Neuroblastoma (NB) is the most common extracranial tumor in children and results in significant morbidity and mortality. A deeper understanding of the tumor microenvironment (TME) of NB remains an active area of research but lacks reliable and biomimetic models. In this study, a 3D bioprinting approach is used in combination with NB spheroids to create an in vitro vascular model of NB to study tumor function within an endothelialized microenvironment. A gelatin methacryloyl (gelMA) bioink is used to create multichannel cubic tumor analogues with high print fidelity and mechanical tunability. Human NB spheroids and umbilical vein endothelial cells (HUVECs) are integrated into the biologically engineered gelMA and co-cultured under static and dynamic conditions, showing high levels of survival and growth. Quantification of NB-EC integration and tumor cell migration suggests increased aggressive behaviour of NB when cocultured with HUVECs in bioengineered endothelialized models. This model also allows the assessment of metabolic, cytokine, and gene expression profiles of NB spheroids under different TME conditions. These results create a high-throughput research platform to study TME-mediated cellular-molecular mechanisms of tumor growth, aggression, and response to therapy.
A 3D bioprinted in vitro model of neuroblastoma recapitulates dynamic tumor-endothelial cell interactions contributing to solid tumor aggressive behavior
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