Worm Glue Can Seal Tissues

Sandcastle worms are pretty good chemists. Without advanced degrees, they have figured out how to biosynthesize glue components they use to build the underwater tubular shelters they call home. Inspired by the worms, Russell J. Stewart of the University of Utah and coworkers are now creating similar adhesives that might be used to make in utero surgery safer or to block blood vessels that feed tumors.

“It’s a classic example of borrowing successfully from nature,” comments biomedical sealants specialist Jeffrey M. Karp of Brigham & Women’s Hospital, Boston. “The Stewart group has taught the world how sandcastle worms achieve underwater adhesion and is now extending these discoveries to an approach that may find many practical solutions in medicine.”

When doctors examine or perform surgery on developing fetuses, the amniotic membranes that protect fetuses in the womb can rupture. The membranes often fail to heal, so the procedures carry a significant risk of preterm delivery.

Existing medical adhesives fall short in addressing this surgical predicament. Some adhesives swell too much when they cure, which can cause damage to the delicate amniotic membranes. Others “are ineffective in the flexible, moist, and biochemically active conditions of the human body or are acutely cyotoxic,” says Nick Aldred of Newcastle University, in England, who is an expert on adhesives made by barnacles.

Stewart told a Division of Agricultural & Food Chemistry session at this week’s American Chemical Society national meeting that he hopes a sandcastle-worm-inspired adhesive his group is developing will provide an effective alternative for existing adhesives.

Sandcastle worms produce highly charged polyelectrolyte glue components in different types of cells and then combine oppositely charged components enzymatically when constructing their shelters. Obtaining the glue directly from the worms or producing it recombinantly hasn’t proved practical. So Stewart and coworkers instead synthesize oppositely charged polyelectrolytes and combine them to form water-immiscible polymer solutions called complex coacervates. They then apply the coacervates to biological tissues and cross link them enzymatically to cure them into adhesives that bond to the tissues. The patented technique is in preclinical testing for use during fetal surgery.

The technique could also be useful for sealing blood vessels to cut off blood supply to tumors or for underwater industrial adhesive applications. “The fluid adhesives adhere to blood vessel walls and solidify under flow,” Stewart says.

“Not only are the glues demonstrably effective, but they seem to cause little if any immune or cytotoxic response,” Aldred said. “In my view, they have a lot of potential and, importantly, could be economical to produce.”

Stewart and coworkers “have made astounding progress in quickly moving from understanding the key concepts of wet adhesion by the sandcastle worm to the point where they are able to synthesize a polymer that mimics it,” said Anne Marie Power of the National University of Ireland, who studies barnacle wet adhesion. “It could address a real surgical problem.”