Jeffrey Karp, Brigham and Women's Hospital, Harvard Medical School
When surgeons need to operate on the heart and cardiovascular system, minimally invasive procedures are often the best way to avoid complications and reduce recovery time for patients. But if you reduce the space that you’re working in, you also reduce the space you have to use sutures and staples.
This week a team announced they had developed a light-activated blood-resistant glue for use in just these scenarios. We were joined by Jeffrey Karp from the Harvard Medical School.
Chris - So what is wrong with the glues that currently surgeons and doctors have to use on tissue? Why do you need to invent a new one?
Jeffrey - Sure. Well you know, we’ve been using staples and sutures for decades and there's been really minimal innovation. They have inherent limitations. As you mentioned, they're difficult to place in small spaces like during laparoscopic or minimally invasive procedures. Also for glues, there's very few glues that actually have been approved for medical use. One example of a glue that's approved is a medical grade crazy glue or super glue. It’s only been approved for minimal uses. When you use it inside the body, you actually have to dry the tissue before you apply it because it’s just so highly reactive. And so, this essentially means you can't use it for most applications that clinicians would like.
Chris - So, what inspired you to solve some of those problems and come up with this new glue?
Jeffrey - So, I've been working closely with Dr. Pedro del Nido who’s the Chief of Cardiac Surgery at Boston Children’s Hospital. He’s been trying to seal septal defects which are holes that occur between the chambers of the heart and 1 in 100 babies that are born have some form of congenital defect. The ones that require surgery typically, a non-degradable device is put in and it needs to be changed every few years because it just doesn’t grow with the patient. And so, what we were interested in doing is coming up with a new type of adhesive that would allow us to seal these holes using fully biodegradable materials that would work in the presence of blood in such a challenging environment inside the heart.
And so, what we did initially is we came up with a long list of design criteria for a solution and we wanted the material to be biodegradable. We wanted it to be elastic because the heart continuously expands and contracts, multiple cycles. We wanted it to be non-inflammatory so when we would implant it, it wouldn't promote a strong inflammatory response. And then we also turned to nature for some inspiration. So, if we look into nature, there's many examples of insects and other critters on land and even in the ocean. What we noticed is that, if you look at these collectively, many of these creatures have secretions and those secretions are highly viscous. So, when they are placed onto a surface, they don't really move too much. If you look carefully at these secretions, they also contain agents that repel water. And so, what we thought would be, “Could we develop something that would initially be very viscous, kind of like honey, but then also, repel blood and water away from a surface?” So, as soon as you applied it to a tissue, it would repel the blood away from that tissue and then it would stay there even in flowing blood conditions such as inside the heart.
Chris - How would you deploy it? So, if you had a defect in the heart as you have outlined in these children, how would you get the glue into the right place and then make it set?
Jeffrey - So, this is something that we've thought quite a bit about. So, we designed this glue with that in mind. So, the idea is that because it’s viscous, it’s in a liquid state. So, we can inject it. We can even paint it on. We potentially could spray it. We’ve also shown that we can place this onto the surface of a patch-like material and then we can deploy this. So, in some instances, we may use the glue alone by injecting through a minimally invasive device for example. In other instances, we can coat it on the surface of a patch and even a biodegradable patch so the entire system, the glue, and the patch will degrade.
Chris - How sticky is it because the pressures generated for instance in the heart or an artery are extremely high, can it withstand that?
Jeffrey - Absolutely. So, that was one of the other design criterias is that not only do we want this to stick, but it needs to be strong enough to close holes in these dynamic environments. And so, in one example, we actually created a hole in a rat heart and then we were able to seal it. So, it was a sizeable hole in the heart of the rat. We were able to seal that wtih just pure glue alone. We took the animals out to 6 months and they did fine.
Chris - Is there not a risk that this stuff, being very sticky but also being very gelatinous could break off from where you've deployed it and then go down a blood vessel and effectively block up a blood vessel, therefore, depriving the tissue downstream of oxygen and blood flow?
Jeffrey - Sure. There's always these types of risks exist, but what we were able to show in our studies is first of all, we didn’t see such instances of these types of complications occurring. And also, these materials are very biocompatible. What that means is that cells and tissue can grow over them very quickly. And so, right after we place this glue into the heart or onto the surface of a blood vessel for example, within just a few days, it’s already starting to be coated with cells and other tissue. So, that will significantly limit the potential for chunks to break off, as you say, and cause an embolism or a stroke.
Chris - And how do you actually make the glue set where you want it to?
Jeffrey - What happens is that wherever we inject the glue, as soon as it hits a surface, because it’s so viscous, it just stays there. Then also, what we found which was quite fascinating is that the glue is able to penetrate into the tissue. So, it actually goes into the tissue fibres and then when we shine UV light, this actually cures and locks the glue into place.
Chris - And there's no danger to the tissue through having ultraviolet light shone on it?
Jeffrey - We’ve shown that we can shine a fairly low level of intensity of light over a short period of time. So typically, it only takes maybe 5 to 30 seconds to get a complete cure. So we, in our initial experiments, we actually looked at this in extensive detail and found intensities of light that did damage the tissue. But then we were able to scale that back and it still achieved a strong fast cure without doing damage to the tissue.