Researchers at the University of Minnesota have developed a tissue-engineered heart valve replacement that can grow within a patient. The breakthrough could allow children with congenital heart defects to avoid repeated surgeries to replace heart valves that they have outgrown.
To create the valves, the researchers cultured donor cells in a fibrin gel within a bioreactor, allowing them to deposit a collagen matrix. They then removed the donor cells from the valve constructs before implanting them into lambs, where endogenous cells populated the valves and enabled them to grow.
At present, children with heart defects who require a heart valve replacement typically receive one made using animal tissues that have been chemically treated. Such valves can malfunction because of calcification and cause significant inconvenience for their recipients as they don’t grow along with the heart. This means that a child may undergo as many as five open-heart surgeries to replace the valve.
This latest technology has the potential to change this status quo. The researchers created new valves using donor cells that they seeded into a fibrin gel. They then cultured cells with growth nutrients in a bioreactor for a prolonged period, during which time the cells deposited a collagen matrix.
Using a detergent, the researchers then removed the cells from the collagen construct, leaving an acellular tubular material that does not provoke an immune reaction. Fashioning the tubes into a closed ring with leaflets, the team created a heart valve replacement.
Here’s a very short video showing the valve being repeatedly activated:
So far, the researchers have tested their technology in lambs. When implanted into the pulmonary artery, the valves became populated by cells from the lamb, and grew over the space of one year to become the same size as a physiologically normal valve.
“We knew from previous studies that the engineered tubes have the capacity to regenerate and grow in a growing lamb model, but the biggest challenge was how to maintain leaflet function in a growing valved conduit that goes through 40 million cycles in a year,” said Zeeshan Syedain, a researcher involved in the study. “When we saw how well the valves functioned for an entire year from young lamb to adult sheep, it was very exciting.”
Here’s an echocardiogram of the valve after implantation into a sheep:
“This is a huge step forward in pediatric heart research,” said Robert Tranquillo, another researcher involved in the study. “This is the first demonstration that a valve implanted into a large animal model, in our case a lamb, can grow with the animal into adulthood. We have a way to go yet, but this puts us much farther down the path to future clinical trials in children. We are excited and optimistic about the possibility of this actually becoming a reality in years to come.”
Study in Science Translational Medicine: Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs