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http://www.technologyreview.com/Nanotech/20534/

Wednesday, April 09, 2008

Nanofibers Heal Spinal Cords

Injected directly into the spinal cords of paralyzed mice, a new

material restores use of the animals' hind legs.

By Prachi Patel-Predd

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 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

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.

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.

Copyright Technology Review 2008.

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