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Medicine is rapidly advancing as various scientific discoveries are implemented into everyday medical practice. One of the most recent fascinating developments are growth-accommodating implants: therapeutic medical devices manufactured to replace, support or enhance a part of the body while not restricting its growth.
A brief introduction to the heart
Cardiovascular diseases are some of the most common diseases patients suffer from. Our heart is a fairly simple organ behind which stands complex machinery which needs to operate with impossible precision. The human heart consists of four empty chambers: two upper chambers, also known as atria and two lower chambers, also known as ventricles. The chambers are separated by heart valves – one-way valves which allow blood to pass from the atria to the ventricle, but not in the other direction. The right atrium is the place where unoxygenated blood arrives from all the veins in our body. Then, under the pressure generated by the constriction of the atrium, the unoxygenated blood goes from the right atrium to the right ventricle through the tricuspid valve. After that, when the ventricles contract, the unoxygenated blood is set on its way to the lungs through the pulmonary valve and the pulmonary arteries, where it gets oxygenated before it arrives back at the heart through the pulmonary veins, this time to the left atrium. From there it passes through the mitral valve to enter the left ventricle and, ultimately, the aorta through the aortic valve, from where it circulates through the entire body and delivers oxygen to hungry tissues.
The valves are a crucial part of the heart apparatus since they are the ones who dictate the flow of blood. If they did not exist, the blood would go from the atria to the ventricles and back since it is much easier for it to go between the two chambers instead of into the narrow arteries leading out of the heart. To prevent this, the heart has a way to regulate the flow of blood with anatomy alone. The tricuspid valve has three cusps or leaflets, and the mitral valve has two of them. These leaflets are made of cartilage and are connected to fibrous rings (or annuli) from one side, and by tendinous cords to the papillary muscles on the other side. That way, when the blood flows from the atria to the ventricles, the valve opens due to the pressure created by the blood and the cords contract, helping with the widening of the gap. When blood tries to flow backwards, into the atria, the leaflets close and stop retrograde flow.
Heart valve insufficiency
As you can imagine, if one of the valves is too big for the leaflets to be able to completely close off the passage for backward flow, a bunch of problems arise. That condition is medically called heart valve insufficiency because the valve’s ability to close the gap is insufficient to do it properly. In that case, some blood can escape back to the atria and can become inaccessible to the body, which is medically called regurgitation. Because of that, the body must react, so it forces the heart to work harder and faster – to increase the blood flow and the amount of oxygen which needs to get to the oxygen-hungry tissues.
Some common causes of valve insufficiency in adults are rheumatic fever, infections, high blood pressure, genetic conditions and many other diseases. The way valve insufficiency is treated in adults is primarily by lifestyle changes (losing weight, exercising, eating a healthy diet), if your condition is mild and reversible. If it is severe and irreversible, you are eligible for valve replacement or valve repair by annuloplasty. This is a procedure during which the fibrous rings around the valve (the annuli we mentioned before) are shrunk or constricted by the insertion of a prosthetic ring so the valve can operate normally again. Such prosthetic rings are commonly made of plastic, metal or fabric, depending on how rigid or flexible they need to be. This surgery might sound reasonably simple, but it is really complicated in reality. It can be done endoscopically or during open-heart surgery which consequently requires a long recovery period.
Prosthetic ring implants – adults vs. children
The annuloplasty in children is frequently avoided because it cannot accommodate the growth of the heart. If the same condition appears in a child, which can be the result of some infection or autoimmune disease, the approach currently is totally different from the adult version. To be clear, the ring implants are not a perfect solution in either case. In adults, after a couple of years, the rings can tear or break which needs to be promptly repaired by another annuloplasty, which in and of itself is a difficult maneuver. In children, the most common way to treat this condition by annuloplasty is by doing multiple procedures one or two years apart when the heart grows enough to make the valve too narrow to let a sufficient amount of blood into the ventricles. This is very hard on the growing child, especially since the recovery periods are so long the child might struggle to have a normal life. That is why a miraculous invention in this field was needed to make the lives of children with this condition much more enjoyable.
Growth-acommodating implant for children
A promising invention by Feins and his team is a growth-accommodating implant which can grow as a child’s heart grows. This would eliminate the need for multiple heart surgeries on children and therefore significantly improve their quality of life. The implant consists of a biodegradable core and a braided sleeve. This design ensures that during growth, the core dissolves under the forces generated by the growing heart, and the braided sleeve extends just enough to keep the width of the fibrous ring exactly the size it needs to be.
The ideal growth-accommodating device should:
- Achieve tissue/organ repair like current fixed-size devices
- Gradually and continuously elongate in concert with native tissue growth in children
- Possess a tunable and predictable elongation profile to enable disease- and patient-specific application
- Be mechanically strong enough to withstand physiological stresses throughout growth after implantation
- Possess a non-degradable element that remains implanted to provide long-term tissue support once the organ has completed growth
- Be simple in design to facilitate rapid translation to clinical application
Structure – ESPGS core and UHMWPE braided sleeve
The structure was determined to be as straightforward as it can be – they chose a biaxial braid as the outer sleeve because its transformation of diameter change into length change can be precisely tailored to generate distinct elongation profiles, or – in other words – the way the diameter changes is very customizable. It is also porous enough to allow access of bodily fluids to the biodegradable polymer core for degradation, but strong enough to stably contain the core. The UHMWPE in the name stands for ultra-high molecular-weight polyethylene.
The ESPGS (extra-stiff polyglycerol sebacate) core was chosen because of its very predictable degradation. By changing various steps during the process of manufacturing the core, its degradation can be finely tuned to the individual child’s need.
Experiment: piglet annuloplasty
When the growth-accommodating implant was created, it had to be tested before it could be used in people. That is why the team decided to try it out first on piglets. They took four growing female Yorkshire piglets which underwent surgical implantation of the ring. They were studied for 5, 12, 16, and 20 weeks to assess device behavior and valve growth. They performed tricuspid valve annuloplasty, rather than mitral valve annuloplasty because it can be done with the heart still beating and with a lower risk of complications.
The ends of the braided sleeve were anchored to the fibrous ring, or annulus, with sutures (exactly as shown in the picture about mitral valve surgery), and additional sutures were placed through the valve fibrous ring and around the ring along its length. This enabled the annulus to be downsized and the ring to be placed right next to the annulus, as is typically achieved in heart surgery. When the implant was explanted and inspected, it showed areas of significant polymer core erosion. The valve was effectively downsized by the growth-accommodating ring prototype at the time of surgery. To be clear, even though it was a great success, there are still problems with this method that need to be addressed. First, the ring was covered with fibrous tissue after a few weeks which affects the speed of the polymer degradation and can therefore mess with the calculated expansion of the ring. Next, the core was not uniformly degraded – rather, there were places which showed more degradation than others.
Potential applications and future improvements
This principle opens the door to a whole array of treatments that were previously unavailable to children and provides the hope of improving upon procedures that tend to take their childhoods away while helping them. Potential applications exist for esophageal and intestinal atresias – conditions where the esophagus or the small intestine is constricted or not wide enough for the ingested food to pass through. Another potential application is for the surgical treatment of various conditions like prognathism and mandibular hyperplasia.
The prototype showed that in the presence of polymer core degradation, normal tissue growth was observed, where the absence of core degradation was associated with significant growth restriction. The use of a different braid material that induced a less pronounced fibrous tissue response could also facilitate ongoing polymer degradation and long-term device elongation. Alternative core shapes would increase the polymer’s surface area-to-volume ratio and could enhance the degradation. Potential modification to the device concept involves a core made of several distinct layers, each composed of a unique polymer that possesses a distinct degradation profile. An additional device modification could include light-triggered cleavable bonds in the core so that accelerated degradation could be triggered by external light. There are many potential improvements that could be done to the prototype, but its effect is already immense and its future promising.
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