Researchers have designed a realistic 3D brain-like tissue that mimics the major structural and mechanical features of the brain. It can even support the growth of functional neurons, according to the study published in the Proceedings of the National Academy of Sciences this week.
It certainly doesn’t look like a realistic brain; the model has already been described as a jelly donut, spongy rings of goo, a bullseye, and a rainbow nipple, although it looks like a slice of layered cake roll to me. But as the most sophisticated 3D model of brain tissue yet, the work could be used to study normal central nervous system function as well as disorders in complex detail.
Rather than reconstruct a whole-brain network, a Tufts University team led by David Kaplan created a modular design that replicated the fundamental features that are most relevant to the brain's functions at the tissue level. It has two key elements. First, they designed stiff, porous scaffolds made of a silk protein called fibroin. Then they filled the scaffolds with cortical neurons derived from rats, along with soft collagen gels to provide structural and biochemical support to the brain cells.
The colorful, circular modules of silk were punched into doughnuts, then assembled into concentric rings (pictured above) to simulate the six layers of human cortical brain tissue. Each layer was seeded with neurons independently, without adhesives or glue, and then immersed in the collagen gel matrix.
The soft matrix allowed axons (projections sent out by neurons) to penetrate through pores and connect to each other three dimensionally -- forming networks in the gels that resemble the complex circuitry of the brain. In the image on the right, you can see how the neurons (yellow) attached to the silk-based scaffold (blue) and formed networks throughout the scaffold pores (dark areas).
"There are few good options for studying the physiology of the living brain, yet this is perhaps one of the biggest areas of unmet clinical need when you consider the need for new options to understand and treat a wide range of neurological disorders associated with the brain,” Kaplan says in a news release.
In the brain, grey matter is made up of neuron cell bodies, while white matter is made up of bundles of axons. Because brain injuries and diseases often affect these areas differently, models are needed that compartmentalize the two. With the new model, rat neurons can attach to the scaffold (donut ring, pictured) and also send axons (labeled with green fluorescence) through the collagen gel-filled center.
The tissue stayed viable for more than two months, longer than cultures made of collagen or gel alone. Furthermore, neurons in the 3D brain-like tissue exhibited realistic electrophysiological responses to drugs and to damage caused by the impact of a falling weight -- resembling how cells in animal models respond to traumatic brain injury. The team is working on making their tissue model even more brain-like.
Images: Tufts University (top, middle) & National Institutes of Health release (bottom)