Porous chitosan-hyaluronic acid scaffolds as a mimic of glioblastoma microenvironment ECM.
Cancer therapeutics are developed through extensive screening; however, many therapeutics evaluated with 2D in vitro cultures during pre-clinical trials suffer from lower efficacy in patients. Replicating the in vivo tumor microenvironment in vitro 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 in vitro culture of U-118 MG 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 in vitro GBM platform for study and screening of novel cancer therapeutics.
Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.
Stephen J
SJ
Florczyk
Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.
Kui
K
Wang
Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.
Soumen
S
Jana
Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.
David L
DL
Wood
Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.
Samara K
SK
Sytsma
Department of Surgery, University of Washington, Seattle, WA, 98195, USA.
Jonathan
J
Sham
Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.|Department of Neurological Surgery, University of Washington, Seattle, WA, 98195, USA.
Forrest M
FM
Kievit
Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.|Department of Neurological Surgery, University of Washington, Seattle, WA, 98195, USA.
Miqin
M
Zhang
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048271:Chitosan / Q000737:chemistry*; D005109:Extracellular Matrix / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D016062:Porosity; D017550:Spectroscopy, Fourier Transform Infrared; D054457:Tissue Scaffolds / Q000737:chemistry*
D006820:Hyaluronic Acid; D048271:Chitosan
Cancer stem cell; Glioma; Invasion; Multidrug resistance; Spheroid