Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture

M. Bhattacharya, M. M. Malinen, P. Lauren, Y.-R. Lou, S. W. Kuisma, L. Kanninen, Martina Lille, A. Corlu, C. GuGuen-Guillouzo, O. Ikkala, A. Laukkanen, A. Urtti, M. Yliperttula (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

193 Citations (Scopus)


Over the recent years, various materials have been introduced as potential 3D cell culture scaffolds. These include protein extracts, peptide amphiphiles, and synthetic polymers. Hydrogel scaffolds without human or animal borne components or added bioactive components are preferred from the immunological point of view. Here we demonstrate that native nanofibrillar cellulose (NFC) hydrogels derived from the abundant plant sources provide the desired functionalities. We show 1) rheological properties that allow formation of a 3D scaffold in-situ after facile injection, 2) cellular biocompatibility without added growth factors, 3) cellular polarization, and 4) differentiation of human hepatic cell lines HepaRG and HepG2. At high shear stress, the aqueous NFC has small viscosity that supports injectability, whereas at low shear stress conditions the material is converted to an elastic gel. Due to the inherent biocompatibility without any additives, we conclude that NFC generates a feasible and sustained microenvironment for 3D cell culture for potential applications, such as drug and chemical testing, tissue engineering, and cell therapy.
Original languageEnglish
Pages (from-to)291-298
Number of pages8
JournalJournal of Controlled Release
Issue number3
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed
Event12th European Symposium of Controlled Drug Delivery - Egmond aan Zee, Netherlands
Duration: 4 Apr 20126 Apr 2012


  • 3D cell culture
  • Hepatocyte
  • Nanocellulose
  • Nanofiber
  • Plant-derived cellulose

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  • Cite this

    Bhattacharya, M., Malinen, M. M., Lauren, P., Lou, Y-R., Kuisma, S. W., Kanninen, L., Lille, M., Corlu, A., GuGuen-Guillouzo, C., Ikkala, O., Laukkanen, A., Urtti, A., & Yliperttula, M. (2012). Nanofibrillar cellulose hydrogel promotes three-dimensional liver cell culture. Journal of Controlled Release, 164(3), 291-298.