First functional human brain tissue produced through 3D printing

“This could be a hugely powerful model to help us understand how brain cells and parts of the brain communicate in humans,” said Su-Chun Zhang, professor of neuroscience and neurology at UW–Madison’s Waisman Center. 

“It could change the way we look at stem cell biology, neuroscience, and the pathogenesis of many neurological and psychiatric disorders,” added Zhang in the release. 

Use of horizontal 3D printing approach

Instead of using the conventional vertical layer stacking method, the researchers followed an innovative horizontal 3D printing approach in this development.

Neurons produced from induced pluripotent stem cells were carefully put in layers utilizing a softer bio-ink gel, creating a more favorable environment for growth.

“The tissue still has enough structure to hold together but it is soft enough to allow the neurons to grow into each other and start talking to each other,” Zhang said. 

The developers mention that they deliberately maintained the tissue’s thinness to ensure optimal oxygen and nutrient intake for the neurons from the surrounding growth media.

The multilayer printing allowed the cells to form connections, resulting in networks similar to those observed in human brains.

Within these networks, neurons appeared to actively communicate by sending signals to one another. This communication occurs via neurotransmitters, chemical messengers that aid in passing signals between neurons.

“We printed the cerebral cortex and the striatum, and what we found was quite striking. Even when we printed different cells belonging to different parts of the brain, they could still talk to each other in a very special and specific way,” said Zhang in the press release.

The authors highlight that this method provides precision, allowing for control over cell types and arrangement. This feature is absent in brain organoids, which are miniature lab-grown organs created for brain research. 

This 3D print approach to emulate sophisticated communication and network development found in human brain tissue has great potential to provide insights into brain function and its disorders. 

The findings were published in the journal Cell Stem Cell.

Study abstract:

Probing how human neural networks operate is hindered by the lack of reliable human neural tissues amenable to the dynamic functional assessment of neural circuits. We developed a 3D bioprinting platform to assemble tissues with defined human neural cell types in a desired dimension using a commercial bioprinter. The printed neuronal progenitors differentiate into neurons and form functional neural circuits within and between tissue layers with specificity within weeks, evidenced by the cortical-to-striatal projection, spontaneous synaptic currents, and synaptic response to neuronal excitation. Printed astrocyte progenitors develop into mature astrocytes with elaborated processes and form functional neuron-astrocyte networks, indicated by calcium flux and glutamate uptake in response to neuronal excitation under physiological and pathological conditions. These designed human neural tissues will likely be useful for understanding the wiring of human neural networks, modeling pathological processes, and serving as platforms for drug testing.