Coaxial extrusion bioprinted shell-core hydrogel microfibers mimic glioma microenvironment and enhance the drug resistance of cancer cells.

Glioblastoma (GBM) is the most common primary malignant central nervous system tumor. The current treatment is mainly surgical resection combined with radiotherapy, chemotherapy and other comprehensive treatment methods. However, the treatment effect is unsatisfactory, the resistance of cancer cells to alkylating agent is the major reason for the recurrence of GBM. It is necessary to develop an ideal in vitro model to investigate the drug resistance of glioma cells. In this study, shell-glioma stem cell GSC23/core-glioma cell line U118 (G/U) hydrogel microfibers with high cell viability were constructed by coaxial extrusion bioprinting. It was found that core-U118 cells gradually proliferated to form fiber-like cell aggregates and the interactions between cell-cell and cell-extracellular matrix (ECM) were increased. Furthermore, compared with shell/core-U118 (U) hydrogel microfibers, the expressions of matrix metalloproteinase-2 (MMP2), MMP9, vascular endothelial growth factor receptor-2 (VEGFR2) and O6-methylguanine-DNA methyltransferase (MGMT) which are related to tumor invasion and drug resistance were significantly enhanced in G/U hydrogel microfibers. Moreover, U118 cells derived from G/U microfibers had greater drug resistance in vitro and the level of MGMT promoter methylation in G/U cultured U118 cells was significantly lower than that of U cultured cells. In summary, coaxial extrusion bioprinted G/U hydrogel microfiber is a preferable platform for mimicking glioma microenvironment, as well as for drug development and screening.