In a world first, scientists at the University of Wisconsin-Madison have successfully 3D-printed human brain tissue that can grow and function like the real thing. 

“This could be a hugely powerful model to help us understand how brain cells and parts of the brain communicate in humans,” said professor of neuroscience and neurology at the University of Wisconsin-Madison Su-Chun Zhang, the study’s senior author, in a statement. “It could change the way we look at stem cell biology, neuroscience, and the pathogenesis of many neurological and psychiatric disorders.”

The breakthrough has the potential to provide a versatile and effective tool for researchers tackling some of the biggest challenges in neuroscience today, such as the hunt for treatments for diseases like Alzheimer’s and Parkinson’s. 

3D printing technology has come on leaps and bounds in recent years, giving rise to an array of impressive applications. Whether your pet tortoise needs a set of wheels, you fancy cooking a lovely two-course meal, or you want to watch a snake-like robot growing towards the light, 3D printing can help with that. 

But despite its many uses, attempts to 3D-print brain tissue have enjoyed limited success. The innovation came when the team at UW-Madison literally decided to turn the problem on its head.

Instead of stacking layers vertically, as occurs in traditional 3D printing, they decided to work horizontally. They grew brain cells from induced pluripotent stem cells, laying them out like a row of pencils within a soft gel they call “bio-ink”.

“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,” explained Zhang, which is vital if you want your tissue to be able to grow and develop as it would within a human body.  

“Our tissue stays relatively thin and this makes it easy for the neurons to get enough oxygen and enough nutrients from the growth media,” added first author Yuanwei Yan. 

The neurons can reach through each printed layer of gel, forming links within and between them like the web of intricate connections inside the brain. They can send signals, form networks, and interact by releasing neurotransmitters. The team even added another type of cell – astrocytes – into the tissue for the neurons to interface with.

“Our lab is very special in that we are able to produce pretty much any type of neurons at any time. Then we can piece them together at almost any time and in whatever way we like,” Zhang said. 

The authors say this level of precision and control is beyond what is possible with so-called “mini brains”, human brain organoids grown from stem cells. They further tested their 3D printing system by producing tissues from two distinct regions of the brain.

“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 were still able to talk to each other in a very special and specific way,” explained Zhang. 

The team hopes that their technique will be accessible to lots of other labs as it doesn’t need a lot of fancy equipment, but they’re also working on refinements for more specialized applications. 

“In the past, we have often looked at one thing at a time, which means we often miss some critical components,” Zhang said. “Our brain operates in networks. We want to print brain tissue this way because cells do not operate by themselves. They talk to each other. This is how our brain works and it has to be studied all together like this to truly understand it.”

The study is published in the journal Cell Stem Cell.