Even with modern medicine’s advances, doctors still seal wounds with techniques seemingly more appropriate for craft circles than the operating room: staples, sewing kits and glue. Thanks to a new invention, the science of medical adhesives may get a modern revamp. Researchers literally turned over stones to devise a new super-strong glue from an unlikely source—slugs.
The current gold standard in medical adhesives is none other than superglue. The active compound in superglue, cyanoacrylate, is the toughest substance out there, but being strong is about all it has going for it. Superglue won’t stick to wet surfaces, which tends to be a problem with bleeding wounds. Once applied to a dry surface, it solidifies immediately into a stiff and unyielding plastic that breaks instead of moving with the body during healing. To top things off, it can be toxic to living cells.
“Sometimes it’s surprising, isn’t it?” says David Mooney of the rustic suturing methods available to doctors. Mooney is a professor of bioengineering at Harvard University whose research looks to the natural world to design new materials for medical applications. “Over the evolutionary process organisms have to face a number of different situations,” he says. It might take a million years, but in that time an organism can find the most elegant and effective way to rebuild a shell or patch a wound. Humans reach for a staple gun.
Mooney and his team try and bring a little bit of the animal kingdom’s finesse into man-made solutions to problems. They call it “bioinspiration.” Jianyu Li, a postdoctoral fellow in Mooney’s lab, started the search for an exemplary candidate that was a bastion of the strength and flexibility needed to seal wounds and save lives in a surgical setting. After poring over the literature, “[we] found this very fantastic creature,” Li says. “The slug.”
Arion subfuscus, the slug in question, might seem like an unlikely candidate. These unassuming, rusty orange molluscs lead a simple life in gardens and underneath logs in northern temperate regions around the world, minding their own business. That is, until something messes with them. If a hungry predator tries to take a nibble, the slug detonates a cache of defensive mucus.
“When I discovered these slugs and picked one of them up, I knew this material was really amazing,” says Andrew Smith, a professor of biology at Ithaca College and an expert in the biochemical properties of mollusc mucus who was not involved in the study. “It literally oozes off the back of the slug and sets in seconds into a really tough, elastic gel,” he says.
“The thing that makes it exciting is that the material is very tough,” Smith says. It can be stretched more than 10 times its own length, like a rubber band that won’t snap. It can harden, but remains flexible. Unlike superglue, it’ll work on wet surfaces. And it’s super, super sticky. In fact, Smith is still struggling to de-gunk his lab equipment.
Transfixed by the power of the mucus, he set out to figure out how it worked.
“A typical gel like Jell-o is stiff, but it’s brittle—if you press a spoon on it it splits,” Smith says. The slugs have figured out a way to be strong where gelatinous desserts are weak. He discovered that the mucus is 97 percent water, but woven through with two different polymers. The first is organized like a mesh net; it provides the strong backbone. Tangled through the mesh are extensive polymer chains that keep the mesh knitted together when stretched long distances. This so-called double matrix is the key to the strength and flexibility of the slug’s mucus.
Then the slugs make the whole thing sticky by lining it with positively charged proteins that act like atomic velcro, binding it to the negative charges on tissue surfaces. The net result? A mouth full of impermeable glue when a predator goes in for a slug snack. Or, the perfect inspiration for a novel, ultra-strong medical adhesive.
Based on Smith’s work characterizing the slug mucus, Li set out to replicate its properties in a synthetic adhesive. Mooney and Li point out that no garden critters will ever be harmed to make their invention. “We don’t have any element of slug mucus in our material,” Mooney says. “We used it as inspiration.”
After a few years of trial and error, Li produced a prototype that perfectly mimicked the slug’s durable double matrix properties, which they describe in a study out today in the journal Science. The top layer is a hydrogel that can be cut to the size needed. The second layer is applied as liquid to the hydrogel and activates the chemical bonding. “It’s Scotch tape that’s attached to something very elastic and can move readily with tissues,” Mooney says.
The new adhesive hits the sweet spot when it comes to timing in a surgical setting as well. “It’s not like if you accidentally touch it to your skin it’s stuck and you can’t get it off,” Mooney says. Surgeons would have about 10 seconds to get the adhesive into place. Once set, the adhesive “can accommodate the stress and strain experienced by the tissues,” says Li—strains like a beating heart, breathing, and movement.
With a prototype, the team put its adhesive to the test. They performed mechanical stretching experiments, used the adhesive to patch up injured rat livers, and even demonstrated its strength in sealing a large defect in a beating pig heart. In every trial their slug-inspired adhesive outperformed all the commercially available products, moving flexibly with healing livers and pumping hearts, all with no toxicity evident.
The team’s strategy of looking to nature to solve problems is a value shared by Phillip Messersmith, a professor of bioengineering and materials science at the University of California Berkeley whose research uses mussels as bioinspiration for adhesives. “It’s really a very important study,” he says. “Very well executed, and with important implications for medical applications.” Though Messersmith had no technical reservations, he notes that any future surgical applications will require the material to be biodegradable.
Luckily, a biodegradable version of these adhesives is next on the docket. With a patent pending, Li and Mooney also plan to assess whether their invention could be used safely in people. “In human patients, safety is paramount so there will be long term studies to have a high level of confidence in safety,” Mooney says. They’re also developing a version of the adhesive that can be injected into hard to reach places that need patching up. Inspired by an unassuming slug under the rocks in your garden, it seems the sky’s the limit for this invention.
“We’ve been working on the slugs for a while, and I’ve been really confident that this was going to lead to something good,” Smith says. “I’ve always felt that this slug was remarkable and had potential to lead to really useful glues, and wow—they really showed.”