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Highly adhesive, elastic surgical sealant engineered from human protein

By Rachel Nuwer November 29, 2017
Highly adhesive
Histological staining shows how MeTro gel (on top), applied to an injured lung area tightly bonds and interlocks with the tissue surface. The elastic tissue is tightly sealed without need for additional sutures or staples. Credit: Nasim et. al.

Sutures, staples, and wires are often used to put tissues back together post-surgery. But they are not ideal, especially for hard-to-reach or delicate organs, and for those that regularly expand and contract, such as the heart, bladder, veins, and lungs. Piercings can also cause further damage and increase the risk of infection, and it often takes significant time to sew or suture a wound.

A newly developed super-elastic surgical glue bypasses these problems entirely. Engineered from human proteins, methacryloyl-substituted tropoelastin (MeTro) is light-activated and quickly solidifies. As described in the journal Science Translational Medicine, in vivo tests showed that MeTro effectively closed wounds on lungs in a pig animal model. Two weeks after application, the animals were healthy and the wounds were healed, with no signs of toxicity.

“This surgical material allows tissue to have normal movement during the healing process, which is very important,” says lead author Nasim Annabi, an assistant professor of chemical engineering at Northeastern University and a lecturer at Harvard Medical School. “Everyone who worked on this is very excited about the material’s unique properties.”

Annabi and her colleagues originally set out to develop a material for tissue engineering applications—one that could be used to regenerate damaged areas of the heart, for example. After discussions with colleagues at Harvard Medical School, the team became aware of an unmet need for an elastic surgical glue for effective sealing of lung tissues after surgical procedures. The researchers learned that while there are a number of surgical sealants already available on the market, these are mainly limited to external use or they must be used in combination with sutures. As soon as those sealants are exposed to blood or other bodily liquids, they lose their elasticity and adhesion.

Annabi and her colleagues were convinced that they could create a superior surgical glue that featured high elasticity, high adhesion, non-toxicity, and easy application. As a basis for the new material they settled on tropoelastin, a highly biocompatible, very elastic human-derived protein, which they obtain from biological synthesis. Tropoelastin does not contain any chemical binding sites that can be activated by polymerization, however, so they chemically modify it using a chemical compound called methacylic anhydride, which adds methacrylate groups to the amine-containing side groups of tropoelastin. This makes the protein suitable for photocrosslinking, allowing the researchers to create an elastic and adhesive hydrogel that forms upon exposure to light for less than a minute.

“The fact that surgeons use light to polymerize the material is great because it gives them time to decide where to inject the prepolymer solution and then crosslink it with light,” Annabi says. She adds that the sealant also changes viscosity as soon as it reaches 37°C upon contact with the body, thickening to prevent it from spilling outside of the desired area of application.

The team started with in vitro experiments and then moved on to ex vivo testing using explanted animal organs. In one experiment, they created an incision on a pig lung, sealed it with MeTro and then used a ventilator to inflate and deflate it, both in air and under water. The material could seal a defect point without leaking or bursting. They next moved on to in vivo experiments in rats and pigs, showing that they could effectively seal small to large holes in those animals’ lungs. Not only did all of the animals survive, but two-week follow-ups revealed that their organs were beginning to heal and that the MeTro was being broken down naturally by enzymes in the body, eliminating the need for a second surgery to remove it.

Annabi and her colleagues have already begun investigating ways to use visible light rather than UV light to activate the gel, and they also plan to further study MeTro’s degradation in the body to ensure it remains safe in the long term. If all goes well, they will then pursue US Food and Drug Administration (FDA) clinical testing to begin moving the material toward medical use in humans. Because MeTro’s physical properties can be tuned simply by changing its chemistry, they believe it can work for virtually any elastic organ in the body.

Others agree that the material holds possibility. “Sutures and staples have improved and saved many lives, but they are far from perfect,” says Jeff Karp, an associate professor of medicine at Brigham and Women’s Hospital, who was not involved in the research. “This is a very interesting technology that has significant potential for meeting some of the big needs for better tissue adhesives in medicine.”

Read the abstract in Science Translational Medicine.