Nanostructure may be key to regeneration

A tiny new scaffold that assembles itself inside the body could point the way to regeneration of spinal cords and the ability to grow tissues ranging from bone cartilage to blood vessels, scientists say.

"This is a magic material," said one of the scaffold's inventors, Northwestern University chemistry professor Samuel Stupp, who reported the discovery last week in Science magazine.


Other researchers were almost as effusive. "This work is excellent. It is very beautiful," said Massachusetts Institute of Technology molecular biologist Shuguang Zhang, who is developing a similar device.

"It's a really novel approach," said MIT bioengineering professor Robert Langer, a pioneer in the field of miniature biomedical technology.


The invention is the latest development in the burgeoning field of nanotechnology, which combines chemistry, engineering and biology to create extremely small devices for use by industry, medicine and the military.

Stupp's scaffold, for example, is made up of cylindrical fibers, each with a diameter of 7 nanometers - less than 1/10,000th of the thickness of a human hair.

Because such nanomachines are too small to be manipulated by hand, researchers try to get them to organize themselves, relying on chemical affinities and electrical charges to produce specific molecular configurations.

'Real application'

For more than a decade, researchers have been creating self-assembling nanostructures to show the feasibility of the process. But few, if any, of these inventions have had a practical function, until now.

"This has a real application," said Tejal Desai, a biomedical nano researcher at Boston University.

The inventors also are the first to announce the creation of a device that can assemble itself inside a living organism, which would eventually allow doctors to use such structures in the human body.

To the naked eye, the scaffold, which consists of a combination of amino acids and fatty acids, is a blob. "It looks like a piece of transparent Jell-O from the refrigerator," Stupp said.


Under a microscope, it resembles a loosely woven fabric made of cylindrical nanofibers.

Scientists deliver the device by injecting a pure water solution containing the disassembled scaffold molecules. Before injection, these molecules float freely. When they come into contact with fluid from a living organism, they arrange themselves into the cylindrical nanofibers that form the scaffold.

The transformation is triggered by calcium and sodium ions. "Any physiological fluid of any living thing will elicit this response," said Stupp.

Making connections

The scaffold incorporates a natural molecule called IKVAV, which encourages neurons to sprout new connections to other nerve cells. IKVAV is present in living organisms, but it normally is so diluted that it has little effect. The scaffold amplifies the signal a thousand-fold.

In tests, the IKVAV scaffold produced a "surprising" number of new nerve connections, said Gabriel Silva, one of the paper's lead authors. Recent experiments on the retinal nerves of rats have yielded more promising results.


The scaffold not only keeps neurons in constant contact with IKVAV, but also provides physical support to help nerve cells grow. Researchers are finding that many types of cells grow more robustly in a three-dimensional environment than in a two-dimensional setting, such as a flat petri dish.

Scientists hope to use the structures to help reverse paralysis from spinal cord damage.

'Complete surprise'

Researchers also discovered that the scaffold somehow stops damaged neurons from making scar tissue, which clogs up the site of many injuries and obstructs nerve regeneration.

"It was a complete surprise," said Stupp. Researchers aren't sure why it happens.

Stupp envisions starting human clinical trials of the scaffold within five years. His colleague Silva, now an assistant bioengineering professor at the University of California, San Diego, was more conservative, predicting that trials would not happen for 10 years.


Other spinal cord researchers have experimented for years with larger, pre-constructed scaffolds. Those devices, several millimeters long, have produced partial recovery of movement in injured rats and mice.

But the larger scaffolds must be surgically implanted in the spinal cord, a delicate and risky procedure. The nanoscaffolds could be administered with an injection, researchers said, and are biodegradable, which means theoretically they would disappear over time.

Scientists concede that there are many kinks to be worked out. For example, they don't know how to orient the scaffolding so that damaged nerves regrow in the right direction.

'Little gold mine'

Even so, scientists believe nanoscaffolds have enormous potential. "The implications of this go beyond nerves," said Langer, who helped develop tiny structures to foster growth of skin grafts - a technology now used on human patients.

Langer is developing prefabricated nanostructures and is experimenting with 20 different tissues. By adding various bioactive substances to the scaffold structure, researchers think they can elicit growth in a wide range of cells.


"It's a little gold mine, this thing," Stupp said.

In addition to working on neural nanoscaffolds, Stupp is developing structures to stimulate growth of cartilage, bone, pancreas and blood vessels.

Zhang, the MIT researcher, is working on nerve, cartilage, liver and heart cells. Silva is studying whether the scaffold can be used to transplant cells into damaged retinas.

Perhaps most intriguing, Stupp, Zhang and others are trying to use scaffolds to prompt stem cells to develop into specialized tissues.

"It's exciting. Nobody has been here before," said Zhang said of nanoscaffolding. "Everything we do is new."