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 language | English (US) |
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Pages (from-to) | 10143-10150 |
Number of pages | 8 |
Journal | Biomaterials |
Volume | 34 |
Issue number | 38 |
DOIs | |
State | Published - Dec 2013 |
Externally published | Yes |
Keywords
- Cancer stem cell
- Glioma
- Invasion
- Multidrug resistance
- Spheroid
ASJC Scopus subject areas
- Mechanics of Materials
- Ceramics and Composites
- Bioengineering
- Biophysics
- Biomaterials