A 3D Bioprinted Cortical Organoid Platform for Modeling Human Brain Development.

The ability to promote three-dimensional (3D) self-organization of induced pluripotent stem cells into complex tissue structures called organoids presents new opportunities for the field of developmental biology. Brain organoids have been used to investigate principles of neurodevelopment and neuropsychiatric disorders and serve as a drug screening and discovery platform. However, brain organoid cultures are currently limited by a lacking ability to precisely control their extracellular environment. Here, we employed 3D bioprinting to generate a high-throughput, tunable, and reproducible scaffold for controlling organoid development and patterning. Additionally, our approach supports the co-culture of organoids and vascular cells in a custom architecture containing interconnected endothelialized channels. Printing fidelity and mechanical assessments confirm that fabricated scaffolds closely match intended design features and exhibit stiffness values reflective of the developing human brain. Using organoid growth, viability, cytoarchitecture, proliferation, and transcriptomic benchmarks, we found that organoids cultured within the bioprinted scaffold long-term are healthy and have expected neuroectodermal differentiation. Lastly, we confirmed that the endothelial cells in printed channel structures can migrate towards and infiltrate into the embedded organoids. This work demonstrates a tunable 3D culturing platform that can be used to create more complex and accurate models of human brain development and underlying diseases. This article is protected by copyright. All rights reserved.