How do you mend a broken heart? You’re operating on a heart and it’s got a tear in it. How do you seal it?
Sutures? Staples? These are the traditional answers, but they aren’t good ones. Both involve piercing tissue and creating holes, which is bad news for an organ that’s constantly moving, and vigorously pumping blood. Holes lead to clots. They also bleed.
And if you specialise in doing heart surgeries on babies, as Pedro del Nido from Boston Children’s Hospital does, you can add small size and delicate tissues to those other challenges. “The holy grail for heart surgeons, especially for those who work on babies, is to attach things without damaging the normal underlying tissue,” he says.
A glue, then. The trouble is that a heart adhesive must be strong enough to hold despite the heart’s constant beating, but flexible enough to allow those same beats to happen. It has to work in wet conditions—something that most glues aren’t designed to do. It needs to repel water so it doesn’t dissolve. It must thicken slowly or blood will wash it away. It can’t thicken immediately because you want to be able to position and adjust it. It has to be biodegradable.
These design specifications are an engineer’s nightmare, which explains why viable heart glues don’t exist. That is, until now.
Working with del Nido, Jeff Karp at the Brigham and Women’s Hospital and MIT’s Bob Langer have created a glue that ticks all the boxes. It seals heart tissue and blood vessels, it’s strong but flexible, and it’s made only from naturally-occurring substances already found in the body. It can be applied as a viscous gel, and then hardened into a strong adhesive with a burst of ultraviolet light. And, best of all, it works in flowing blood.
“I’m very excited about this project,” says del Nido. “There’s a huge clinical need for it. It’ll allow us to do much more sophisticated reconstructions than what we can do today.”
Karp has a history of making “bioinspired” adhesives, from sticky tape based on a parasitic worm to medical needles based on a porcupine’s quills. This time, he drew inspiration from several animals that can stick to wet surfaces. Insects, for example, often secrete viscous, water-repellent substances from their feet, which push water out of any gaps in the underlying surfaces. Meanwhile, the sandcastle worm builds underwater tubes by exuding a glue from its head. This substance is also water-repellent and viscous, and hardens over time into a strong adhesive.
The team realised that they had already made something similar—a substance called PGSA. It’s a union of glycerol, a basic building block of fats and oils, and sebacic acid, which is produced when certain fats break down. The team had originally made PGSA to create scaffolds on which they could grow new tissues or organs. (See here for Langer’s work on growing organs.) “We had hints that it could adhere to tissue but we never tested that,” says Karp.
Working with del Nido, Karp and Langer tweaked the formula of PGSA to create a viscous liquid that could be easily spread but would hold its shape. They also added a substance that creates bridges between the PGSA molecules on exposure to ultraviolet light, quickly curing the glue on demand. “Other adhesives like crazy glue cure immediately in the presence of moisture or water,” says Karp. “Ours doesn’t. We can place it in a very wet environment completely filled with blood and it only becomes adhesive when we cure it with light.”
These traits give the glue time to seep in between the fibres of the underlying tissues, displacing water along the way. That’s why it’s so strong once it hardens—it’s part of the tissue, rather than just a layer on the surface.
The new glue outcompeted cyanoacrylate, or super glue, in several tests: it stuck better, it swelled less, and it triggered less inflammation. “This is a major feat, as super glue is considered to be the strongest tissue adhesive around,” says Christian Kastrup from the University of British Columbia. The only potential damage comes from the ultraviolet light, which is infamous for its ability to damage DNA. Still, a five-second burst is unlikely to do much lasting harm.
Karen Christman at the University of California, San Diego, says the technology is exciting, but that “several preclinical tests need to be performed before translation to patients.” First and foremost, they need to check that it’s safe for use inside actual hearts. “It is also unclear if this could work with Gore-Tex patches, which are one of the most common patch materials used for the heart,” she says. “If this is possible, this could definitely make surgeries easier considering there is often bleeding at the suture lines with these synthetic patches.”
The team is on the case. So far, they have successfully tested the glue in four live pigs, using it to attach patches to their beating hearts, and to seal damaged carotid arteries. The animals survived, fared well, and showed no signs of clots or bleeding after the operations.
A Paris-based company called Gecko Biomedical has now licensed the technology and raised 8 million euros to bring it to market. They’re now scaling up the manufacture of the glue and, once that’s done, they hope to move to clinical trials. If it succeeds, Karp hopes to put it in the hands of clinicians within three years. For his part, del Nido wants to see if the glue can stop blood from leaking from holes around sutures. If that’s safe and effective, he will move on to more complex things.
This isn’t just about hearts, either. Karp suggests that the glue might also work in the gut—another environment characterised by lots of liquid and constant movement. “It really opens the door for more minimally invasive approaches,” he says.
Reference: Lang, Pereira, Lee, Friehs, Vasilyev, Fein, Ablasser, Cearbhaill, Xu, Fabozzo, Padera, Wasserman, Freudenthal, Ferreira, Langer, Karp & del Nido. 2013. A Blood-Resistant Surgical Glue for Minimally Invasive Repair of Vessels and Heart Defects. Science Translational Medicine. Vol 6 Issue 218 218ra6