For some years now, 18 children have been living across Europe, Asia and the US with an implanted, regenerative heart valve from the Eindhoven company Xeltis. Xeltis was founded thirteen years ago as a spin-off of Eindhoven University and is still based there, at Twice | hub Catalyst. In an interview with the magazine LABinsights, Martijn Cox, chief technology officer at Xeltis, talks about this strong example of supramolecular chemistry combined with regenerative medicine.
Library of materials
"Supramolecular chemistry allows us to develop a library of materials ranging from very stiff to very stretchy, from very fast to very slow-degradable. It is a much wider range of materials than you could achieve with ordinary chemistry," said Martijn Cox, chief technology officer and founder of the company in 2007. "The difference between supramolecular and ordinary polymers is that in supramolecular materials we use relatively short polymers that we can bond together like legoblocks using hydrogen bonds. This is a principle that is also used in nature, for example, in DNA. Water- and dust bridges are not that strong in themselves, but if you use a unit with several hydrogen bonds next to each other, it creates a strong and reversible connection. This makes these materials much stronger than you would expect on the basis of their molecular weight," Cox explains.
Xeltis uses this type of material to make heart valves and pieces of blood vessels that can be implanted in humans, says Cox. "We see that from day one, our implants function like the part of the body they replace. But they're porous at the same time, even if you can't see it with the human eye. As a result, the implanted blood vessels leak the first few minutes after implantation. But soon after that, the blood clots into the material and cells settle there. These include cells from surrounding tissue and cells circulating in the blood such as macrophages and fibroblasts. Actually, the same thing happens to tissue repair in a wound."
Over time, the plastic is completely filled and covered with the body's own tissue. "After about half a year, the plastic loses its strength by oxidation of certain bonds, so that it actually falls apart into chunks. Because it is then completely wrapped up in the new tissue, it can still take years before it has completely disappeared".
Functioning as a natural heart valve
What is left is a new heart valve or blood vessel from the body's own cells. "You'll always be able to tell it's not the same as a natural heart valve. The implanted heart valve, for example, is a little thicker and stiffer, but there are a lot of leftovers and essentially there is no difference in functioning," says Cox. "Like a natural heart valve, for example, there is a layer of cells that prevents clots from forming, and there are capillaries through the material and networks of proteins such as collagen and elastin".
Success with children
Xeltis initially focused on the development of heart valves for children. In a first clinical trial, twelve children from Europe and Asia have cremated Xeltis heart valves. The first results showed that there was still a slight complication, although the children did not notice much of it. After the heart valves were slightly modified, a new trial was started last year in six children from the US. So far, no complications have occurred, the researchers announced last February. "We hope that the body's own tissue will eventually grow with the children, but there is no evidence of this yet. But even if it doesn't, our heart valve is already an improvement over the current heart valves, which have to be replaced every few years because of wear and tear," says Cox.
High and low pressure
Meanwhile, Xeltis employees are busy developing other variants. While the first trial involved a low-pressure heart valve, the company is now also working on a high-pressure heart valve. More requirements are being placed on the material for this. In addition, work is being done on the development of a blood vessel for bypass surgery, so that it is no longer necessary to use a blood vessel from the patient's leg. It is expected that the first clinical trials with this will start at the end of 2020.
This article was published on 26 June 2020 in LABinsights.