Researchers produce first functional 3D printed human brain tissue

A team of scientists from the University of Wisconsin-Madison has developed the first 3D printed brain tissue capable of growing and functioning like typical brain tissue.

This is an achievement with important implications for scientists who study the brain and work on treatments for a wide range of neurological and neurodevelopmental disorders, such as Alzheimer’s disease and Parkinson’s disease.

“This could be an extremely powerful model to help us understand how brain cells and parts of the brain communicate in humans,” says Su-Chun Zhang, professor of neuroscience and neurology at the Waisman Center at UW-Madison . “This could change the way we view stem cell biology, neuroscience and the pathogenesis of many neurological and psychiatric disorders.”

Printing methods have limited the success of previous attempts to print brain tissue, according to Zhang and Yuanwei Yan, a scientist in Zhang’s lab. The group behind the new 3D printing process describes its method in the journal Stem cell.

Instead of using the traditional 3D printing approach of stacking layers vertically, the researchers opted for a horizontal approach. They placed brain cells, neurons grown from induced pluripotent stem cells, in a softer “bio-ink” gel than previous attempts had used.

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

The cells are arranged next to each other like pencils placed next to each other on a table.

“Our tissues remain relatively thin, which allows neurons to easily obtain enough oxygen and sufficient nutrients from the growth medium,” Yan explains.

The results speak for themselves: cells can communicate with each other. Printed cells pass through the medium to form connections within each printed layer as well as across layers, forming networks comparable to the human brain. Neurons communicate, send signals, interact with each other via neurotransmitters and even form real networks with support cells added to the printed fabric.

“We printed the cerebral cortex and striatum and what we found was quite striking,” says Zhang. “Even when we printed different cells belonging to different parts of the brain, they were still able to communicate with each other in a very special and specific way.”

The printing technique offers precision – control over cell types and arrangements – not found in brain organoids, miniature organs used to study the brain. Organoids grow with less organization and control.

“Our lab is very special in that we are able to produce just about any type of neurons at any time. We can then assemble them at any time and in any way we want,” says Zhang. “Because we can print tissue as soon as we design it, we can have a defined system to look at how our human brain network works. We can look very specifically at how nerve cells communicate with each other under certain conditions, because we can print exactly what we want.”

This specificity brings flexibility. Printed brain tissue could be used to study signaling between Down syndrome cells, interactions between healthy tissues and neighboring tissues affected by Alzheimer’s disease, test new drug candidates or even observe brain growth.

“In the past, we have often looked at one thing at a time, which means we often forget some essential components. Our brain works in networks. We want to print brain tissue this way because cells don’t work through them This is how our brain works and we have to study it together to really understand it,” explains Zhang.

“Our brain tissue could be used to study almost every major aspect of what many people at the Waisman Center are working on. It can be used to examine the molecular mechanisms that underlie brain development, human development, disorders development, neurodegenerative disorders, etc. “.

The new printing technique should also be accessible to many laboratories. It does not require bioprinting equipment or special culture methods to maintain healthy tissue, and can be studied in depth using microscopes, standard imaging techniques, and already common electrodes in this domain.

The researchers would, however, like to explore the potential of specialization, by further improving their bio-ink and refining their equipment to enable specific orientations of cells in their printed tissues.

“At present, our printer is marketed on a tabletop,” explains Yan. “We can make specialized improvements to help us print specific types of brain tissue on demand.”