Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM

Stephen J. Florczyk, Kui Wang, Soumen Jana, David L. Wood, Samara K. Sytsma, Jonathan G. Sham, Forrest M. Kievit, Miqin Zhang

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Cancer therapeutics are developed through extensive screening; however, many therapeutics evaluated with 2D invitro cultures during pre-clinical trials suffer from lower efficacy in patients. Replicating the invivo tumor microenvironment invitro with three-dimensional (3D) porous scaffolds offers the possibility of generating more predictive pre-clinical models to enhance cancer treatment efficacy. We developed a chitosan and hyaluronic acid (HA) polyelectrolyte complex 3D porous scaffold and evaluated its physical properties. Chitosan-HA (C-HA) scaffolds had a highly porous network. C-HA scaffolds were compared to 2D surfaces for invitro culture of U-118MG human glioblastoma (GBM) cells. C-HA scaffold cultures promoted tumor spheroid formation and increased stem-like properties of GBM cells as evidenced by the upregulation of CD44, Nestin, Musashi-1, GFAP, and HIF-1α as compared with 2D cultures. Additionally, the invasiveness of GBM cells cultured in C-HA scaffolds was significantly enhanced compared to those grown in 2D cultures. C-HA scaffold cultures were also more resistant to chemotherapy drugs, which corresponded to the increased expression of ABCG2 drug efflux transporter. These findings suggest that C-HA scaffolds offer promise as an invitro GBM platform for study and screening of novel cancer therapeutics.

Original languageEnglish (US)
Pages (from-to)10143-10150
Number of pages8
JournalBiomaterials
Volume34
Issue number38
DOIs
StatePublished - Dec 2013

Keywords

  • Cancer stem cell
  • Glioma
  • Invasion
  • Multidrug resistance
  • Spheroid

ASJC Scopus subject areas

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

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