Flat brain
A study conducted by an international team from the Autonomous University of Madrid and the Technical University of Denmark demonstrated the technology of creating flat brain organoids. Flat frames printed on a 3D printer allowed to significantly increase the size of the brain organoid, and after 20 days, self-generated folding, similar to the convolutions of the human brain, was observed in them.
The researchers' work was aimed at eliminating a number of shortcomings of existing brain organoids. The absence of vascularization and insufficient diffusion of nutrients and oxygen lead to the appearance of a necrotic nucleus in organoids larger than 500 microns. In an attempt to solve this problem, brain organoids were vascularized: the inclusion of endothelial cells in the system increased the complexity of the model, but the generated vascular structures did not demonstrate any functionality – there was no blood flow in vitro. The authors of the study suggested that it is possible to solve this problem by applying bioengineering methods.
By cultivating brain organoids on a polycaprolactone (PCL) scaffold, the researchers were able to make them flat. The flat brain organoids constructed in this way have favorable conditions for diffusion, and therefore the tissues are better supplied with oxygen and nutrients. The transition from a spherical shape to a flat one also leads to a significant increase in the ratio of the surface of brain organoids to their volume. In addition, flat brain organoids have the potential to create biologically relevant systems due to the complexity of the models they allow to make. Ensuring the long-term viability of these models is the main goal of this field of research; flat organoids solve the problem due to their shape, which improves vascularization and prevents necrosis.
Three-dimensional printing made it possible to produce complex frames with high accuracy and reproducibility. The 3D frame allows you to adjust the size, density and thickness of the tissue of brain organoids.
The created model also demonstrated the consistent formation of neuroepithelial folding, resembling the convolutions of the human brain. It spontaneously appeared on about the 20th day of cultivation. Convolutions increase the surface area of the model in the same way as in the process of human brain development.
The authors note that although organoids do not reproduce the exact anatomy of the human brain, they are an important step towards its imitation: tissue-equivalent models, such as these organoids, can exclude the use of animal models in drug toxicity studies and understanding the progression of diseases.
The human brain is the most complex organ of the body, and because of its inaccessibility, scientists still lack scientific knowledge about brain development and diseases. Research with animals is ethically limited and should be gradually minimized. The protocol for creating flat brain organoids with convolutions is another step towards creating a stable and reliable model of the human brain.
Article by T.S.P.Rothenbücher et al. Next generation human brain models: engineered Flat brain organoids grown on 3D-printed scaffolds show intrinsic gyrification
organoids featuring gyrification is published in the journal Biofabrication.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert materials: Flat brain organoids grown on 3D-printed scaffolds show intrinsic gyrification.