Currently, the best way to study brain tissue is to grow neurons in a petri dish, but those neurons can only be grown flat. A real brain contains a complicated structure of 3-D tissue. Simply giving the neurons room to grow in three dimensions didn’t prove successful: While neurons will grow into more complicated structures in the right kind of gel, they don’t survive very long or mimic the structure of a real brain.
Led by David Kaplan, the director of the Tissue Engineering Resource Center at Tufts University, researchers developed a new combination of materials to mimic the gray and white matter of the brain. The new model relies on a doughnut-shaped, spongy scaffold made of silk proteins with a collagen-based gel at the center.
The outer scaffold layer, which is filled with rat neurons, acts as the grey matter of the brain. As the neurons grew networks throughout the scaffold, they sent branches out across the gel-filled center to connect with neurons on the other side. And that configuration is about as brain-like as lab-grown tissue can get. The basic structure can be reconfigured, too.
By creating a model with six concentric rings, each populated with different types of neurons, the researchers were able to mimic the six layers of a human brain cortex. “It’s a form-fitting, Lego-like system, so we don’t have to worry about using glues, and how they might complicate the interfaces between these different compartments,” Kaplan said.
In the PNAS paper, Kaplan and his colleagues report that the tissue can already survive for months at a time in the lab. They've used it to study the effect of traumatic brain injury on neuron activity (by dropping weights onto the tissue) immediately, instead of having to dissect a brain.
“This is a very tunable way to construct a brain-like tissue with both the structure and function of a brain,” Kaplan said. And the Lego-block nature of the design means that researchers can manipulate it into the kinds of brain structures they want to study. “It could help us answer questions about neurological diseases like Alzheimer’s,” Kaplan said. And the model could be used to study the effects of the drugs used to treat brain-related ailments, like depression and epilepsy. Often, Kaplan said, the actual mechanisms of these vital drugs are a mystery.
But a good model of the brain could probe into deeper questions, too. “There are questions we have that are more difficult to define, like how we store memories or how the brain feels pain,” Kaplan said. “It’s a long list of questions to answer, which is why we're so excited.”