“Have you got a new valve for me?” The 11-year-old boy is looking at Carlijn Bouten inquisitively. It is just one of those confrontational questions which the Professor of Regenerative Medicine has to deal with more often during meetings for cardiac patients. “Those are harrowing moments”, Bouten confirms. “You can’t promise anything, you can only emphasize that you are working on it at full throttle. Often even that is enough for them.” In her workroom the boy’s signature is hanging on the wall, together with those of other patients. “Apart from all kinds of brochures and the helpdesks, I keep them posted myself and I answer all their questions personally.”

Each body is formed from an egg cell and a sperm cell and grows by its own means into a complex, independent being. Scientists and physicians see opportunities in this fantastic property. Deploying smart biomaterials and their knowledge of molecular cell biology they want to help the body repair worn-out tissues and organs. Although regenerative medicine is still in its infancy, expectations are high, also among patients.

Loerakker focuses on the mechanical factors that influence the growth and remodeling of heart valves. “It is our goal to be able to control those processes in a smart way“, says Loerakker, “for instance by adjusting the design of the valve. In my group the emphasis lies on the development of computer models, but the link with experiments is essential. Our simulations have already led to a great improvement in valve functionality, of which the details will probably appear soon in a publication.”

How does it work that 'smart control’? “The computer models help us understand and predict how tissues will develop and adjust inside the body. Once those models work well for situations of which we know the outcome from experiments, we can start to carry out different simulations whereby we adjust the design of the valve and watch its effect on functionality and regeneration. If the model predicts that certain changes can lead to drastic improvements in regeneration - and we have seen a convincing example of this one time already - we can test by means of experiments whether that is actually the case.”

Comparing model predictions with experimental results is not simple, Loerakker adds. “A lot depends on the goal we want to achieve with a certain computer model. In most cases we try in particular to understand the physics involved in certain processes, and then we look especially at the main parameters of tissue organization, such as the organization of collagen fibers or cells, and we assess whether the main aspects of those correspond between the model and the experiment.”

Anthal Smits and his PhD candidates are trying to predict the immune reactions that occur when the synthetic valve has been inserted into a body. “At the time it was quite a big thing already to reverse the process”, Smits explains. “In the beginning we tried to grow the valve outside the body, but when it was inserted, the cells that were harvested in the lab did not react the way we had hoped. Therefore it was decided to place the synthetic valve without cells in the body. The immune reactions to that proved to be essential for starting the process whereby endogenous cells finally replace the valve with new tissue that was being made by the own body. In this process a very important role is played by macrophages, a specific type of white blood cells that were always regarded like a kind of blunt ‘workers’, and which are responsible for protecting the body against unwanted intruders like bacteria. We found out that these cells have yet another important feature; they attract other cells and thus have an organizational role in the recovery as well.”