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Our heart has four valves. These valves ensure that blood flows in the right direction. When a valve no longer works properly, it needs to be repaired or replaced.

Currently, there are two types of artificial heart valves. The first type is made from animal tissue, from pigs or cows. This type wears out over time. The second type is made from metal. This type attracts blood clots, which means the patient has to take blood thinners for life. In addition, neither type grows along with a child as they get older. That makes them unsuitable for young patients.

A living heart valve as the goal

Researchers are working on a new technique: tissue engineering. The idea is to create a heart valve made from the patient's own cells and tissue. Such a valve would last a lifetime, would not attract blood clots, and could grow along with a child.

In one approach within this technique, a temporary framework, called a scaffold, is placed directly in the heart at the location where the valve needs to function. This scaffold is made from smart, biodegradable plastic. The body responds to this material as if it is healing a wound: it slowly breaks down the scaffold while simultaneously building a new, real heart valve. The resulting valve is then entirely the patient's own.

The problem: calcium deposits in the scaffold

Many studies have already been done on this technique, both in the laboratory and in animals. Those studies showed promising results. But there was also a problem that was not yet well understood: small calcium deposits sometimes form in the scaffolds. Calcium does not belong in a heart valve. This phenomenon is called calcification. Van der Valk investigated where this calcium comes from and how the process unfolds.

Key findings from the research

Van der Valk first looked at all the animal studies that had previously been done with this type of scaffold. She found that only half of those studies had even looked at calcification. In the studies that did, calcification was found in one third of the animals. However, the calcification was less severe than in current artificial heart valves made from animal tissue.

In a closer analysis of two studies, she identified two types of calcification. Large calcium deposits resembled the kind of calcium found in known heart valve diseases. But small, microscopic calcium particles turned out to form through a process that was not yet understood. That was a new finding.

The immune response plays a key role

Van der Valk also observed how new tissue grows into the scaffold. This started at the point where the valve attaches to the heart and spread from there toward the free end of the valve. That growth was driven by the body's immune response.

To study this more closely, she developed new laboratory models. These allowed her to study calcification in scaffolds outside the body. She found that calcification in scaffolds follows a different process than in current artificial heart valves made from animal tissue. Just like tissue formation, calcification also turned out to be closely linked to the body's immune response.

Guidelines for future research

Van der Valk also proposed standards for testing TEHVs, short for Tissue Engineered Heart Valves. Such standards make it easier for scientists and physicians around the world to compare each other's results and work together to improve the technique.

A step closer to use in patients

The research showed that calcification remains a challenge for the use of these scaffolds in real patients. But the work also provided new tools and insights to better understand this problem. Using new laboratory models and techniques, it was demonstrated that the body's immune response not only stimulates new tissue formation but can also trigger calcification.

With this knowledge, researchers can develop and test materials in the future that prevent calcification. That brings a living, growing heart valve, one that lasts a patient's lifetime, one step closer.

This research was conducted within ICMS (Institute for Complex Molecular Systems) at Eindhoven University of Technology, in the research group Cell-Matrix Interactions in Cardiovascular Tissue Regeneration, led by Professor Carlijn Bouten. The research was funded by the program 'Materials Driven Regeneration', funded by the Netherlands Organization for Scientific Research (NWO, 024.003.013).

This dissertation is under embargo until June 9, 2027.