Hydrogel-Based Spheroid Models of Glioblastoma for Drug Screening Applications

Glioblastoma multiforme (GBM) is the most aggressive brain tumor, with median patient survival of 12-15 months even after treatment. To facilitate basic research as well as treatment development, bioengineered GBM models that adequately recapitulate aspects of the in vivo tumor microenvironment are greatly needed. Multicellular spheroids are a well-accepted model in tumor biology as well as drug screening because they recapitulate many of the solid tumor characteristics, such as hypoxic core and cell-cell communication. There are multiple approaches for growing GBM cells into tumor spheroids - non-adherent plastic dishes, hanging drop, bioreactors, and hydrogels, amongst others. Suspension spheroid models offer ease of growth, uniformity, and overall lower cost, but neglect the cell-matrix interactions, while hydrogel-based spheroids capture cell-matrix interactions and allow co-cultures with stromal cells. In this review, we summarize various approaches to fabricate GBM spheroid models as well as GBM spheroid characteristics and chemotherapeutic responsiveness as a function of hydrogel matrix encapsulation and properties, in order to advance therapies.