Developing 3D Printing Models of Brain Tumors

AIMS To succeed in clinical trials for glioblastoma we need in vitro models capable of more faithfully replicating dis- ease biology and more accurately predicting patient drug responses. To this end, new bioprinting technologies have the potential to biofabricate clinically relevant biomimetic tissues which can accelerate drug discovery and additionally serve as a platform for personalized medicine. METHOD We evaluated the effect of individual biomaterials and combinations of biomaterials, including decellularised pig brain extracellular matrix (dECM), fibrin, gelatin-methacryloyl (GelMA), hyaluronic acid-methacrylate (HAMA), Matrigel and alginate, on the proliferation and invasion of aggressive brain cancer cells (U87) in vitro. Cell viability was assessed using propidium iodide. Invasiveness was studied employing confocal microscopy. Data generated from Z-stacks was analysed using ImageJ to determine the size and circularity of cells. RESULTS Although Matrigel supports rapid cell proliferation and invasion, it has mechanical properties unsuited to bio- printing. In contrast, HAMA displays a pronounced shear-thinning behaviour and rapid controllable photo- crosslinking. Combinations of HAMA-fibrin provided results comparable to those seen with Matrigel or HAMA- Matrigel. However, high levels of crosslinking affected these biomaterial mixtures, resulting in a decreased ability of cells to grow and spread. CONCLUSIONS Initial results indicate that the addition of fibrin to HAMA promoted the growth and spreading of U87 cells. In further work, we aim to improve our printed constructs by including porcine brain dECM, microglia and recently established cell lines from paediatric patients. The project will test whether these bioprinted models can provide drug testing data with closer results to human disease than current, simpler alternatives.