Micropatterned agarose scaffolds covalently modified with collagen for culture of normal and neoplastic hepatocytes

Authors

  • Angela Y. Au,

    1. Department of Research and Development, Nutramax Laboratories, Inc., Edgewood, Maryland
    2. Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, New York
    Search for more papers by this author
  • Julie M. Hasenwinkel,

    1. Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, New York
    Search for more papers by this author
  • Carmelita G. Frondoza

    Corresponding author
    1. Department of Research and Development, Nutramax Laboratories, Inc., Edgewood, Maryland
    2. Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, Maryland
    3. College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi
    • Department of Research and Development, Nutramax Laboratories, Inc., Edgewood, Maryland
    Search for more papers by this author

  • How to cite this article: Au AY, Hasenwinkel JM, Frondoza CG. 2012. Micropatterned agarose scaffolds covalently modified with collagen for culture of normal and neoplastic hepatocytes. J Biomed Mater Res Part A 2012:100A:342–352.

Abstract

Anchorage-dependent cells including hepatocytes, the main functional cellular constituent comprising liver tissue, require a substrate for cell adhesion when cultured outside their native tissue. The challenge with hepatocyte culture is that material substrates and designs supporting hepatocyte attachment, phenotype, and function are not readily available. Our laboratory previously published that type I collagen found in the liver extracellular matrix supports hepatocyte culture. We hypothesized that micropatterned agarose with a coating of collagen covalently bound to the surface would facilitate hepatocyte adhesion and phenotype. To test this hypothesis, primary canine hepatocytes and neoplastic human HepG2 hepatocellular carcinoma cells were cultured on these substrates. Hepatocyte adhesion was dependent on the cell type and also the micropattern design. Viable normal and neoplastic hepatocytes attached to the microchannel troughs rather than on the ridges. In contrast, hepatocyte adhesion on the microcircular patterns was similar to control agarose as cells did not sense differences in surface topology on these substrates. Neoplastic cells exhibited a distinct difference in growth behavior following 7 days in culture on the microchannel patterns, exhibiting aberrant proliferation relative to normal hepatocytes which did not proliferate. Our results suggest that patterned microchannel agarose may be useful to evaluate hepatoprotective and noxious agents. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.

Ancillary