With the aim of gaining improved understanding of how the brain and these networks work, researchers at the University of Illinois at Urbana-Champaign used stem cells to engineer living bio-hybrid nerve tissue to develop 3-D models of neural networks.

First author Gelson Pagan-Diaz compares the resulting tissue to a computer processing unit, which provided the basic principle to today’s supercomputer.

“Being able to form 3-dimensional tissue consisting of neurons can give us the ability to develop tissue models for drug screening or processing units for biological computers,"

Pagan-Diaz said. Pagan-Diaz is a graduate student in Prof. Rashid Bashir’s group in the Department of Bioengineering at the Grainger College of Engineering. Bashir is also the Dean of the College.

Biofabricated Neural Constructs

The brain is challenging to study in an actual person, but being able to understand how these networks develop using a 3-D model outside the body promises to give researchers a new tool to better understand how it works. These models will be able to help understand how abnormalities form, e.g. what gives rise to diseases such as Alzheimer’s.

The team was able to give 3-D geometry to the living tissue made of neurons which optogenetics, so they could be activated with blue light. These tissues could be used to study complex behaviors that happen in the brain and how these tissues react with new drugs being developed.

[caption id=“attachment_101808” align=“aligncenter” width=“758”]Different neural tissue geometries Different neural tissue geometries formed with the new biofabrication method and imaged using confocal microscopy
Credit: University of Illinois Department of Bioengineering[/caption]

It could also mean less reliant on animals to test these drugs in the future.

“If we can control how these neurons communicate with each other, if we can train them using optogenetics, if we can program them, then we can potentially use to perform engineering functions. In the future, our hope is that by being able to design these neural tissue, we can begin to realize biological processing units and biological computers, similar to the brain,"

Bashir said.

Brain Morphology Mimicry

The team developed neural tissue mimics that can form different shapes. The team used hydrogels and fibrin to make millimeter to centimeter scale structures that doesn’t have rigid scaffolds and can be molded into a number of desired shapes.

“It’s a bundle of hundreds to thousands of microns of cells that contains a lot of populations with a genetic makeup similar to in vivo tissues,” Pagan-Diaz explained. “As we continue develop these bio-fabrication methods, we should be able to capture a lot of the phenomena that happens in vivo. Once we can prove that, we will be able to mimic the morphology that we see in the brain. Once we show that the tissue engineered outside the body is similar to the tissue in the body, then we can then fabricate them over and over again."

Besides drug testing, the team is especially interested in being able to recapitulate the way these networks might develop learning and memory.

“Being able to fabricate these tissue mimics outside the body allows us to characterize and study their electrical activity in great detail, the broad set of design rules due to the 3-D structure and shapes gives you a lot more experimental freedom and open up new avenues of research in neuroscience, medicine, and engineering applications,"

Pagan-Diaz said.

[1] Gelson J. Pagan-Diaz, Karla P. Ramos-Cruz, Richard Sam, View ORCID ProfileMikhail E. Kandel, Onur Aydin, M. Taher A. Saif, Gabriel Popescu, and Rashid Bashir. Engineering geometrical 3-dimensional untethered in vitro neural tissue mimic. Proceedings of the National Academy of Sciences Dec 2019, 201916138; DOI:10.1073/pnas.1916138116

Top Image: a ring-shaped neural tissue mimic was installed onto a cylindrical glass rod, and the image shows how dense neural extensions are able to form on this substrate due to the geometrical advantage of the tissue. Credit: University of Illinois at Urbana-Champaign Department of Bioengineering

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