A microfluidic 3D hepatocyte chip for hepatotoxicity testing of nanoparticles

Nanomedicine (Lond). 2019 Aug;14(16):2209-2226. doi: 10.2217/nnm-2019-0086. Epub 2019 Jun 10.

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.

Keywords: 3D hepatocyte chip; albumin; nanotoxicology; primary rat hepatocytes; superparamagnetic iron oxide nanoparticles (SPION); urea.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques / methods*
  • Cells, Cultured
  • Female
  • Hepatocytes / cytology*
  • Microfluidics / methods*
  • Nanoparticles / chemistry*
  • Rats
  • Urea / metabolism

Substances

  • Urea