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TR10: Nanohealing

Tiny fibers will save lives by stopping bleeding and aiding recovery from brain injury, says Rutledge Ellis-Behnke.
March 12, 2007
Rutledge Ellis-BehnkeRutledge Ellis-Behnke
Rutledge Ellis-BehnkeAsia Kepka

In the break room near his lab in MIT’s brand-new neuroscience building, research scientist Rutledge Ellis-Behnke provides impromptu narration for a video of himself performing surgery. In the video, Ellis-Behnke makes a deep cut in the liver of a rat, intentionally slicing through a main artery­. As the liver pulses from the pressure of the rat’s beating heart, blood spills from the wound. Then Ellis­-­Behnke covers the wound with a clear liquid, and the bleeding stops almost at once. Untreated, the wound would have proved fatal, but the rat lived on.

The liquid Ellis-Behnke used is a novel material made of nanoscale protein fragments, or peptides. Its ability to stop bleeding almost instantly could be invaluable in surgery, at accident sites, or on the battlefield. Under conditions like those inside the body, the peptides self-assemble into a fibrous mesh that to the naked eye appears to be a transparent gel. Even more remarkably, the material creates an environment that may accelerate healing of damaged brain and spinal tissue.

Ellis-Behnke stumbled on the material’s capacity to stanch bleeding by chance, during experiments designed to help restore vision to brain-­damaged hamsters. And his discovery was itself made possible by earlier serendipitous events. In the early 1990s, Shuguang Zhang, now a biomedical engineer at MIT, was working in the lab of MIT biologist Alexander Rich. Zhang had been studying a repeating DNA sequence that coded for a peptide. He and a colleague inadvertently found that under certain conditions, copies of the peptide would combine into fibers. Zhang and his colleagues began to reëngineer the peptides to exhibit specific responses to electric charges and water. They ended up with a 16-amino-acid peptide that looks like a comb, with water-loving teeth projecting from a water-repelling spine. In a salty, aqueous environment–such as that inside the body–the spines spontaneously cluster together to avoid the water, forming long, thin fibers that self-assemble into curved ribbons. The process transforms a liquid peptide solution into a clear gel.

Originally, Ellis-Behnke intended to use the material to promote the healing of brain and spinal-cord injuries. In young animals, neurons are surrounded by materials that help them grow; Ellis-Behnke thought that the peptide gel could create a similar environment and prevent the formation of scar tissue, which obstructs the regrowth of severed neurons. “It’s like if you’re walking through a field of wheat, you can walk easily because the wheat moves out of the way,” he says. “If you’re walking through a briar patch, you get stuck.” In the hamster experiments, the researchers found that the gel allowed neurons in a vision-related tract of the brain to grow across a lesion and reëstablish connections with neurons on the other side, restoring the hamster’s sight.

It was during these experiments that Ellis-Behnke discovered the gel’s ability to stanch bleeding. Incisions had been made in the hamsters’ brains, but when the researchers applied the new material, all residual bleeding suddenly stopped. At first, Ellis-Behnke says, “we thought that we’d actually killed the animals. But the heart was still going.” Indeed, the rodents survived for months, apparently free of negative side effects.

The material has several advantages over current methods for stopping bleeding. It’s faster and easier than cauterization and does not damage tissue. It could protect wounds from the air and supply amino-acid building blocks to growing cells, thereby accelerating healing. Also, within a few weeks the body completely breaks the peptides down, so they need not be removed from the wound, unlike some other blood-stanching agents. The synthetic material also has a long shelf life, which could make it particularly useful in first-aid kits.

The material’s first application will probably come in the operating room. Not only would it stop the bleeding caused by surgical incisions, but it could also form a protective layer over wounds. And since the new material is transparent, surgeons should be able to apply a layer of it and then operate through it. “When you perform surgery, you are constantly suctioning and cleaning the site to be able to see it,” says Ram Chuttani, a gastroenterologist and professor at Harvard Medical School. “But if you can seal it, you can continue to perform the surgery with much clearer vision.” The hope is that surgeons will be able to operate faster, thus reducing complications. The material may also make it possible­ to perform more procedures in a minimally invasive way by allowing a surgeon to quickly stop bleeding at the end of an endoscope.

Chuttani, who was not involved with the research, cautions that the work is still “very preliminary,” with no tests yet on large animals or humans. But if such tests go well, Ellis-Behnke estimates, the material could be approved for use in humans in three to five years. “I don’t know what the impact is going to be,” he says. “But if we can stop bleeding, we can save a lot of people.” Ellis-Behnke and his colleagues are also continuing to explore the material’s nerve regeneration capabilities. They’re looking for ways to increase the rate of neuronal growth so that doctors can treat larger brain injuries, such as those that can result from stroke. But such a treatment will take at least five to ten years to reach humans, Ellis-Behnke says.

Even without regenerating nerves, the material could save countless lives in surgery or at accident sites. And already, the material’s performance is encouraging research by demonstrating how engineering nanostructures to self-assemble in the body could profoundly improve medicine.