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Inspired by the sticky substance barnacles use to cling to rocks, engineers at MIT have designed a strong, biocompatible glue that can seal injured tissue and stop bleeding.
The new paste can adhere to surfaces even when covered in blood, and can form a tight seal within approximately 15 seconds of application. Such a glue could offer a much more effective way to treat traumatic injuries and help control bleeding during surgery, the researchers say.
“We solve a problem of adhesion in a difficult environment, which is this humid and dynamic environment of human tissues. At the same time, we are trying to translate this fundamental knowledge into real products that can save lives, ”says Xuanhe Zhao, professor of mechanical and civil and environmental engineering at MIT and one of the study’s lead authors.
Christoph Nabzdyk, cardiac anesthesiologist and intensive care physician at the Mayo Clinic in Rochester, Minnesota, is also a senior author of the article, which appears today in Nature Biomedical Engineering. MIT researcher Hyunwoo Yuk and postdoctoral fellow Jingjing Wu are the lead authors of the study.
Natural inspiration
Finding ways to stop the bleeding is a long-standing problem that has not been adequately addressed, Zhao says. Sutures are commonly used to seal wounds, but setting up stitches is a tedious process that is not usually possible for first responders during an emergency. Among the military, blood loss is the leading cause of death from traumatic injury, and among the general population, it is the second leading cause of death from traumatic injury.
In recent years, certain materials capable of stopping bleeding, also called hemostatic agents, have become commercially available. Many of them consist of patches containing clotting factors, which help the blood to clot on its own. However, these take several minutes to form a seal and don’t always work on wounds that bleed profusely.
Zhao’s lab has been working to solve this problem for several years. In 2019, his team developed double-sided tape and showed that it can be used to close surgical incisions. This tape, inspired by the sticky material spiders use to capture their prey in wet conditions, features charged polysaccharides that can absorb water from a surface almost instantly, removing a small dry area that the glue can adhere to.
For their new tissue glue, the researchers were once again inspired by the natural world. This time, they focused their attention on the barnacle, a small crustacean that attaches to rocks, ship hulls, and even other animals like whales. These surfaces are wet and often dirty – conditions that make adhesion difficult.
“It caught our attention,” Yuk said. “It is very interesting because to seal the tissues which bleed, it is necessary to fight not only against humidity but also against the contamination of this outgoing blood. We have found that this creature living in a marine environment does the exact same thing we need to do to deal with complicated bleeding issues. “
The researchers’ analysis of barnacle glue revealed that it has a unique composition. The sticky protein molecules that help barnacles attach to surfaces are suspended in an oil that repels water and all contaminants found on the surface, allowing the adhesive proteins to attach firmly to the surface.
The MIT team decided to try to emulate this glue by adapting an adhesive it had previously developed. This sticky material consists of a polymer called poly (acrylic acid) embedded with an organic compound called NHS ester, which provides adhesion, and chitosan, a sugar which strengthens the material. The researchers froze sheets of this material, crushed it into microparticles, and then suspended those particles in medical grade silicone oil.
When the resulting paste is applied to a wet surface such as a tissue covered in blood, the oil repels blood and other substances that may be present, allowing the adhesive microparticles to crosslink and form a tight seal on the skin. wound. Within 15 to 30 seconds of applying the glue, with gentle pressure, the glue hardens and the bleeding stops, the researchers showed in tests on rats.
One of the advantages of this new material over the double-sided tape that researchers designed in 2019 is that the paste can be molded to accommodate irregular wounds, while the tape might be better suited to seal incisions. surgical procedures or attaching medical devices to tissue, the researchers said. “The moldable paste can flow and adapt to any irregular shape and seal it,” Wu explains. “This gives users the freedom to adapt it to irregularly shaped bleeding wounds of all kinds.”
Better bleeding control
In tests on pigs, Nabzdyk and his colleagues at the Mayo Clinic found that the glue was able to quickly stop bleeding in the liver and that it worked much faster and more efficiently than commercially available hemostatic agents. to which they compared her. It even worked when strong anticoagulants (heparin) were given to the pigs so that the blood did not spontaneously clot.
Their studies have shown that the joint remains intact for several weeks, giving the tissue less time to heal, and that the glue induces little inflammation, similar to that produced by hemostatic agents currently in use. The glue slowly reabsorbs in the body over months and can also be removed earlier by applying a solution that dissolves it, if surgeons need to intervene after the initial application to repair the wound.
The researchers now plan to test the glue on larger wounds, which they hope will demonstrate that the glue would be useful in treating traumatic injuries. They also envision that it might be useful during surgeries, which often require surgeons to spend a lot of time controlling bleeding.
“We are technically capable of doing a lot of complicated surgeries, but we haven’t really progressed so quickly in being able to control particularly severe bleeding quickly,” says Nabzdyk.
Another possible application would be to help stop bleeding that occurs in patients who have plastic tubes inserted into their blood vessels, such as those used for arterial or central venous catheters or for extracorporeal membrane oxygenation ( ECMO). During ECMO, a machine is used to pump the patient’s blood out of the body to oxygenate it. It is used to treat people with deep heart or lung failure. Tubes often remain inserted for weeks or months, and bleeding at the insertion sites can lead to infection.
The researchers received funding from the MIT Deshpande Center to help them work on commercializing their glue, which they hope to do after performing additional preclinical studies in animal models. The research was also funded by the National Institutes of Health, the National Science Foundation, the US Army Research Office through the Institute for Soldier Nanotechnologies at MIT and the Zoll Foundation.
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