A Biomimetic Patch Could Soon Change the Way We Do Heart Valve Repairs
David Kalfa, MD, is a pediatric heart surgeon with a PhD in tissue engineering. As Surgical Director of the Initiative for Pediatric Cardiac Innovation, his passions align in the thoughtful development of creative solutions to clinical problems.
We spoke to Dr. Kalfa about a recent breakthrough in the Cardiothoracic Research Lab, the first synthetic patch for heart valve repair that actually mimics the natural valve’s complex structure and function.
Editorial Note: Since published, Dr. Kalfa’s development of a biomimetic multilayered polymeric material designed for heart valve repair and replacement has been published in the journal "Biomaterials," the highest impact-factor journal in the field. The work also was accepted for oral presentation at the Congenital Heart Surgeon Society summit in Chicago, October 2022.
Before we get into the biomimetic patch, how do you treat valve malformations currently?
Malformation of heart valves is very frequent in children, and there are different ways to address that—you can either do a repair of the valve or do a replacement of the valve. When you try to do a repair, very frequently the leaflets are restrictive, not very mobile. So, you have to augment them to make them more mobile or to add some length, to improve the coaptation or the functioning of the valve.
How does that work?
You need to add more tissue sometimes, which means we have to do either patch augmentation of the leaflet or leaflet replacement. There is another situation where we have to replace the valve, but by recreating three leaflets ourselves. This is what we call the Ozaki technique or aortic valve neocuspidization.
For all these repairs, including the Ozaki technique, we use patches, biomaterials. But they are not living materials.
Are they bovine or from another animal?
They can be autologous tissues—tissues coming from the patients. So, for example, we usually use the patient's pericardium [the membrane around the heart]. And then you have certain other patches that you just mentioned—pericardium from cows or pigs. But none of these patches are optimal because they tend to degenerate and calcify with time.
So, the durability of these patches that are currently available, commercially available, or that you can take from the patients are not good, the durability is pretty bad. And they're pretty bad because of degeneration, calcification… But also because of mechanical failure of the patches.
When you create the patch from the patient's own pericardium, are you doing that in OR during repair surgery? Taking part of the pericardium and cutting the leaflets?
Yes. At the beginning of the case we can take small pieces of pericardium and we have to treat it to make it a little bit more resistant, basically, and then we keep working on the operation. Then at some point, we can use it when it's ready. We usually treat it between 2 and ten minutes depending on the indication.
Tell us about the biomimetic patch. How is it different?
Okay, so none of these patches are good, none of them are durable. So, there is a real clinical need to get a new patch. And our hypothesis here is that if we are able to create the patch that has the exact mechanical properties and the same architecture of the native leaflet, biomimetic, then such a patch could be and should be more durable.
What does that mean exactly? What’s the architecture of the native leaflet?
So, the leaflet of the valve is a very highly organized structure with three layers. And each of these layers is also extremely well organized. One layer has collagen fibers oriented in a specific direction, and the other layer has elastic fibers oriented into a perpendicular direction to the first one. The spongiosa layer is a sponge, as it is called, and plays a specific role in this highly organized structure by absorbing the shock and the stress.
And that highly engineered structure is designed, or has evolved, to handle the blood flow?
Yes, it's all about how to be a sustainable structure that can open and close millions and millions and millions of times during the life of someone.
How long do each of the other patches that you're currently using last?
That depends. The younger the baby is at the time of the implantation, the less durable the patch is because there is more calcification. So, depending on the type of patch, I would say that it can degenerate as soon as something like a few months, three or six months after the surgery. Sometimes it's much better and it can take some five years to degenerate, but let's say between three months and five years.
With this new biomimetic patch, how long do you estimate it should last?
Hopefully forever! Our patch has to be exact in being biomimetic. We have shown that it mimics the architecture of the native leaflets and that it has the exact same mechanical properties of the native leaflet. It’s made of an inert polymer or biostable polymer with anisotropic properties.
Explain anisotropy, what does that mean?
Anisotropy is a very, very important characteristic of the native leaflet; and anisotropy means that the mechanical properties of this native leaflet are in different directions. They are directionally dependent. If the leaflet is pulled one way, and then pulled in another direction or the opposite way, it will react differently depending on direction.
So, the mechanical properties are extremely important for good function of the valve. None of the currently available patches have anisotropy and we basically designed our patch to get anisotropy. It is anisotropic.
How does that work in terms of how blood flows through the valve long term?
It means that the valve will work in a better way from a hemodynamic standpoint with less risk of obstruction in the coming months and the coming years. And less risk of leakage or regurgitation of the valve in the coming years. Bottom line, it's better functioning of the valve to preserve the function of the heart. If you have a significant obstruction or leakage of the valve, at some point the heart will fail, and this is heart failure.
Wow. Is this biomimetic material completely new?
This is the first time that we surgeons have a material that can mimic that. We did in vitro [laboratory] testing to prove the biomimetics, the biostability, and biocompatibility of the patch. And we showed that these patches are as biostable and as biocompatible as FDA approved biomaterials. And then we also implanted this patch in rats just under the skin to show that these patches do not calcify and do not expose to an inflammatory reaction. So, the next step would be to implant that in a heart valve in a large animal model. We will replace one of the leaflets of the pulmonary valve or the aortic valve in a sheep and see how this patch performs in vivo in good position.
That’s exciting. Are there other ways you hope you use this material too?
Oh, yes. It is exciting! We could potentially think about doing a valve, a 3D flat valve using these biomaterials. If this biomaterial can function as a native leaflet, you could think about creating a valve device, not only a patch but a valve device out of this material.
With so much progress in the lab, what does this mean for patients today?
This would be a disruptive technology—it would change dramatically the way that we think about and how we do valve repair. Because of the bad outcomes of currently commercially available patches, surgeons prefer to avoid the use of patches during a valve repair as much as we can. We know that it will fail at some point. But if we have an optimal patch with optimal durability, then we can shift the paradigm of valve repairs, in both children and adults.
Having a patch that's reliable like this, how would that change surgery and recovery?
It would avoid multiple re-operations for the patient. Because of the mechanical failure or biological degeneration of the current patches, we have to re-operate many times, or do a valve replacement, which comes with other limitations. So, it would mean fewer re-operations, no use of anticoagulant therapy, and fewer complications and hospital admissions related to this operation.
Is that what excites you most about the patch?
Absolutely. The clinical outcomes, the potentially huge impact for our patients, that's really what drives this project and all my projects. It's really clinically driven. We’re doing translational research; you identify an unmet clinical need and then based on that, you try to find solutions to improve outcomes for patients. It’s very, very exciting.
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