University of Minnesota biomedical engineers have developed artificial blood vessels that, after implantation in young lambs, have proven capable of growth within the recipient. If transplantable in humans, these new vessel grafts could prevent the need for repeated surgeries in some children with congenital heart defects.

In the study, Biomedical Engineering Professor Robert Tranquillo and colleagues generated vessel-like tubes in the lab from a post-natal donor’s skin cells and then removed the cells to minimize the chance of rejection. This also meant the vessels could be stored and implanted when needed, without the need for customized cell growth of the recipient. When implanted in a lamb, the tube was then repopulated by the recipient’s own cells, allowing it to grow.

Researchers are working to create an off-the-shelf material that can be implanted in patients and grow in the body. Image credit: University of Minnesota. “This might be the first time we have an ‘off-the-shelf’ material that doctors can implant in a patient and [grow] in the body,” Tranquillo says. “In the future, this could potentially mean one surgery instead of five or more surgeries before adulthood.”

To develop the material for the study, researchers combined, in the form of a tube, sheep skin cells in a gelatin-like substance called fibrin and then rhythmically pumped in nutrients necessary for cell growth for up to five weeks using a bioreactor. The pumping bioreactor provided both nutrients and “exercise” to strengthen and stiffen the tube. The bioreactor was a key component in developing a bioartificial vessel stronger than a native artery so it wouldn’t burst in the patient.

The researchers then used special detergents to wash away all the sheep cells, leaving behind a cell-free matrix that does not cause immune reaction when implanted. When the vessel graft replaced a part of the pulmonary artery in three lambs at five weeks of age, the implanted vessels were soon populated by the lambs’ own cells, causing the vessel to bend its shape and grow together with the recipient until adulthood.

“What’s important is that when the graft was implanted in the sheep, the cells repopulated the blood vessel tube matrix,” Tranquillo says. “If the cells don’t repopulate the graft, the vessel can’t grow. This is the perfect marriage between tissue engineering and regenerative medicine, where tissue is grown in the lab and then, after implanting the decellularized tissue, the natural processes of the recipient’s body make it a living tissue again.”

At 50 weeks of age, the sheep’s blood vessel graft had increased 56% in diameter, and the amount of blood that could be pumped through the vessel increased 216%. The collagen protein also had increased 465%, proving that the vessel had not merely stretched, but had actually grown. No adverse effects such as clotting, vessel narrowing or calcification were observed.

Tranquillo says the next step is to determine the feasibility of gaining approval from the Food and Drug Administration for human clinical trials.