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Tufts University Circle around: Six concentric rings (dyed with food coloring) of silk sponge mimic the six layers of the brain’s cortex.
Bioengineers have built a donut-shaped scaffold that supports the growth of brain-like tissue, they reported 11 August in the Proceedings of the National Academy of Sciences1.
The tissue stayed alive on the scaffold — made of silk with a dollop of collagen gel — for nine weeks. The typical lifespan of brain tissue in other three-dimensional (3D) gel-based environments is one week.
Lab-grown brain tissue is in high demand because researchers face a paucity of postmortem human brains for research. Tissue that mimics the brain is particularly difficult to grow in the lab because it has a complex architecture and many types of specialized cells. Although neurons can be cultured with relative ease, certain types of neurons in the brain are arranged in specific layers and are supported and protected by non-neuronal cells.
Researchers have thus far cultured neurons in 3D gel matrices or have coaxed neuronal stem cells into becoming clumps of tissue that resemble ‘mini-brains.’ However, in these systems, neurons grow axons — the long, thin projections that connect neurons — in a disorganized tangle, rather than being oriented together into tracts that connect distant regions.
The new system successfully mimicked this organization using two sets of biomaterials. The first features six concentric rings of silk protein sponge that provide a structure for neurons to attach to. This imitates the six layers found in the outer folds of the brain, or the cortex. The researchers seeded each ring with different populations of neurons.
The researchers also filled the silk sponge’s pores and the very center of the compound ring structure with a collagen gel matrix. As the neurons grew, they extended their axons across the center space and connected to other neurons, just as they do in the brain.
By varying the size of the center hole and the stiffness of the silk scaffold, the researchers were able to create a system with the elasticity of rodent brains.
They also found that the system shows a spike in electrical activity after blunt injury, similar to the activity seen in animal models2.
The six-layer donut shape is just one possible structure, the researchers say, and they can cut the silk scaffold to mimic the structure of different brain regions. They can also add other types of cells, such as astrocytes, oligodendrocytes and glia, to more closely resemble the cell types in a functional brain.
References:
1. Tang-Schomer M.D. et al. Proc. Natl. Acad. Sci. USA Epub ahead of print (2014) PubMed
2. Hunt R.F. et al. Front. Cell Neurosci. 7, 89 (2013) PubMed
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