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Biological Chemistry

Bendy Neuronal Arrays Could Boost Cellular Engineering

Tissue Engineering: Flexible sheets of neurons may improve studies of single cells and platforms for testing drugs

by Jyoti Madhusoodanan
May 12, 2015

Researchers in Japan have grown sturdy, flexible grids of cultured nerve cells on a patterned hydrogel film. This neuronal array can be rolled up, laminated, or squeezed with tweezers without harming the neurons’ biological functions (ACS Biomater. Sci. Eng. 2015, DOI: 10.1021/acsbiomaterials.5b00020). When connected to electrodes or grown with other cell types, the arrays could help scientists study cell functions or test drugs more effectively, the researchers say.

Neurons are usually grown in plastic or glass dishes in the lab, but they grow better on soft, gel-like surfaces. Matsuhiko Nishizawa of Tohoku University, in Japan, and his colleagues had previously designed flexible films by first growing a pattern of skeletal muscle cells in a dish and then transferring them to a soft collagen sheet. However, moving nerve cells in this way damaged them. So the researchers looked for ways to grow the cells on the flexible surface. They took dried collagen films, printed a microsized grid pattern on them with a commercial cellular growth substance, and then poured a suspension of nerve cells over the films.

CULTURED CONNECTIONS
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Credit: ACS Biomater. Sci. Eng.
Pouring a suspension of neurons over a micropatterned collagen film forms a cellular array (left). The resulting flexible film (right) can be moved without disturbing the neurons’ function.
Illustration and photo of flexible neural array in a hydrogel.
Credit: ACS Biomater. Sci. Eng.
Pouring a suspension of neurons over a micropatterned collagen film forms a cellular array (left). The resulting flexible film (right) can be moved without disturbing the neurons’ function.

Within 15 hours, the neurons had arranged themselves at the nodes of the grid and sent out fingerlike extensions to connect to other cells. When the researchers treated the cells in the film with a chemical stimulant, bradykinin, or stimulated them with a microelectrode chip, the concentration of calcium ions in the cells increased, suggesting that the cells were physiologically active. The team also activated specific sections of the grid using microelectrodes to study how nerve signals rippled through nearby cells.

Nishizawa says these flexible neuronal arrays could improve studies of single cells and tests of new drug therapies. For example, neurons on such sheets could be placed next to arrays of muscle cells to see how a drug affects each kind of cell at a neuromuscular junction. In the future, he says such neuronal arrays could lead to device implants to treat neurodegenerative conditions.

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