Gelatin methacryloyl hydrogels in the absence of a crosslinker as 3D glioblastoma multiforme (GBM)-mimetic microenvironment

Abstract

3D platforms are important for monitoring tumor progression and screening drug candidates to eradicate tumors such as glioblastoma multiforme (GBM), a malignant type of human brain tumor. Here, a new strategy is reported that exploits visible-light-induced crosslinking of gelatin where the reaction is carried out in the absence of an additional crosslinker. Visible light-induced crosslinking promotes the design of cancer microenvironment-mimetic system without compromising the cell viability during the process and absence of crosslinker facilitates the synthesis of the unique construct. Suspension and spheroid-based models of GBM are used to investigate cellular behavior, expression profiles of malignancy, and apoptosis-related genes within this unique network. Furthermore, sensitivity to an anticancer drug, Digitoxigenin, treatment is investigated in detail. The data suggest that U373 cells, in sparse or spheroid form, have significantly decreased expressions of apoptosis-activating genes, Bad, Puma, and Caspase-3, and a high expression of prosurvival Bcl-2 gene within GelMA hydrogels. Matrix-metalloproteinase genes are also upregulated within GelMA, suggesting positive contribution of gels on extracellular remodeling of cancer cells. This unique photocurable gelatin holds great potential for clinical translation of cancer research through the analysis of 3D malignant cancer cell behavior, and hence for more efficient treatment methods for GBM.