Bioengineers from the University of Utah (www.utah.edu) announced a new glue that has the sticking power to adhere to bone at the American Chemical Society conference in Washington, D.C. It imitates glue from sandcastle worms, which build sturdy tube-shaped homes under the ocean from bits of sand and shell and their own natural glue.
Professor Russell Stewart (rstewart@eng.utah.edu ) and his colleagues found that the sandcastle worm exploits changes in pH level to trigger the glue to harden. Inside the worm, where the pH is low, the glue is a fluid. Exposure to seawater, which has a higher pH, causes the glue to slowly solidify. Prof. Stewart expects that the synthetic worm glue will be tested on animals within a year or two, and will be tested and used on humans in five to 10 years.
The synthetic sandcastle worm glue would not repair large fractures such as major leg and arm bones. Prof. Stewart envisions that it might glue together small bone fragments in fractured knees, wrists, elbows, ankles and other joints, and also the face and skull.
After a little tinkering, the researchers recreated a synthetic version of the worm's adhesive – a polyacrylate glue that is water soluble but does not dissolve in liquid, is at least as strong as Super Glue, and is twice as strong as the worm's original glue. Cell culture experiments showed no sign of toxicity; early tests in rats appear to back that up and also show no unusual immune reaction.
The synthetic glue also can carry drugs, so it could deliver pain killers, growth factors, antibiotics, anti-inflammatory medicines or even stem cells to sites where bone fragments are glued, "simultaneously fixing the bone and delivering potent drugs or even genes to the spots where they are needed," Stewart says.
And where pieces of bone now are cut out due to cancer, the adhesive might firmly attach "tissue scaffolds" that encourage regrowth of the missing bone.
The adult sandcastle worm is an inch or so long, and an eighth-inch in diameter. But they build tubes several inches long, of sand grains and shell fragments. Tiny, hair-like cilia brush the sand grains and shell pieces down the tentacles so they can be grabbed by the worm's fleshy, pincer-like "building organ" and glued onto the under-construction tube piece by piece.
The worm "secretes two little dabs of glue onto the particle," says Stewart. "And the building organ puts it onto the end of the tube and holds it there for about 25 seconds, wiggling it a little to see if the glue is set, and then it lets go. The glue is designed to set up and harden within 30 seconds after the worm secretes it."
The sea worm's glue is made from two proteins – one acidic or negatively charged, the other basic or positively charged – that are natural polymers, or compounds with a repeating, chain-like structure. The glue also contains positively charged ions of calcium and magnesium.
In the natural worm glue, each protein polymer's "backbone" is made of polyamide, which has "side chains" of other chemicals attached to the backbone.
Instead of polyamide for the "backbone" of polymers in the synthetic glue, Stewart chose water-soluble polyacrylates, synthetic polymers that are related to commercial superglues. The "side chains" attached to the synthetic glue's polymer backbones copied the natural worm glue's side chains chemically and in other ways. Some side chains are dopa, which makes the glue function as glue.
"We made polymers with side chains that mimicked the positive and negative charges in the worm glue," Stewart says.
When the polymers are mixed, they form an unusual substance known as a "coacervate," which condenses out of the polymer solution and sinks to the bottom of a test tube as a dense solution that is the foundation of the synthetic glue. The two polymers in the coacervate "cross link" – their side chains attach to each other – forming chemical bonds that make synthetic worm glue harden. Because the solution-within-a-solution does not disperse, it can be sucked up with a syringe. "In some cases we may be able to repair bones with a syringe rather than screws and power tools," says Stewart.