Researchers grow heart valves that are better than current animal derivatives
Researchers from the College of Science and Engineering and the Medical School, University of Minnesota Twin Cities, US, have created heart valves that were capable of lasting growth when implanted in lamb models. The valves also showed reduced calcification and improved blood flow function compared to animal-derived valves currently used when tested in the same growing lamb model.
According to the researchers, if confirmed in humans, these new heart valves could prevent the need for repeated valve replacement surgeries especially in thousands of children born each year with congenital heart defects. The valves can also be stored for at least six months, which means they could provide surgeons with an “off the shelf” option for treatment.
“This is a huge step forward in pediatric heart research,” said Robert Tranquillo, a professor in the university’s Departments of Biomedical Engineering and the Department of Chemical Engineering and Materials Science.
“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.”
The only accepted options for children with heart defects are valves made from chemically treated animal tissues that often become dysfunctional due to calcification and require replacement because they don’t grow with the child. These children will often need to endure up to five (or more) open heart surgeries until a mechanical valve is implanted in adulthood. This requires them to take blood thinners the rest of their lives.
“If we can get these valves approved someday for children, it would have such a big impact on the children who suffer from heart defects and their families who have to deal with the immense stress of multiple surgeries,” Tranquillo said. “We could potentially reduce the number of surgeries these children would have to endure from five to one. That’s the dream.”
In this study, Tranquillo and his colleagues used a hybrid of tissue engineering and regenerative medicine to create the growing heart valves. Over an eight-week period, they used a specialised tissue engineering technique they previously developed to generate vessel-like tubes in the lab from a post-natal donor’s skin cells. To develop the tubes, researchers combined the donor sheep skin cells in a gelatin-like material, called fibrin, in the form of a tube and then provided nutrients necessary for cell growth using a bioreactor.
Finally, a cell-free collagenous matrix is formed that does not cause immune reaction when implanted. This means the tubes can be stored and implanted without requiring customised growth using the recipient’s cells.
After the tubes were sewn together replicate a structure similar to a heart valve, they were implanted into the pulmonary artery of three lambs. After 52 weeks, the valve regenerated as its matrix became populated by cells from the recipient lamb, and the diameter increased from 19 mm to a physiologically normal valve about 25 mm.
The researchers also noted a 17 to 34% increase in the length of the valve leaflets as measured from ultrasound images. In addition, researchers showed that the tri-tube valves worked better than current animal-derived valves with almost none of the calcification or blood clotting that the other valves showed after being implanted in lambs of the same age.
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