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3D-printed human brain tissue could advance Alzheimer’s research

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A team of US researcher has developed the first 3D-printed brain tissue that can grow and function like typical brain tissue.

The achievement, by University of Wisconsin–Madison researchers, as important implications for scientists studying the brain and working on treatments for a broad range of neurological and neurodevelopmental disorders, such as Alzheimer’s and Parkinson’s disease.

Su-Chun Zhang is professor of neuroscience and neurology at UW–Madison’s Waisman Center.

The researcher said: “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.”

Printing methods have limited the success of previous attempts to print brain tissue, according to Zhang and Yuanwei Yan, a researchers in Zhang’s lab.

Instead of using the traditional 3D-printing approach, stacking layers vertically, the scientists went horizontally.

The researchers situated brain cells, neurons grown from induced pluripotent stem cells, in a softer “bio-ink” gel than previous attempts had employed.

Zhang said:“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.”

The cells are laid next to one another like pencils laid next to each other on a tabletop.

Yan said: “Our tissue stays relatively thin and this makes it easy for the neurons to get enough oxygen and enough nutrients from the growth media.”

The results speak for themselves — or rather, the cells can speak to each other.

The printed cells reach through the medium to form connections inside each printed layer as well as across layers, forming networks comparable to human brains.

The neurons communicate, send signals, interact with each other via neurotransmitters, and even form proper networks with support cells that were added to the printed tissue.

Zhang said: “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 offers precision not found in brain organoids, miniature organs used to study brains.

The organoids grow with less organisation and control.

Zhang said: “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.

“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.”

That specificity provides the researchers with flexibility.

The printed brain tissue could be used to study signaling between cells in Down syndrome, interactions between healthy tissue and neighbouring tissue affected by Alzheimer’s, testing new drug candidates, or even watching the brain grow.

Zhang said: “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 accessible to many labs because it does not require special bio-printing equipment or culturing methods to keep the tissue healthy, and can be studied in depth with microscopes, standard imaging techniques and electrodes already common in the field.

The researcher team would like to explore the potential of specialization, though, further improving their bio-ink and refining their equipment to allow for specific orientations of cells within their printed tissue.

Yan said: “Right now, our printer is a benchtop commercialized one.

“We can make some specialised improvements to help us print specific types of brain tissue on-demand.”

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