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A microfluidic 3D hepatocyte chip for hepatotoxicity testing of nanoparticles

Authors
  • Li, Lei1, 2
  • Gokduman, Kurtulus1
  • Gokaltun, Aslihan1, 3
  • Yarmush, Martin L1, 4
  • Usta, Osman Berk1
  • 1 Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Shriners Hospitals, Boston, MA 02114, USA
  • 2 CAS Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, PR China
  • 3 Department of Chemical Engineering, Hacettepe University, 06800, Beytepe, Ankara, Turkey
  • 4 Rutgers State University, Department of Biomedical Engineering, Piscataway, NJ 08854, USA
Type
Published Article
Journal
Nanomedicine
Publisher
Future Medicine
Publication Date
Jun 10, 2019
Volume
14
Issue
16
Pages
2209–2226
Identifiers
DOI: 10.2217/nnm-2019-0086
PMID: 31179822
PMCID: PMC7006797
Source
PubMed Central
Keywords
License
Unknown

Abstract

Aim: To develop a practical microfluidic 3D hepatocyte chip for hepatotoxicity testing of nanoparticles using proof of concept studies providing first results of the potential hepatotoxicity of superparamagnetic iron oxide nanoparticles (SPION) under microfluidic conditions. Methods: A microfluidic 3D hepatocyte chip with three material layers, which contains primary rat hepatocytes, has been fabricated and tested using different concentrations (50, 100 and 200 μg/ml) of SPION in 3-day (short-term) and 1-week (long-term) cultures. Results: Compared with standard well plates, the hepatocyte chip with flow provided comparable viability and significantly higher liver-specific functions, up to 1 week. In addition, the chip recapitulates the key physiological responses in the hepatotoxicity of SPION. Conclusion: Thus, the developed 3D hepatocyte chip is a robust and highly sensitive platform for investigating hepatotoxicity profiles of nanoparticles.

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