Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function

Aleksander Skardal, Leona Smith, Shantaram Bharadwaj, Anthony Atala, Shay Soker, Yuanyuan Zhang

Research output: Contribution to journalArticle

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Abstract

Despite recent advances in biomaterial science, there is yet no culture system that supports long-term culture expansion of human adult hepatocytes, while preserving continued function Previous studies suggested that acellular liver extracellular matrix (ECM), employed as a substrate, improved proliferation and function of liver cells Here we investigated whether extracts prepared from acellular liver ECM (liver ECM extract, LEE), or from whole (fresh) liver tissue (liver tissue extract, LTE), could be combined with collagen Type I, hyaluronic acid (HA), or heparin-conjugated HA (HP) hydrogels to enhance survival and functional output of primary human hepatocytes The liver-specific semi-synthetic ECMs (sECMs) were prepared by incorporating LEE or LTE into the gel matrices Subsequently, primary human hepatocytes were maintained in sandwich-style hydrogel cultures for 4 weeks Progressive increase in hepatocyte metabolism was observed in all HA and HP groups Hepatocytes cultured in HA and HP hydrogels containing LEE or LTE synthesized and secreted steady levels of albumin and urea and sustained cytochrome p450-dependent drug metabolism of ethoxycoumarin Collectively, these results indicate that customized HA hydrogels with liver-specific ECM components may be an efficient method for expansion human hepatocytes in vitro for cell therapy and drug and toxicology screening purposes.

Original languageEnglish (US)
Pages (from-to)4565-4575
Number of pages11
JournalBiomaterials
Volume33
Issue number18
DOIs
StatePublished - Jun 1 2012

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Keywords

  • Extracellular matrix
  • Growth factors
  • Heparin
  • Hepatocyte
  • Hyaluronic acid

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Skardal, A., Smith, L., Bharadwaj, S., Atala, A., Soker, S., & Zhang, Y. (2012). Tissue specific synthetic ECM hydrogels for 3-D in vitro maintenance of hepatocyte function. Biomaterials, 33(18), 4565-4575. https://doi.org/10.1016/j.biomaterials.2012.03.034