First model of fully synthetic brain tissue designed by scientists

For the first time, scientists have grown functional brain-like tissues without using animal-derived materials or added biological coatings. This development opens the door to more controlled and humane neurological screening tests.

The overall goal of neural tissue engineering is to create something that closely resembles the structure and function of the human brain, enabling studies of neurological diseases and more reproducible drug testing.

“One of the drawbacks of most brain tissue platforms is that they use biological coatings to help living cells grow. These animal-derived coatings are poorly defined, making it difficult to recreate their exact composition for reliable testing,” said Iman Noshadi, an associate professor of bioengineering at UCR who led the team.

Additionally, using animal brains to conduct research relevant to human conditions – as is currently the norm – is not ideal. There are significant genetic and physiological differences between rodent and human brains.

This platform could reduce, and in some cases eliminate, the need to use animal brains for this purpose and aligns with the US FDA’s efforts to phase out requirements for animal testing in drug development.

How the new brain-like scaffolding works

The new hardware, described in the Advanced functional materials journal, functions as a scaffold on which to grow donor brain cells and could be used to model head injuries, strokes or neurological diseases like Alzheimer’s.

It is primarily composed of a common polymer known for its chemical neutrality called polyethylene glycol, or PEG. Typically, living cells do not attach to PEG without the addition of proteins like laminin or fibrin.

By remodeling PEG into a maze of textured, interconnected pores, the research team transformed an inert material into a matrix that cells recognize, colonize, and use to build functional neural networks. Once these cells mature, they could exhibit donor-specific neuronal activity, allowing direct evaluation of drugs targeted to their neurological conditions.

“As the technical scaffolding is stable, it allows for longer-term studies,” said Prince David Okoro, lead author of the study and a doctoral student in Noshadi’s lab. “This is particularly important because mature brain cells better reflect actual tissue function when studying relevant diseases or trauma.”

Innovative manufacturing and future applications

To build the scaffold structure, the team used a process involving water, ethanol and PEG flowing through interlocking glass capillaries. When the mixture reaches an external water stream, its components begin to separate. A flash of light stabilized this separation, locking the porous structure.

The pores allow oxygen and nutrients to flow efficiently throughout the structure, essentially nourishing the donated stem cells.

“The material ensures that cells get what they need to grow, organize and communicate with each other in brain-like groups,” Noshadi said. “As structure more closely mimics biology, we can begin to design tissue models with much finer control over cell behavior.”

The research began in 2020. Currently, the scaffolding material is only about two millimeters wide. Moving forward, the team is working on scaling the model and has submitted a related paper focused on liver tissue.

The group’s long-term goal is to develop a suite of interconnected organ-level cultures that reflect how the body’s systems interact. They hope that these tissue platforms will provide stability, longevity and functionality comparable to the brain tissue model.

“An interconnected system would allow us to see how different tissues respond to the same treatment and how a problem in one organ can influence another. This is a step toward a more integrated understanding of human biology and disease,” Noshadi said.