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

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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.

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Acknowledgements

Support from the Center for Integration of Medicine and Innovative Technology (US Army DAMD17-02-2-0006) is gratefully acknowledged. We thank Dr. Irina Pomerantseva for critically reading of the manuscript.

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Authors and Affiliations

  1. Department of Surgery, Massachusetts General Hospital, Boston, MA, USA

    Amedeo Carraro, Wen-Ming Hsu, Katherine M. Kulig, Wing S. Cheung, Joseph P. Vacanti & Craig Neville

  2. Department of Surgical and Gastroenterological Sciences, University of Padua, School of Medicine, Padova, Italy

    Amedeo Carraro

  3. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

    Wen-Ming Hsu

  4. Harvard Medical School, Boston, MA, USA

    Mark L. Miller, Eric F. Swart, Joseph P. Vacanti & Craig Neville

  5. Biomedical Engineering Center, Charles Stark Draper Laboratory, Cambridge, MA, USA

    Eli J. Weinberg & Jeffrey T. Borenstein

  6. Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA

    Mohammad Kaazempur-Mofrad

  7. Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street CPZN-4809, Boston, MA, 02114, USA

    Amedeo Carraro, Wen-Ming Hsu, Katherine M. Kulig, Wing S. Cheung, Joseph P. Vacanti & Craig Neville

Authors
  1. Amedeo Carraro
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  2. Wen-Ming Hsu
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  3. Katherine M. Kulig
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  4. Wing S. Cheung
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  5. Mark L. Miller
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  6. Eli J. Weinberg
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  7. Eric F. Swart
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  8. Mohammad Kaazempur-Mofrad
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  9. Jeffrey T. Borenstein
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  10. Joseph P. Vacanti
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  11. Craig Neville
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Corresponding author

Correspondence to Craig Neville.

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Carraro, A., Hsu, WM., Kulig, K.M. et al. In vitro analysis of a hepatic device with intrinsic microvascular-based channels. Biomed Microdevices 10, 795–805 (2008). https://doi.org/10.1007/s10544-008-9194-3

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  • DOI: https://doi.org/10.1007/s10544-008-9194-3

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