A team of scientists at the University of Wisconsin-Madison, the official state university of Wisconsin, created the first 3D printed brain tissue capable of growing and functioning normally. It is a significant achievement for scientists researching the brain and developing treatments for a wide range of neurological and neurodevelopmental disorders, including Alzheimer’s and Parkinson’s disease.
“This could be a hugely powerful model to help us understand how brain cells and parts of the brain communicate in humans. It could change the way we look at stem cell biology, neuroscience, and the pathogenesis of many neurological and psychiatric disorders.”
– Su-Chun Zhang, professor of neuroscience and neurology at UW–Madison’s Waisman Center
World’s First 3D Printed Brain Tissue
Previous attempts to 3D print brain tissue have had limited success, according to Zhang and Yuanwei Yan, a scientist in Zhang’s lab. The team behind the new 3D-printing process published their method today in the journal Cell Stem Cell.
The researchers took a different approach to 3D printing, stacking layers horizontally rather than vertically. They placed brain cells, 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 is soft enough to allow the neurons to grow into each other and start talking to each other,” Zhang says.
The cells are laid next to each other like pencils laid next to each other on a tabletop.
“Our tissue stays relatively thin and this makes it easy for the neurons to get enough oxygen and enough nutrients from the growth media,” Yan says.
The results speak for themselves – that is, the cells can communicate with one another. The printed cells penetrate the medium to form connections within each printed layer as well as across layers, resulting in networks similar to human brains. Neurons communicate, send signals, interact with one another via neurotransmitters, and even form proper networks when support cells are added to the printed tissue.
Zhang continued, “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.”
The printing technique provides precision – control over the types and arrangements of cells – which brain organoids, miniature organs used to study the brain, lack. The organoids grow with little organisation and control.
“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.”
– Su-Chun Zhang, MD, PhD
Zhang added, “Because we can print the tissue by design, we can have a defined system to look at how our human brain network operates. We can look very specifically at how the nerve cells talk to each other under certain conditions because we can print exactly what we want.”
This specificity provides flexibility. The printed brain tissue could be used to study cell signalling in Down syndrome, interactions between healthy tissue and Alzheimer’s-affected tissue, drug testing, and even brain growth.
Zhang concluded, “In the past, we have often looked at one thing at a time, which means we often miss some critical components. 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. 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 look at the molecular mechanisms underlying brain development, human development, developmental disabilities, neurodegenerative disorders, and more.”
The new printing technique should also be available to a wide range of laboratories. It does not require special bio-printing equipment or culturing methods to keep the tissue healthy, and it can be studied in depth using microscopes, standard imaging techniques, and electrodes that are already widely used in the field.
The researchers would like to investigate the potential of specialisation, however, by improving their bio-ink and refining their equipment to allow for specific cell orientations within the printed tissue.
Yuanwei Yan said, “Right now, our printer is a benchtop commercialised one. We can make some specialised improvements to help us print specific types of brain tissue on-demand.”
This study was supported in part by NIH-NINDS (NS096282, NS076352, NS086604), NICHD (HD106197, HD090256), the National Medical Research Council of Singapore (MOH-000212, MOH-000207), Ministry of Education of Singapore (MOE2018-T2-2-103), Aligning Science Across Parkinson’s (ASAP-000301), the Bleser Family Foundation, and the Busta Foundation.
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