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

83 Citations (Scopus)

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 1 2013

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Military electronic countermeasures
Hyaluronic acid
Chitosan
Hyaluronic Acid
Glioblastoma
Scaffolds
Tumors
Screening
Nestin
Neoplasms
Tumor Microenvironment
Oncology
Chemotherapy
Early Detection of Cancer
Pharmaceutical Preparations
Polyelectrolytes
Cultured Cells
Up-Regulation
Therapeutics
Clinical Trials

Keywords

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

ASJC Scopus subject areas

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

Cite this

Florczyk, S. J., Wang, K., Jana, S., Wood, D. L., Sytsma, S. K., Sham, J. G., ... Zhang, M. (2013). Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM. Biomaterials, 34(38), 10143-10150. https://doi.org/10.1016/j.biomaterials.2013.09.034

Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM. / Florczyk, Stephen J.; Wang, Kui; Jana, Soumen; Wood, David L.; Sytsma, Samara K.; Sham, Jonathan G.; Kievit, Forrest M; Zhang, Miqin.

In: Biomaterials, Vol. 34, No. 38, 01.12.2013, p. 10143-10150.

Research output: Contribution to journalArticle

Florczyk, SJ, Wang, K, Jana, S, Wood, DL, Sytsma, SK, Sham, JG, Kievit, FM & Zhang, M 2013, 'Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM', Biomaterials, vol. 34, no. 38, pp. 10143-10150. https://doi.org/10.1016/j.biomaterials.2013.09.034
Florczyk, Stephen J. ; Wang, Kui ; Jana, Soumen ; Wood, David L. ; Sytsma, Samara K. ; Sham, Jonathan G. ; Kievit, Forrest M ; Zhang, Miqin. / Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM. In: Biomaterials. 2013 ; Vol. 34, No. 38. pp. 10143-10150.
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