The brain is one of the most important tissues in the body, but it's very difficult to study in living humans. While brains made in a laboratory may be reminiscent of horror movie villains, researchers at Tufts University have bioengineered a functional brain-like gel model that for the first time mimics the responses of actual living brains. A functional 3D brain tissue model brings researchers one step closer to understanding what's going on up in our gray matter.
In a study published today in Proceedings of the National Academy of Sciences (PNAS), researchers from Tufts report that their brain model reacts in similar ways to electrical and chemical stimulation as a living human brain. The 3D brain can also last for several months, a much longer shelf life than past models.
The model is made of extracellular matrix (ECM) gels, silk scaffolding, and brain cells called neurons. While the design is basic, it provides a solid blueprint for more complex brain function.
“Based on the architecture and functions of the brain, we tried to emulate or mimic these features in the biomaterial designs, cells, and system,” said the study’s senior author David Kaplan, a professor and chair of Tufts’ biomedical engineering department, in an email to Healthline.
It's Alive — Sort of
To develop the model, researchers examined many different types of gels and sponges, in combination and alone. “We examined gels alone, sponges alone, and variants of each of these, as well as the combination system that we found worked best,” Kaplan said.
For these researchers, fabricating human tissue isn’t a new process. “This all emulated from our longstanding studies on biomaterial designs to capture the required structure, morphology, chemistry, and mechanics to match cell and tissue culture needs in 3D,” Kaplan said.
The resulting 3D brain-like tissue is made of silk protein-based scaffolding, ECM composite, and cortical neurons — the cells that make up what is commonly known as the brain's gray matter. “For the brain system, we were not sure how well the connectivity would form and how well the functions would show, but these turned out well due to the biomaterial designs and overall system integration,” Kaplan said.
The researchers first tested the brain tissue's response to electrical stimulation. Then, they observed the impact of dropping a weight onto the model, simulating a traumatic brain injury (TBI). Like a real brain, the model released glutamate, a chemical known to accumulate after a TBI.
Brains of the Future
Future tests of the brain model could examine the effects of medications on the brain, as well as other types of trauma. The 3D model could also be used to explore brain dysfunction.
“We feel it has extensive potential in many areas of brain research, including studies of drugs, brain dysfunction, trauma and repair, the impact of nutrition or toxicology on disease state and functions, etc.” Kaplan said.
As with any model, this jelly brain matter could benefit from further tinkering.
“We see many directions to go with this, building on what we have done as a starting point,” Kaplan said. Modifications could include adding more complexity to better emulate brain function and extending the shelf life of the model to six months in order to study slowly developing neurological diseases like Alzheimer's.