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But a tube is not a valve.
The site of most valve disorders in adults is the heart’s left ventricle, and Tranquillo and his students struggled to come up with a way to make a tricuspid valve similar to the one that fails most often in that high-pressure chamber.
Syedain, now a research associate and consultant, came through again. He found a 1996 patent for a “tubular heart valve” that is made from cow tissue. The tissue is stitched into a tube and placed around a frame that resembles a three-pronged crown.
Tranquillo’s researchers applied the idea to their tissue-engineered tubes. They expanded them to an internal diameter of 22 mm — about the size of a typical adult heart valve — and placed them around a frame they’d built. When they applied suction to the tube, the sides collapsed inward the way a balloon does when someone sucks out the air. When the flow reversed, the tube reopened. In other words, it functioned like a tricuspid valve. The U has patented the process.
“The metrics for this engineered heart valve are as good as any commercial valve,” Tranquillo said. “If it wasn’t for Zeeshan, I don’t know that we’d be having this conversation.”
Flexible and durable
Replacement heart valves, whether taken from pigs or constructed from cow tissue, work reasonably well for adults. But they have some drawbacks: They require anti-clotting medications and they wear out after 15 to 20 years. And because they cannot grow with the patient, they’re not well-suited for juveniles.
Tranquillo says his team’s tissue-engineered valves shouldn’t have those problems. But if they’re produced using skin cells from a donor, the patient would have to take immunosuppressants, which have undesirable side effects. That leaves two options. They could use a patient’s own cells to produce a valve — a process being pursued by the Mayo Clinic in Rochester, which is considering a collaboration with Tranquillo. Or they could kill the foreign cells, leaving a collagenous scaffold. In the latter case, a patient’s own cells would then attach to the valves, either in a bioreactor or after they’re implanted. Either way, the end result would be a living valve.
Tranquillo said the engineered arteries have become extensively “recellularized” just by being implanted in a patient.
“So it’s not something that’s like a piece of scar tissue,” Tranquillo said. “It seems to be regenerating.”
For now, Tranquillo’s lab team continues to refine the process in experiments with sheep. But eventually, he said, he hopes the U will commercialize and market the technology. They already have a “frameless” valve prototype that could be implanted in children if they can show that it grows after implantation into lambs.
Tranquillo beams as he considers the potential impact of his life’s work. “From one person’s donation of skin you could probably have enough cells to treat thousands of patients,” he said.
Dan Browning • 612-673-4493