Brown scientists created patterns in silicone to guide the growth of nerves: regular (top left) and a more natural pattern (bottom left). The resulting nerve growth (red) was much straighter and directed with the regular pattern than the natural. Credit: Cristina Lopez-Fagundo and Diane Hoffman-Kim/Brown University
Growing nerves to correct all kinds of neurological disorders and injuries is a major goal of medicine, something that can revolutionize neurosurgery similarly to how bypasses and stents changed vascular therapy. One major challenge to growing nerves is guiding them to develop in a straight line or any shape that’s required. It’s already been known that Schwann cells, or neurolemmocytes, play a role in guiding the growth patterns of nerves, and researchers at Brown University seem to have figured out how to manipulate them to drive nerve growth.
The team used specially created poly(dimethylsiloxane) materials to create an environment within which Schwann cells can act as guideposts for nerve growth.
Some details from Brown:
“We were able to deconstruct the topography of Schwann cells,” said [graduate student Cristina] Lopez-Fagundo. “We were then able to manipulate it into different designs to better understand the influence this topography has.”
They came up with six archetypal designs. One of them mimicked the somewhat messy real-world layout of Schwann cells but the other five were arranged in neat horizontal rows. In one the elliptical Schwann cell bodies were few and far between. In another they were densely packed and in another their spacing was the exact average of Lopez-Fagundo’s measurements. Another design had no “processes” to connect the ellipses and another had only processes but no ellipses.
Using Brown’s microfabrication facility, Lopez-Fagundo patterned their designs on silicon wafers (like those used to make computer chips) and then transferred them to silicone squares about a centimeter on a side so that the ellipses and processes were in raised relief on the silicone. Then they put each pattern in a cell culture of rat neurons and watched them as the neurons grew across each pattern of artificial Schwann cells. As a control for their experiment, they also cultured cells on unpatterned silicone squares.
All of the patterns encouraged some directed neuron growth compared to the random growth of neurons on the unpatterned squares, but clearly some patterns did better than others.
After 17 hours, the two best patterns were the ones with only processes and the one with average ellipse spacing. The natural replica pattern and the one with only ellipses fared the worst.
But by day five, new winners emerged: the patterns where the ellipses were farther than average and nearer than average. Hoffman-Kim said she was surprised that the nerve cells didn’t remain content to follow the straightforward pattern of plain horizontal tracks formed by the process-only pattern. Meanwhile, to some extent, the neurons grew the proper way even without a continuous track at all, for instance in the ellipse-only pattern.
Study in Acta Biomaterialia: Navigating neurites utilize cellular topography of Schwann cell somas and processes for optimal guidance