Sea worms, jellyfish, geckos and spiders may seem unlikely muses to cutting-edge technology. But these creatures are helping stimulate medical innovations — including new adhesives, diagnostic tests and needles — that are slowly migrating from the lab to the clinic.
“Evolution is the best problem-solver,” said Jeffrey Karp, co-director of the Center for Regenerative Therapeutics at Brigham and Women’s Hospital in Boston. “Often in technology, we encounter barriers that appear to be insurmountable,” he said, but sometimes answers can be found in the most obvious place: nature itself.
Karp is a leader in the burgeoning fields of bio-inspired and biomimetic medicine, in which medical devices are inspired by or imitate nature. Five years ago, he and colleagues at MIT developed a waterproof glue based on the sticky properties of geckos’ feet. The adhesive, which might be used by surgeons to seal holes in organs and other tissue, is being tested in large animals, a step that would be followed by human trials.
In October, Karp and Bob Langer at MIT published a paper on a three-layer quick-release adhesive they are developing to protect the fragile skin of babies. Each year, 1.5 million U.S. newborns are injured because of rips and tears from tapes that hold intravenous tubes and other devices onto the skin. The elderly, too, often suffer painful abrasions from medical tape.
Karp said his team found inspiration in multilayered minerals such as mica, which form strong bonds in one direction but pull apart easily in others, and spider webs, which have sticky parts that grab prey and non-sticky parts that allow the spider to walk on them. These properties help make the glue gentle and strong at the same time. Karp says his adhesive is five to 10 times easier to remove than existing products.
To make the tape, the team developed a middle layer that has different physical properties depending on which way it’s pulled. Using a laser, the researchers etched a pattern on the in-
between layer to control how the adhesive and the backing interact. The next step is creating a prototype that will be tested in clinical trials, Karp said.
Karp and another group at MIT also came up with a microchip that uses tiny strands of DNA that grab and hold tumor cells in the bloodstream.
“We became inspired by jellyfish that have these long tentacles that extend far away from their main body,” he said. These arms expand their reach for food. “Regardless of where the food lands, they can capture it.”
The microchip can be used to count and sort cancer cells; both functions are important to determine how well chemotherapy or other treatments are working. It’s also important to know the number of cancer cells remaining after chemotherapy, so that doctors can determine how resistant the tumor is or whether another one is likely to appear elsewhere in the body.
“The key is to know which drugs the remaining cells would be most susceptible to,” Karp said. “What you really want to do is collect them and study the biology of the cells, and subject them to different kinds of chemo so you know which one is best to use.”
The microchip also counts cells 10 times faster than existing devices, giving doctors critical data more quickly, according to a study published in Proceedings of the National Academy of Sciences.
If the device works, the microchip will provide valuable information about how tumors and their treatments are progressing, according to Howard Scher, chief of medical genitourinary oncology at the Memorial Sloan-Kettering Cancer Center in New York, who was not part of Karp’s study.
“You can watch the biology of the cancer change,” he said. The device “gives you clues as to why a treatment may no longer be working.”
The scientists took short strands of DNA that bind with the targeted cancer cell surface and copied them hundreds of times. By connecting these DNA strands, they produced wispy material much longer than the cell itself. One end of the strand is connected to the microchip; the other floats free in the bloodstream. As cancer cells drift by, the strands bind to them, just as a jellyfish grabs food, Karp explained. The team is about to begin testing on patient tumor samples.
Russell Stewart, a professor of bioengineering at the University of Utah, is inspired by another marine creature: the sandcastle worm. This worm, named for its ability to assemble underwater reefs that resemble sand castles, is coveted by researchers trying to figure out how to create adhesive substances that work inside the water-heavy human body.
Ever tried putting on a plastic bandage in the shower? Common glues and tapes don’t stick to wet surfaces because the water prevents the glue from adhering. Super Glue and similar products are water-insoluble if you create the bond while the glue is dry, but they don’t adhere to wet surfaces.
Another problem in developing bio-inspired medical devices is the body’s immune system, which usually rejects foreign objects. “Our bodies are extremely good at recognizing materials that don’t belong there and attacking them,” Stewart explained.
The worm’s glue bonds, in part, by using oppositely charged proteins to form a fluid that is denser than water. The worm-inspired adhesive is a fluid that can be separated from water but still adheres to wet surfaces.
Stewart and co-workers created chemical analogs that mimic the worm’s adhesive proteins and properties.
Stewart and collaborators Ramesha Papanna and Kenneth Moise at the University of Texas Medical School in Houston are testing the new adhesives for sealing holes in fetal membranes. If it works, the glue would allow surgeons to perform advanced surgeries to treat conditions in the uterus, such as spina bifida, Stewart said.
The project is in preclinical trials and years from being used in hospitals.
Still, Stewart said, “If we could solve this problem, there are lots of other fetal surgeries that could be done in the womb.”
Researchers working in bio-
inspired engineering have benefited from better technology to dissect organisms at the atomic level, according to David J. Mooney, a research scientist at Harvard University’s Wyss Institute for Biologically Inspired Engineering.
“We are increasingly able to take apart various molecules, genes, proteins and regulatory molecules in living systems that we couldn’t 10 or 20 years ago,” Mooney said. “By mimicking aspects of the structure and chemistry, or even [doing so] at higher scales, understanding the complete organism is increasing. We can mimic function of entire organisms and not just components.”
Mooney recently published a paper showing a new design for a sponge based on the cellular structure of seaweed. The sponge can be shrunk to a fraction of its size and injected into a part of the body. There, it re-hydrates and regains its original size “just like a kitchen sponge,” Mooney said.
The sponge, built from a polymer derived from seaweed, can be used to fill space in tissue that has been removed, to signal cells around it to perform some task or to deliver drugs slowly over time.
Like other advances in science, bio-inspired devices will have their share of false starts, according to some experts.
“Now and then there will be discoveries, but I don’t see how it’s completely revolutionizing everything,” said Jeffrey Chalmers, professor of chemical and biomolecular engineering at Ohio State University. “It’s going to take a while.”
Fiorenzo Omenetto understands all too well the years of testing it takes before such inventions make it out of the lab. In September, Omenetto, a professor of biomedical engineering at Tufts University, unveiled a tiny electronic device wrapped in silk that performs its task and then decomposes in just a few weeks.
To do that, researchers dissolved and then reassembled natural silk crystals into tiny structures. These structures coated the silicon circuits and small amounts of magnesium used to conduct electricity. The silk provides the device with a structure. After a certain period, the crystal structure dissolves, and so does the silicon and magnesium inside. The amount of the material is so small that it is safely absorbed into the body — in effect, the silk functions as a biodegradable circuit.
This could become a new way of delivering drugs in precise amounts or stimulating bone healing without leaving a permanent device in the body. But the concept is still years away from a trial, according to Omenetto. As with many bio-inspired devices, the biggest hurdle is getting it to work the same way every time.
It’s easier to build a metal implant — like a hip joint — that performs the same way every time than to build an equally consistent biological device, according to Omenetto. That’s because biological components, such as silk, aren’t fabricated by machine.
The challenge, he says, is being able to repeat these results with constantly shifting biological materials. “Think about silk: It has variability depending on where you get it. You have to be as consistent as possible.”
Niiler writes about science and technology, and lives in Chevy Chase.