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Author Notes:

Kelly C. Goldsmith, Email: kgoldsm@emory.edu

L.N. and J.S. contributed equally to this work as first authors. This research was funded by the NIH Grant Number R00HL127295 and Emory University School of Medicine (Pediatric Research Alliance Pilot Grant and the Dean's Imagine, Innovate and Impact (I3) Research Award) to V.S., Hyundai Hope on Wheels Young Investigator Award (Grant Number 639727) to J.S., and CURE Childhood Cancer grant to K.G.

The authors declare no conflict of interest.



  • Science & Technology
  • Physical Sciences
  • Technology
  • Chemistry, Multidisciplinary
  • Nanoscience & Nanotechnology
  • Materials Science, Multidisciplinary
  • Chemistry
  • Science & Technology - Other Topics
  • Materials Science
  • embedded 3D bioprinting
  • endothelial cell
  • neuroblastoma
  • tumor growth and invasion
  • tumor microenvironment
  • vascularized model
  • G-CSF

A 3D Bioprinted in vitro Model of Neuroblastoma Recapitulates Dynamic Tumor-Endothelial Cell Interactions Contributing to Solid Tumor Aggressive Behavior

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Journal Title:



Volume 9, Number 23


, Pages e2200244-e2200244

Type of Work:

Article | Final Publisher PDF


Neuroblastoma (NB) is the most common extracranial tumor in children resulting in substantial morbidity and mortality. A deeper understanding of the NB tumor microenvironment (TME) remains an area of active research but there is a lack of reliable and biomimetic experimental models. This study utilizes a 3D bioprinting approach, in combination with NB spheroids, to create an in vitro vascular model of NB for exploring the tumor function within an endothelialized microenvironment. A gelatin methacryloyl (gelMA) bioink is used to create multi-channel cubic tumor analogues with high printing fidelity and mechanical tunability. Human-derived NB spheroids and human umbilical vein endothelial cells (HUVECs) are incorporated into the biomanufactured gelMA and cocultured under static versus dynamic conditions, demonstrating high levels of survival and growth. Quantification of NB-EC integration and tumor cell migration suggested an increased aggressive behavior of NB when cultured in bioprinted endothelialized models, when cocultured with HUVECs, and also as a result of dynamic culture. This model also allowed for the assessment of metabolic, cytokine, and gene expression profiles of NB spheroids under varying TME conditions. These results establish a high throughput research enabling platform to study the TME-mediated cellular-molecular mechanisms of tumor growth, aggression, and response to therapy.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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