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People who need a heart valve replacement currently have two main options. Mechanical valves are durable, but they increase the risk of blood clots. As a result, patients must take blood-thinning medication for the rest of their lives.

Biological heart valves do not require lifelong blood thinners, but they tend to wear out over time. The material can degrade and become calcified, causing the valve to lose function. Younger patients are particularly affected because they are more likely to need additional valve replacements later in life.

Neither type of valve grows with the patient. For children, this often means repeated surgeries to replace the valve with a larger one as they grow.

A heart valve the body can rebuild itself

One promising alternative is known as in situ tissue engineering. In this approach, surgeons implant a temporary biodegradable structure, called a scaffold. The scaffold functions immediately as a heart valve while also serving as a framework for new tissue formation.

Once implanted, the scaffold attracts the patient鈥檚 own cells. These cells gradually replace the scaffold material and build new living heart valve tissue. In the future, this could lead to heart valves that grow with the patient and can repair themselves when damaged.

The success of this approach depends heavily on the body's initial response to the implant. That response is influenced by the scaffold material, its structure, the cells involved, and the surrounding blood flow. Because many of these processes are still poorly understood, Vetter's dissertation focused on both developing new valve designs and gaining a better understanding of how they interact with the body.

A synthetic heart valve inspired by nature

The first part of the research focused on developing a new synthetic heart valve. Many existing synthetic scaffolds are made from a single material and do not resemble the complex structure of a natural heart valve.

To address this, Vetter developed a three-layer scaffold that mimics the architecture of a native valve. This biomimetic design allowed the valve leaflets to move smoothly, close completely, and withstand the pressures generated by blood circulation.

In an initial animal study, the valve continued to function properly after implantation. The researchers also observed the growth of host cells into the material, an important step toward the formation of living tissue.

Bringing donor tissue to life

The second strategy used biological donor tissue. In this approach, heart valve tissue was treated to remove all original cells while preserving the natural structure of the tissue. This process is known as decellularization.

Although the remaining structure can guide new tissue formation, incoming cells often stay near the surface rather than spreading throughout the valve. As a result, the tissue does not fully develop into a living heart valve.

To overcome this limitation, Vetter developed a new technique using hydrogels, soft water-rich materials that can carry cells. The method allowed cells to be distributed evenly throughout the entire thickness of the valve leaflet.

In sheep studies, these biological valves continued to function for several weeks while retaining the introduced cells.

What happens immediately after implantation?

Although animal studies provide valuable information, they offer limited insight into what happens during the first hours and days after implantation. These early events are critical because they strongly influence how the valve develops over time.

To investigate this stage, Vetter established a new testing platform that simulated realistic blood flow conditions. Whole blood was pumped across different scaffold materials under pulsatile flow conditions that mimicked the natural heartbeat.

Only under these realistic conditions did clear differences between materials become visible. Synthetic scaffolds rapidly attracted neutrophils, the immune cells that are among the first to respond to injury or foreign materials. This response was much less pronounced in decellularized scaffolds.

The study also showed that surface structure had a greater impact on this early response than the chemical composition of the material itself. Neutrophils attached more readily to porous, fibrous surfaces, where they formed web-like DNA structures. These structures can activate other immune cells and promote inflammation.

The findings demonstrated that the design of a scaffold's surface plays a key role in shaping the body's earliest response to an implant.

Helping advance the next generation of heart valves

In addition to developing new valve technologies, Vetter initiated, together with Dewy van der Valk, an international expert consensus on the minimum requirements for testing and reporting regenerative heart valve studies.

These recommendations aim to improve consistency across studies and make research results easier to compare. Ultimately, this could accelerate the development of safe and effective regenerative heart valves for clinical use.

A step toward living heart valves

The studies in this dissertation provided new insights into the early interactions between blood, immune cells, and regenerative heart valve materials. They also resulted in two promising heart valve strategies: a synthetic three-layer valve and a biological valve in which cells can be introduced deep into the tissue.

The research showed that the surface structure of a scaffold is a key factor in determining the body's early response. This insight provides an important foundation for designing future generations of living heart valves.

In the long term, such valves could become an alternative to current prosthetic valves. For children in particular, a valve that grows with the patient could greatly reduce the need for repeated surgeries and significantly improve quality of life.

Please note: the dissertation is currently under embargo due to a patent application. The dissertation will be available as an open-access PDF from September 2, 2028.