepatocytes packed into a packed-bed bioreactor. Hemoperfusion with the bioreactor was initiated 5 h after operative induction of liver failure and continued for 7 h. The BLAD-treated rats showed improvements over the control groups in survival time and metabolic indicators, including ammonia and total bilirubin levels. Furthermore, expanded bed adsorption (EBA) detoxification technology using Streamline-SP resin was explored to complement the bioreactor with microencapsulated hepatocytes. In vitro experiments indicated that serum ammonia could be specifically removed in dose-dependent manner, whereas the total serum proteins were unaffected by the resin. In ex vivo experiments, hemoperfusion with the resin was initiated 3 h after operative induction of liver failure and continued for 7 h. The resin-treated rats showed obvious serum ammonia removal with no observable total blood protein and blood cell adsorption. Therefore, Streamline-SP resin can potentially be integrated into a BLAD for improved efficacy.

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Published In

cover image Tissue Engineering
Tissue Engineering
Volume 9Issue Number supplement 1August 2003
Pages: 65 - 75
PubMed: 14511471

History

Published online: 9 July 2004
Published in print: August 2003

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Tao Sun
Molecular and Biomaterials Cluster, Institute of Materials Research and Engineering, Singapore.
Melinda L.H. Chan
Department of Physiology and National University Medical Institutes, Faculty of Medicine, National University of Singapore, Singapore
Yi Zhou
Department of Chemical and Environmental Engineering, National University of Singapore, Singapore
Xi Xu
Molecular and Biomaterials Cluster, Institute of Materials Research and Engineering, Singapore
Jing Zhang
Molecular and Biomaterials Cluster, Institute of Materials Research and Engineering, Singapore.
Xuejun Lao
Molecular and Biomaterials Cluster, Institute of Materials Research and Engineering, Singapore
Xianwei Wang
Molecular and Biomaterials Cluster, Institute of Materials Research and Engineering, Singapore
Chai-Hoon Quek
Molecular and Biomaterials Cluster, Institute of Materials Research and Engineering, Singapore
Jia-Ping Chen
Department of Chemical and Environmental Engineering, National University of Singapore, Singapore
Kam W. Leong
Molecular and Biomaterials Cluster, Institute of Materials Research and Engineering, Singapore and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland.
Hanry Yu
Molecular and Biomaterials Cluster, Institute of Materials Research and Engineering, Singapore and Department of Physiology and National University Medical Institutes, Faculty of Medicine, National University of Singapore, Singapore.

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