Regenerative heart valves: from simulation to replacement

Every year, more than 250,000 patients worldwide receive heart valve implants. Children require repeated replacement surgery because their bodies are still growing, whereas the prosthetic heart valves are not. Regenerative heart valves can solve this problem. Until now, we have only been able to monitor how these living implants develop in the body after the fact. Thanks to computer models, these processes are now predictable.

In this MEDICA-tadefair.com interview, Professor Simon P. Hoerstrup explains how regenerative heart valves are made, describes why predicting their development in the body is so important, and reveals how this has now been achieved for the very first time.

Professor Hoerstrup, your research focuses on regenerative heart valves. What makes these prosthetic heart valves so unique? Why are they so important?

Prof. Simon P. Hoerstrup: Heart defects are present in nearly one percent of live births today. Approximately half of these children require a surgical procedure such as the replacement of a heart valve or blood vessel. That's a surprisingly large number. Artificial heart valves, which are also used in adults, are the current option for these tiny patients. The valves are made of plastic or animal tissue material. Although they generally work well, they have one major drawback when it comes to children: they are unable to grow as the child's body grows. This means children must undergo repeated replacement surgery until they reach full maturity to adapt the prosthesis to the growing body. Meanwhile, repeated surgeries can result in complications and sometimes even death. That's why we need implants that grow and ideally only require one-time surgery. This has prompted the research sector to use human cells and create heart valves or blood vessels in the laboratory – via so-called tissue engineering.

How does this process work?

Hoerstrup: We first take a polymer scaffold that's shaped as a heart valve. In the laboratory, human cells are then applied to this heart valve design where they subsequently proliferate on the scaffold, grow into it and finally create heart valve-like tissue. This happens because we place the construct in an artificial circulatory system where it is subject to the flow and pressure reminiscent of the heart. This stimulates the cells to create a new heart valve. The initial polymer scaffold then dissolves, creating a new human heart valve, which then strengthens inside the body and is capable of regeneration and growth.

As part of your EU-funded project called LifeValve, you have now successfully designed this type of heart valve on the computer. What prompted this?

Hoerstrup: In the past, one of the biggest challenges with regenerative heart valves has been that we were unable to accurately predict how our dynamic tissues would develop inside the body. This pertains to both growth and function. Oftentimes, we were only able to empirically observe in animal experiments that some heart valves shrank or didn't work optimally for example. This is problematic from a conceptual perspective if our goal is to use these regenerative heart valves for routine surgeries in humans in the future. We need to gain some control over the dynamic process - we call it remodeling - after implantation. For the first time ever, we have now succeeded in simulating these in vivo processes in a computer model and in adapting our heart valve design from the start to ensure optimal results. Previously, the field of tissue engineering had not experienced this kind of precision in this area.

For us, this has been such a great success because we now have a much better understanding of how our heart valves should be designed to function safely and reliably, allowing us to also adapt them to specific situations. For example, we know that patients with diabetes have a reduced potential for regeneration. We are now able to address this in the design of the heart valve. This allows us to not only achieve greater predictability and safety in terms of tissue engineering technology, but we can also customize the design of our implants.

You already explained the advantages but what are the limits of tissue engineering?

Hoerstrup: There will always be patients for whom regenerative implants are not an option because their organism doesn't have a sufficient ability to regenerate. An application would be too risky in these instance because the heart valves would not remodel optimally and their long-term function would be restricted. We would likely have to use conventional prosthetic options in this case to be safe. This is an example of where tissue engineering would reach its limits, though we are now able to better predict this event with the new computer simulations.

These new developments are primarily important to ensure the safety and reliability of our implants but they are also an important aspect when it comes to assessments made by regulatory authorities. The clinical adoption of a new technology requires us to show that we did everything in our power to guarantee the safety and proper functioning of the implants. This is another reason our computer simulations, which now introduce a higher level of control and predictability to the overall technology, are very relevant for the approval processes.

Speaking of "approval": What comes next?

Hoerstrup: Our next step is to apply this technology and support patients who suffer from a congenital heart defect. Since a heart valve features an intricate architecture, we will initially only engineer a tube, meaning a blood vessel via computer simulation for children with heart defects. This is less risky and less sophisticated from a technical perspective. If we achieve positive results with our computer model, our subsequent step would be a heart valve implantation.

What potential do you see in the field of bioengineering?

Hoerstrup: Aside from the cardiovascular field, attempts are made to implement tissue engineering solutions in essentially all organ and tissue systems. We can see a fundamental paradigm shift in this area. From our point of view, it is not just a trend but a sensible medical step to have regenerative or viable implants at our disposal. From a conceptual perspective, a prediction of how these implants develop once inside the body will also become increasingly important. For example, this enables you to predict the forces that act on a bone and project whether a patient’s weight or other characteristics necessitate a customized implant. If our continued experiments garner positive results and if we achieve better control thanks to our computer simulations, I would expect that this technology can and will be implemented in almost all bioengineering fields.