Crafting Mindscapes of the Brain

         

The human brain buzzes with intricate neural highways firing signals between neurons. Understanding these networks is crucial for deciphering brain health and disease, yet existing models have had varied success. This inspired Su-ChunZhang, a stem cell biologist at Duke-National University of Singapore Medical School and the University of Wisconsin-Madison, to design a platform to reliably model functional neural tissue. 

Zhang and his team developed a bioink composed of proteins and gel polymers to 3D print brain tissues. Their findings, published in Cell Stem Cell, provide a promising tool for researchers to design and study customized brains.¹ “We developed the technology to guide human stem cells to many kinds of nerve cells, much like having all the materials to cook a dish. We just need to put them all together,” explained Zhang.

3D bioprinting enables researchers to select cell types and spatial distributions to replicate brain tissue. Traditional 3D bioprinting stacks cell layers vertically, but these structures often fail to support proper cellular connectivity.² Zhang's team crafted a Goldilocks bioink using a fibrin hydrogel that provided optimal stiffness for cell structural integrity and survival. They horizontally layered neurons and astrocytes in a pattern resembling the cerebral cortex and striatum, aiming to create functional neural circuits.  

Zhang anticipated random neural connections from artificial printing, but the tissues behaved just like they do in the brain. Electrophysiological recordings and calcium imaging showed consistent neuronal communication within and across brain regions.

Massimiliano Caiazzo, a neurobiologist at Utrecht University who was not involved in the study, said, “It would be interesting to create an in vitro synaptic circuit that you can tune for disease modeling.” 

“Because you can essentially control the composition of the tissue, we can artificially design models that exist and may not exist in our brain to observe how these cells talk to each other,” Zhang noted.