A scalable 3D-printed brain tumour model for high-throughput screening glioblastoma biology and drug response
Glioblastoma (GBM) is a highly aggressive brain tumour characterized by its rapid infiltrative growth patterns, marked intra- and inter-tumoural heterogeneity, and resistance to conventional treatments. GBM has a median overall survival of 15 months and a 5-year survival rate of approximately 5%. Current treatment modalities, including surgery and chemoradiotherapy, have shown limited success. To address the need for more effective therapeutic strategies and a deeper understanding of GBM biology, we utilised droplet printing technology to fabricate a high-throughput 3D brain tumour model. We first optimized the printability of the GBM cell-laden gelatin methacrylate (GelMA) bioink, tailoring its mechanical properties to mimic the stiffness of human brain tissue. Next, we employed metabolic and immunofluorescence assays to investigate the response of the printed GBM droplets to the standard-of-care chemotherapeutic agent temozolomide (TMZ). Furthermore, using digital droplet PCR (ddPCR), we assessed the expression of microRNAs typical for paediatric GBM (miR-490, miR-876-3p, miR-876-5p, miR-448, miR-137, and miR-501-3p), with miR-191-5p used as the endogenous control. Our approach provides proof-of-concept for high-throughput screening of GBM drug response. Moreover, our 3D-printed brain tumour model could be used for patient-personalised tumour screening, encompassing theranostics for GBM diagnostics, treatment, and monitoring.
