Fabrication and Characterization of Chitosan–Hyaluronic Acid Scaffolds with Varying Stiffness for Glioblastoma Cell Culture

• Published in: Advanced healthcare materials Vol. 7; no. 15; pp. e1800295 - n/a
• Main Authors: Erickson, Ariane E., Lan Levengood, Sheeny K., Sun, Jialu, Chang, Fei‐Chien, Zhang, Miqin
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-08-2018
• Subjects: Brain cancer; Cancer; Cell culture; Cell proliferation; Chitosan; Drug resistance; Fabrication; Gene expression; Glioblastoma; Glioblastoma cells; Hyaluronic acid; Invasiveness; Kinases; Malignancy; Morphology; Phenotypes; Polyelectrolytes; Reversion; Scaffolds; Spheroids; Statistical analysis; Stiffness; Temozolomide; tumor models; Tumors; chitosan; glioblastoma; scaffolds; tumor models; hyaluronic acid
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201800295

The invasive and recurrent nature of glioblastoma multiforme (GBM) is linked to a small subpopulation of cancer cells, which are self‐renewing, resistant to standard treatment regimens, and induce formation of new tumors. Matrix stiffness is implicated in the regulation of cell proliferation, drug resistance, and reversion to a more invasive phenotype. Therefore, understanding the relationship between matrix stiffness and tumor cell behavior is vital to develop appropriate in vitro tumor models. Here, chitosan–hyaluronic acid (CHA) polyelectrolyte complex scaffolds are fabricated with statistically significant stiffness variances to characterize the effect of scaffold stiffness on morphology, proliferation, drug resistance, and gene expression in human glioblastoma cells (U‐87 MG). All scaffolds support GBM proliferation over a 12‐day culture period, yet larger spheroids are observed in scaffolds with higher stiffness. Additionally, GBM cells cultured in stiffer CHA scaffolds prove significantly more resistant to the common chemotherapeutic temozolomide. Moreover, the stiffer 8% CHA scaffolds exhibit an increase in expression of drug resistance and invasion related genes compared to 2D culture. CHA scaffolds present a tunable microenvironment for enhanced tumor cell malignancy and may provide a valuable in vitro microenvironment for studying tumor progression and screening anticancer therapies.
Porous chitosan and hyaluronic acid (CHA) scaffolds can support growth and proliferation of glioblastoma cells. CHA scaffolds regulate cell morphology changes from small cell aggregates to tumor spheroids on scaffolds with varying stiffness ranging from normal brain tissue to tumor tissue. Cells on higher stiffness scaffolds have increased drug resistance and increased expression of drug resistance, hypoxia, and invasion‐related genes.