Article

Biomedical Microdevices

, Volume 10, Issue 6, pp 795-805

First online:

In vitro analysis of a hepatic device with intrinsic microvascular-based channels

  • Amedeo CarraroAffiliated withDepartment of Surgery, Massachusetts General HospitalDepartment of Surgical and Gastroenterological Sciences, University of Padua, School of MedicineCenter for Regenerative Medicine, Massachusetts General Hospital
  • , Wen-Ming HsuAffiliated withDepartment of Surgery, Massachusetts General HospitalDepartment of Surgery, National Taiwan University HospitalCenter for Regenerative Medicine, Massachusetts General Hospital
  • , Katherine M. KuligAffiliated withDepartment of Surgery, Massachusetts General HospitalCenter for Regenerative Medicine, Massachusetts General Hospital
  • , Wing S. CheungAffiliated withDepartment of Surgery, Massachusetts General HospitalCenter for Regenerative Medicine, Massachusetts General Hospital
  • , Mark L. MillerAffiliated withHarvard Medical School
  • , Eli J. WeinbergAffiliated withBiomedical Engineering Center, Charles Stark Draper Laboratory
  • , Eric F. SwartAffiliated withHarvard Medical School
  • , Mohammad Kaazempur-MofradAffiliated withDepartment of Bioengineering, University of California, Berkeley
  • , Jeffrey T. BorensteinAffiliated withBiomedical Engineering Center, Charles Stark Draper Laboratory
    • , Joseph P. VacantiAffiliated withDepartment of Surgery, Massachusetts General HospitalHarvard Medical SchoolCenter for Regenerative Medicine, Massachusetts General Hospital
    • , Craig NevilleAffiliated withDepartment of Surgery, Massachusetts General HospitalHarvard Medical SchoolCenter for Regenerative Medicine, Massachusetts General Hospital Email author 

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Abstract

A novel microfluidics-based bilayer device with a discrete parenchymal chamber modeled upon hepatic organ architecture is described. The microfluidics network was designed using computational models to provide appropriate flow behavior based on physiological data from human microvasculature. Patterned silicon wafer molds were used to generate films with the vascular-based microfluidics network design and parenchymal chamber by soft lithography. The assembled device harbors hepatocytes behind a nanoporous membrane that permits transport of metabolites and small proteins while protecting them from the effects of shear stress. The device can sustain both human hepatoma cells and primary rat hepatocytes by continuous in vitro perfusion of medium, allowing proliferation and maintaining hepatic functions such as serum protein synthesis and metabolism. The design and fabrication processes are scalable, enabling the device concept to serve as both a platform technology for drug discovery and toxicity, and for the continuing development of an improved liver-assist device.

Keywords

Tissue engineering Hepatocytes Liver Microfabrication