Quick seal. Adding a glue modeled on the biochemistry of mussel attachment quickly sealed a punctured fetal membrane in rabbits, protecting the fetal bunnies inside.

Martin Ehrbar from University Hospital Zurich

Mussel Glue Could Help Repair Birth Defects

BOSTON—When it comes to hanging on tight, the lowly mussel has few rivals in nature. Researchers have sought the secrets behind the bivalve's steadfast grip on wet, slippery rock. Now, reporting here today at the annual meeting of AAAS (which publishes ScienceNOW), a researcher said he has used the mollusk’s tricks to develop medical applications. These include a biocompatible glue that could one day seal fetal membranes, allowing prenatal surgeons to repair birth defects without triggering dangerous premature labor.

To hold fast beneath the surging waves, mussels secrete liquid proteins that harden into a solid, water-resistant glue. What’s easy for the animals, however, has been hard for human engineers. Not even Super Glue will stick in a fish aquarium because a layer of water forms that keeps the two surfaces from bonding. But mussels somehow elbow the water aside and bind themselves to rocks anyway, Herbert Waite, a biologist at University of California, Santa Barbara, said today at the meeting.

Over 30 years, Waite’s team has uncovered the basis of this remarkable ability. Each of the 15 proteins that make up the mollusks’ holdfasts—thread-like structures that help attach the mussel to a hard substrate—contains an abundance of an amino acid called dihydroxyphenylalanine, or DOPA. DOPA is particularly abundant in parts of the proteins that face out toward the hard surface. It enables liquid holdfast proteins to solidify rapidly and stick flawlessly to wet and salty surfaces.

“If I were to list the desired properties for medical adhesives, they would look exactly the same,” said session speaker and materials scientist Phillip Messersmith of Northwestern University in Evanston, Illinois. He and his colleagues have created a synthetic, thread-like polymer called polyethylene glycol that mimics the mussel protein, and they've attached a synthetic form of DOPA to the thread’s tips. This DOPA-decorated thread could "more or less recapitulate the central properties of mussel adhesion," Messersmith said.

To see if the compound worked in live animals, a veterinary surgeon collaborating with Messersmith's team made a 2.5-centimeter incision in the carotid artery of a dog and placed four stitches along the length of that incision to hold it in place. With the stitches alone, the incision bled when the surgeon pressed it. But just 20 seconds after the mussel-based glue was applied, the artery was sealed and didn’t bleed.

More recently, Messersmith’s team began testing its glue on fetal membranes. For the past few decades, surgeons have begun surgically repairing birth defects like spina bifida while a fetus is still in utero. But the process is risky because the surgery risks rupturing the fetal membrane prematurely, sending the mother into premature labor. This can lead to the birth of a tiny, vulnerable preemie.

There are no good adhesives on the market for surgeons to repair such fetal-membrane tears, and that’s the major reason fetal surgery remains risky. But in recent, unpublished experiments in rabbits, Messersmith and colleagues found that after a veterinary surgeon poked a 3.5-mm hole in the animal’s fetal membrane, the new, mussel-inspired glue readily sealed up the puncture. What’s more, without the glue, only 40% of the fetal rabbits survived the surgery, but with the glue, 60% did.

In another recent result that’s in press at Advanced Health Materials, the researchers chemically altered the polyethylene glycol polymer so that the glue would shrink when it hardened. This could counter tissue swelling during surgery, which surgeons say is dangerous. And the fetal surgeons working with Messersmith are testing whether the glue can help reseal the tissue surrounding the spinal cord to repair a serious birth defect known spinal bifida in rabbits.

"It seems like exactly what you want to seal up an artery," says Emily Carrington, a biologist at the University of Washington’s Friday Harbor Laboratories who studies mussel adhesion and who did not take part in the research. The mussel-inspired glue is ideal, she added, because it is both strong and it has give. "I think it’s very exciting."