HIF1A and glioblastoma: In the present study, we successfully developed a cost-effective, highly reproducible three-dimensional (3D) alginate–gelatin scaffold-based glioblastoma spheroid model of the U87-MG cells, which has the capacity to induce a hypoxic microenvironment through HIF-1α, resembling the heterogeneous population of actively proliferating, hypoxic, and necrotic cells found in the TMEs of GBM tumors.