Jeffrey Karp is an animal lover, but this fondness did not lead to any affinity for Pomphorhynchus laevis, a blood-sucking parasite that resembles a fat earthworm with a small cactus sticking out of one end. Karp, an associate professor of medicine at Harvard Medical School, was searching for ideas from the animal kingdom to solve human medical challenges when he stumbled upon the parasite in a Google search.
The spiny-headed worm invades fish and makes its home in a hapless victim’s intestines by sticking its spiked proboscis into the host’s tissue. It then anchors itself into the tissue by swelling that needle-like appendage.
Rather than being repulsed, Karp was inspired.
“I firmly believe that evolution is the best problem solver,” he says. “All we need to do is look around in our environment and we can find many examples of how nature has overcome seemingly insurmountable challenges.”
Nature as muse
This is not the first time Karp and his colleagues have borrowed ideas from the natural world. Previously, Karp helped develop medical adhesives based upon sticky gecko feet and porcupine quills. In this case, he saw potential for harnessing the spiny-headed worm’s needle-like, swelling proboscis as a new way for holding skin grafts in place or closing wounds. “There’s been minimal innovation over the past several decades for tissue adhesive,” Karp says. “Often, we focus on conventional approaches but clearly these are not working.”
Normally, tissue adhesion relies upon staples placed around the periphery of the skin graft. But fluid often accumulates in the space between the staples and the graft, causing it to lose direct contact with the underlying tissue and, often, to fail. This leads to a number of serious complications. Staples also make relatively large holes in a patient’s tissue, increasing the chance for harmful bacteria to invade.
With parasitic inspiration in mind, Karp and his colleagues got to work designing a synthetic equivalent to the spiny-headed worm’s anchoring proboscis. They described their results this week in the journal Nature Communications. The researchers knew their needle needed to be stiff enough initially to penetrate the tissue and to swell rapidly in order to be useful in time sensitive medical procedures.
They settled upon a double-layer design, with an inner core composed of polystyrene, a material common in plastic bottles, and an outer layer made out of polyacrylic acid, which gives baby diapers their expandable properties. To ensure only the tip of the adhesive needle would swell and thus anchor itself in place, they filled the tips of cone-shaped molds with the swelling materials, and then applied the polystyrene on top of that. The microneedles—each about the size of a couple of human hairs across—were then secured to a backing so they could be applied or extracted in a single quick step.
(An illustration of mechanical interlocking from a water-responsive dual-layered microneedle-based adhesive. Image courtesy of Karp lab.)
Better stick, lower chance of infection and more uses
In lab tests, the new needles revealed several advantages. The investigators showed that the needles could stick not only in skin but also in soft tissue like the intestines, meaning they have wide-ranging applications. The microneedles demonstrated about three and a half times the adhesion strength as conventional staples. The needle tips also could be twisted 90 degrees without causing damage or breakage. Because the tips swell to fill the tiny hole they create, the chances for bacterial infiltration will likely be reduced, too.
Finally, since the needles’ swelling is reversible, Karp thinks they may be used for targeted drug delivery. Researchers could load the needle tips with antibiotics or agents to promote tissue regeneration, for example, which could then be delivered directly into the tissue and graft when the needles are secured onto the patient.
The new technology is still in its infancy and must undergo testing in large animal models before Karp and his colleagues can begin investigating potential human trials. The researchers already filed for a patent for the needle’s design, however, and Karp thinks that human trials could begin within a few years if all goes well. The microneedles’ scalability, or the cheapness and ease at which they can be produced, also increases their potential application in the real world. “That’s where a lot of technology fails,” Karp says. “There’s an emphasis on proof of concept, or just showing that it works, not on designing something that can be adapted and scaled for millions of people.”
(Spiny-headed worms inspire surgical staples replacement. Image courtesy Karp lab via Science.)
Top Image: This is an artistic rendition of the spiny-headed worm, Pomphorhynchus laevis. Image courtesy of Karp lab.