Lei Li1,2, Kurtulus Gokduman1, Aslihan Gokaltun1,3, Martin L Yarmush1,4, Osman Berk Usta1. 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.
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.
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.
Entities:
Keywords:
3D hepatocyte chip; albumin; nanotoxicology; primary rat hepatocytes; superparamagnetic iron oxide nanoparticles (SPION); urea
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