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Related Experiment Video

Updated: Nov 12, 2025

Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders
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Next generation human brain models: engineered flat brain organoids featuring gyrification.

Theresa S P Rothenbücher1,2, Hakan Gürbüz3,4,2, Marta P Pereira1

  • 1Department of Molecular Biology, Autonomous University of Madrid, Center of Molecular Biology Severo Ochoa (CBMSO, UAM-CSIC), Madrid, Spain.

Biofabrication
|March 16, 2021
PubMed
Summary

Engineered flat brain organoids (efBOs) offer improved nutrient diffusion and simplified culturing for brain research. This novel approach enables customized size and self-generated gyrification, advancing in vitro human brain models for drug screening.

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Area of Science:

  • Neuroscience
  • Biotechnology
  • Bioengineering

Background:

  • Brain organoids are valuable in vitro models for human brain studies.
  • Existing models face challenges in reproducibility, nutrient diffusion, and scalability for applications like drug screening.

Purpose of the Study:

  • To engineer a novel brain organoid model with improved characteristics for neurobiological research and drug screening.
  • To address limitations of current brain organoid technology through an engineering approach.

Main Methods:

  • Culturing brain organoids on polycaprolactone scaffolds to achieve a flat morphology (engineered flat brain organoids, efBOs).
  • Utilizing a simplified protocol allowing for customizable organoid size from the outset.
  • Seeding cells onto 12x12 mm scaffolds to increase organoid size.

Main Results:

  • Engineered flat brain organoids (efBOs) exhibit enhanced diffusion, leading to better oxygen and nutrient supply and preventing necrotic cores.
  • The protocol is simplified, reproducible, and allows for scalable organoid generation.
  • Self-generated gyrification, resembling brain folding, was observed in vitro around day 20.

Conclusions:

  • Engineered flat brain organoids (efBOs) represent a significant advancement over traditional brain organoids.
  • This protocol offers a more stable, reliable, and scalable human brain model for drug screening and spatial patterning studies.
  • The intrinsic gyrification observed is a novel finding for in vitro neuronal tissue.