Computer-Designed Heart Valves Operate Over Long Term

Computer-designed customized regenerative heart valve (University of Zurich)

10 May 2018. A European research team designed customized heart valves with computer models, which when tested in sheep continued to perform in most cases for a year following implantation. Researchers from University of Zurich and two other institutions describe the engineered heart valves and test results in yesterday’s issue of the journal Science Translational Medicine (paid subscription required).

The heart’s 4 valves keep blood flowing properly, but when they become impaired due to heart disease or high blood pressure, the valves fail to open and close properly, which disrupts blood flow throughout the body. In some cases, babies are born without properly functioning valves, a condition called congenital heart disease. A 2006 study estimates 5 million adults in the U.S. have malfunctioning heart valves, a condition that increases in risk as people age, with 1 in 100 newborns diagnosed with a congenital heart defect.

The team led by Simon Hoerstrup, a professor of regenerative medicine at University of Zurich in Switzerland, are seeking better options for replacement heart valves that in most cases today work for limited periods of time, even if they survive rejection by the immune system. In the case of infants and children with congenital heart defects, replacement valves today do not adapt as children grow. The European Union created an initiative called LifeValve to develop heart valves that function better and can adapt to children’s growth, which funded the research.

Hoerstrup — with colleagues from Zurich, Technical University Eindhoven in the Netherlands, and the Charité Berlin in Germany — devised a process that combines computer modeling with tissue engineering to design new heart valves that meet these conditions. The computer models use algorithms that simulate the growth and development of tissue-engineered heart valves replacing the originals. The models account for changes in the valves as they grow, stretch, and function over time, which as Hoerstrup notes in a university statement, “can optimize the design and composition of the regenerative heart valves and develop customized implants for use in therapy.”

The valves themselves are seeded with blood vessel cells, in this case from sheep in which the valves were tested. The blood vessel cells are arrayed on a polymer mesh framework specified in the computer model, then cultured in a bioreactor for 4 weeks. After culturing into tissue, living cells are removed from the valve, making the device less likely to provoke an immune response from the recipient. In addition, the replacement valves are designed for implantation with a catheter requiring minimally-invasive procedures instead of open-heart surgery.

The researchers tested the replacement heart valves with 11 sheep, and monitored the animals for 1 year. The results show the replacement valves functioned properly in 9 of the 11 cases over the 1 year test period. Factors affecting growth and change of the valves predicted in the computer models, such as alignment of collagen around the valves, were largely confirmed.

A major remaining challenge, says Hoerstrup, is to refine the process to enable the design of truly customized heart valves. “One of the biggest challenges for complex implants such as heart valves,” he notes, “is that each patient’s potential for regeneration is different. There is therefore no one-size-fits-all solution.”

The team plans to adapt this technology to create engineered blood vessels for children with congenital heart defects, in a related project at Zurich. Hoerstrup and several co-authors are holders of a patent assigned to Technical University Eindhoven covering a part of the technology in the study that controls the shape of heart valves as they develop in the lab.

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