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Thursday, April 10, 2008

Self-assembling Nanofibers Heal Spinal Cords

Nano fix: An electron-microscope image shows the matrix of cylindrical nanofibers that self-assemble from engineered biological molecules in a solution.
Credit: Journal of Neuroscience

An engineered material that can be injected into damaged spinal cords could help prevent scars and encourage damaged nerve fibers to grow. The liquid material, developed by Northwestern University materials science professor Samuel Stupp, contains molecules that self-assemble into nanofibers, which act as a scaffold on which nerve fibers grow.

Stupp and his colleagues described in a recent paper in the Journal of Neuroscience that treatment with the material restores function to the hind legs of paralyzed mice. Previously, researchers have restored function in the paralyzed hind legs of mice, but those experiments involved surgically implanting various types of material, while the new substance can simply be injected into the animals. The nanofibers break down into nutrients in three to eight weeks, says Stupp.

Right now, there is no cure for the thousands of people who have injuries to the spinal cord, the bundle of long nerve fibers that connect the brain to the limbs and organs of the body. When it is damaged, nerve stem cells form a scar at the point of the injury, which blocks nerve fibers and keeps them from growing, says John Kessler, professor of stem cell biology at Northwestern's Feinberg School of Medicine, who collaborated on the work with Stupp. Nerves can no longer carry signals to and from the brain, causing patients to lose sensation, digestion, and movement. "It is like cutting a telephone cable," Kessler says. "We're thinking of regrowing the nerve fibers and rewiring the cut."

Other researchers have tried to regenerate nerve fibers using various approaches. They have used natural materials such as collagen as well as synthetic biodegradable polymers to make scaffolds that support nerves, helping them to grow. Implanting these materials at the injury requires surgery.

The new material is different because the researchers can inject it as a liquid directly into the spinal cord. Negatively charged molecules in the liquid start clumping together when they come in contact with positively charged particles such as calcium and sodium ions in the body. The molecules self-assemble into hollow, cylindrical nanofibers, which form a scaffold that can trap cells. On the surface of the nanofibers are biological molecules that inhibit scars and encourage nerve fibers to grow. "The idea of using self-assembling nanofibers that can be directly injected into the spinal cord is appealing," says Harvard Medical School professor Yang Teng, who does neural stem cell research for spinal cord injuries.

Nanofibers help nerves: Northwestern University researchers have designed molecules made of biological parts, such as amino acids and fats, that self-assemble into cylindrical nanofibers. The researchers inject a solution of the molecules into the injured spinal cords of mice, where the nanofibers promote the growth of nerve fibers.
Credit: Samuel Stupp, Northwestern University

Stupp and his colleagues have found other uses for the self-assembling molecules in the past. They have designed molecules with slightly different chemistries that promote the growth of blood vessels and that align themselves to mimic bone structure. In a 2004 Science paper, the researchers reported that in a lab culture of brain cells, versions of the material encourage the cells to grow the nerve fibers that extend into the spinal cord. They also found that the material prevents cultured nerve stem cells from growing into scar tissue.

The new work is the first test for the material to heal spinal cord injuries in animals. And Kessler says that it worked better than the researchers expected. The researchers stimulated a spinal cord injury in mice and injected the material 24 hours later. They found that the material reduced the size of scars and stimulated the growth of the nerve fibers through the scars. It promoted the growth of both types of nerve fibers that make up the spinal cord: motor fibers that carry signals from the brain to the limbs, and sensory fibers that carry sense signals to the brain. What is more, the material encouraged the nerve stem cells to mature into cells that create myelin--an insulating layer around nerve fibers that helps them to conduct signals more effectively.

Nine weeks after the injections, the mice that had been treated showed improvements over untreated mice. The animals could support their body weight on their hind legs and lift their lower bodies. "Animals that couldn't use hind legs at all now had improved ability to use their hind legs," Kessler says. "It was certainly not a cure but quite a substantial improvement in function. They're able to navigate around their cages."

Stupp has cofounded a Stokie, IL-based company called Nanotope, which is working on developing the self-assembling nanofiber therapy for human beings. The first step would be making a material that meets Food and Drug Administration standards and then testing it in clinical trials. So far, Kessler says, some basic tests of the material on human cell cultures have so far shown no apparent toxic effects.

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