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
Externally publishedYes

Fingerprint

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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