Scientists have 3D bioprinted functioning human brain tissue

A new method for assembling neuron cultures horizontally instead of vertically helps solve for a longstanding issue.
Illustration of 3D printed brain tissue culture with 25nm scale
The new brain tissue culture production offers more precise customization for researchers. Yan et al. / UW-Madison

Scientists have created brain “organoids” for years, but there are limitations to the tiny, lab-grown cultures. One of the most frustrating issues is a lack of control over their design, which often limits an organoid’s functionality and use. Although researchers long suspected 3D-printing could offer a solution, the workaround has so far proven difficult and ineffective. A new production breakthrough, however, could solve the longstanding barrier, and one day offer new ways of exploring treatment for diseases such as Parkinson’s and Alzeheimer’s.

As detailed in the new issue of the journal Cell Stem Cell, University of Wisconsin-Madison researchers have developed a novel 3D-printing approach for creating cultures that grow and operate similar to brain tissue. While traditional 3D-printing involves layering “bio-ink” vertically like a cake, the team instead tasked their machine to print horizontally, as if playing dominoes.

Related: A ‘brain organoid’ biochip displayed serious voice recognition and math skills.]

As New Atlas explains, researchers placed neurons grown from pluripotent stem cells (those capable of becoming multiple different cell types) within a new bio-ink gel made with fibrinogen and thrombin, biomaterials involved in blood clotting. Adding other hydrogels then helped loosen the bio-ink to solve for the 3 encountered during previous 3D-printed tissue experiments.

According to Su-Chun Zhang, a research lead and UW-Madison professor of neuroscience and neurology, the resultant tissue is resilient enough to maintain its structure, but also sufficiently malleable to permit adequate levels of oxygen and nutrient intake for the neurons. 

“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 explains in a recent university profile.

Because of their horizontal construction, the new tissue cells formed connections not only within each layer, but across them, as well—much like human neurons. The new structures could interact thanks to producing neurotransmitters, and even created support cell networks within the 3D-printed tissue.

In these experiments, the team printed both cerebral cortex and striatum cultures. Although responsible for very different functions—the former associated with thought, language, and voluntary movement; the latter tied to visual information—the two 3D-printed tissues could still communicate, “in a very special and specific way,” Zhang said.

Researchers believe their technique isn’t limited to creating just those two types of cultures, but hypothetically “pretty much any type of neurons [sic] at any time,” according to Zhang. This means the 3D-printing method could eventually help study how healthy portions of the brain interact with parts affected by Alzheimers, examining cell signal pathways in Downs syndrome, as well as use tissue to test new drugs.

“Our brain operates in networks,” Zhang explained. “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.”