ARLINGTON, Va., June 7, 2004 – Biomedical engineers at the University of Toronto have shown that they can grow new nerve cells in a block of 3-D hydrogel scaffold, a very early step toward repairing spinal cord and other nerve injuries.

About 250,000 people in the United States have a spinal cord injury, and about 10,000 new injuries occur each year. Once damaged, nerves cells in the spine and other parts of the body usually do not grow back. The Toronto researchers hope that their hydrogel scaffolds can coax nerve cells to grow and extend their axons.

“We're very interested in guiding where axons grow because they are what make the connection from the nerve, for example, to the muscle,” said Molly Shoichet, Ph.D., associate professor in Toronto 's Institute of Biomaterials and Biomedical Engineering. An article by Shoichet and co-author Ying Luo, Ph.D., appeared in the April Nature Materials.

Hydrogels are made up mostly of water but have the physical properties of a solid, like Jell-O or soft contact lenses. The researchers chose hydrogel as a scaffold material because the substance is soft and closely matches the mechanical properties of soft nerve tissue. Because they are mostly water, biodegradable hydrogel scaffolds would be readily absorbed by the body.

In a two-step process, the Toronto researchers used lasers to create about a dozen hair-thin biochemical channels in an agarose hydrogel block small enough to sit on the head of a pin. Before forming the block, the agarose solution was modified with a protected thiol. The laser's energy released the protecting group, leaving free thiol at precise points within the clear hydrogel block to react with biomolecules and form the biochemical channels.

In the second step, the researchers modified the chemical channels with a protein peptide, GRGDS, that reacted only with the newly released thiol. GRGDS adheres to nerve cells, unlike the hydrogel. After three days, nerve cells seeded on the surface of the hydrogel block had grouped near the channel openings and extended their axons into them.

Similar research has been done on two-dimensional structures, and, up to now, most three-dimensional structures have been built by layering the two dimensional ones. “What's so cool about this project,” explained Shoichet, “is that by using photochemistry and laser technology we could do patterning in three dimensions to make some simple designs.”

The researchers hope to create “more interesting patterns and more complex patterns to see how that affects cell behavior,” said Shoichet. They also hope to begin testing the hydrogel scaffolds in animals to see if there are any therapeutic effects on nerve injuries, including those in the spinal cord.

“This could have wider applications in tissue engineering because the project relates to guiding where cells are going to grow and that's important for nearly every tissue engineering application,” Shoichet said.

The project builds on a Whitaker Research Grant in 1998 that supported Shoichet's work in forming the hydrogel nerve guidance channels.

Molly Shoichet, University of Toronto
Mark Bowman, The Whitaker Foundation