Bioprinting a novel glioblastoma tumor model using a fibrin-based bioink for drug screening

Abstract

Glioblastoma multiforme (GBM), a deadly primary brain cancer, exhibits invasive proliferation into healthy brain tissue. Currently, novel treatment methods are being investigated as possible alternatives to the current standard of care for the disease, which consists of tumor resection followed by additional treatment to prevent tumor recurrence. However, investigation into novel GBM treatments remains hindered by the limited ability of preclinical disease models to accurately assess drug effectiveness and toxicity. Recent developments in the fields of biotechnology and tissue engineering have made 3D bioprinting of hydrogel-based biomaterial scaffolds a feasible method for rapidly producing an accurate in vitro model for glioblastoma, custom designed to the needs of the investigator. Here, we developed a novel fibrin-based 3D printed GBM model for cellular characterization and drug screening using an Aspect Biosystems RX1 bioprinter. Their Lab-On-a-Printer™ microfluidic print head minimizes shear stress, allowing for effective printing of delicate neural tissue. Printed glioblastoma cell–laden structures displayed high levels of cell viability for 12 days following initial printing. Furthermore, printed cells spontaneously formed spheroids with upregulated levels of the proteins CD133 and DCX markers associated with cancer stem cells and metastatic invasiveness, respectively. Printed scaffolds were then treated with a novel chemical treatment method previously tested in 2D culture and showed significant resistance, indicating the 3D printed glioblastoma model's potential as a more accurate representation of the in vivo response to drug treatment.