Hyaluronic Acid-Coated Aligned Nanofibers for the Promotion of Glioblastoma Migration

Abstract

The propensity of glioblastoma multiforme (GBM) cells to migrate along white matter tracts and blood vessels suggests that topographical cues associated with brain parenchyma greatly influence GBM motility and invasion. In vitro cell culture platforms that mimic the physical and biochemical characteristics of brain tissue are needed to develop biologically relevant GBM migration models for the development of anticancer therapies. Here, we fabricated highly aligned chitosan-polycaprolactone (C-PCL) polyblend nanofibers coated with hyaluronic acid (HA), a glycosaminoglycan commonly found in the brain, to simulate the structure and biochemistry of native brain tissue. The influence of topography on GBM cell behavior was apparent on both HA-coated and uncoated nanofibers where cells aligned axially along nanofibers and displayed an elongated morphology associated with migration. Time lapse imaging revealed that migrating cells on nanofibers were less likely to divide, suggesting a shift to a mesenchymal-like phenotype. Cells cultured on nanofibers coated with 0.5% HA achieved the highest migratory speed relative to uncoated nanofibers and 2D adherent cultures on polystyrene plates. Further, cells on nanofibers were more resistant to cell death, after exposure to the common chemotherapeutic Temozolomide than cells grown on 2D polystyrene plates. These results indicate that HA-coated nanofibers are a promising substrate for characterization of GBM migration and investigation of novel therapies.