The biocompatible adhesive was inspired by the glue secreted by slugs.

Medical adhesives are critical for the treatment of injuries to the skin, but current solutions have significant limitations, according to researchers at Harvard University. They often don’t stick to wet skin and are toxic to cells, inflexible when they dry and do not bind strongly to biological tissue. These scientists at the Wyss Institute for Biologically Inspired Engineering and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed an alternative that is not only very strong, but also biocompatible and binds to tissues even when they are wet.

The “tough adhesive” binds with a strength comparable to that of human cartilage, according to the researchers. The inspiration for the adhesive was less attractive. The mucus secreted by the Dusky Arion (Arion subfuscus) slug (common in both Europe and parts of the US) when it is threatened was previously shown to act like a glue, keeping the slug stuck to the surface and making it difficult for predators to remove it. The glue is made of positively charged proteins in a tough matrix.

Jianyu Li, formerly a Postdoctoral Fellow at the Wyss Institute and now an Assistant Professor at McGill University, decided to create a synthetic version of this glue as an adhesive. The new medical adhesive is composed of a double-layered hydrogel. An alginate-polyacrylamide matrix supports an adhesive layer containing positively-charged polymers protruding from its surface. 

The polymers can bind to biological tissues in three different ways–through electrostratic interactions with negatively charged cell surfaces, covalent bonds between neighboring atoms, and physical interpenetration. As a result, the adhesive is very strong. The matrix, which incorporates calcium ions bound to the alginate hydrogel via ionic bonds, provides a mechanism for dissipating energy (through breakage of the ionic bonds), enabling the adhesive to deform significantly before it breaks, according to Li.

“The key feature of our material is the combination of a very strong adhesive force and the ability to transfer and dissipate stress, which have historically not been integrated into a single adhesive,” says corresponding author Dave Mooney, Ph.D., who is a founding Core Faculty member at the Wyss Institute and the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

The researchers were able to show that more than three times the energy was needed to disrupt the tough adhesive’s bonding, when compared with other medical-grade adhesives. In addition, when the new adhesive did break, it was the hydrogel that failed, not the bond with the tissue. Tests were conducted on dry and wet pig skin, cartilage, heart, artery, and liver tissues. The adhesive bonded to all of them more strongly than other medical adhesives. It was also implanted in rats where it maintained its performance for two weeks. Additionally, the adhesive was able to seal a hole in a pig heart and withstand tens of thousands of cycles of inflation and deflation. The adhesive was shown not to cause tissue damage or adhesions, problems observed with both super glue and a commercial thrombin-based adhesive when used to repair a liver hemorrhage in mice.

Potential applications for the new adhesive are quite varied, from patches that can be applied to a surface to injectable solutions that can be used to repair deep injuries to the “glue” for attaching medical devices within the body. “This family of tough adhesives has wide-ranging applications,” says co-author Adam Celiz, Ph.D., who is now a Lecturer at the Department of Bioengineering, Imperial College London. “We can make these adhesives out of biodegradable materials, so they decompose once they’ve served their purpose. We could even combine this technology with soft robotics to make sticky robots, or with pharmaceuticals to make a new vehicle for drug delivery.”

“Nature has frequently already found elegant solutions to common problems; it’s a matter of knowing where to look and recognizing a good idea when you see one,” says Wyss Founding Director Donald Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, as well as a Professor of Bioengineering at Harvard SEAS. “We are excited to see how this technology, inspired by a humble slug, might develop into a new technology for surgical repair and wound healing.”