Bioengineered blood vessel grafts grow in animals

The engineered blood vessel (white). An “off-the-shelf” implant that can grow in the body could prevent the need for repeated surgeries in children with congenital heart defects.Tranquillo lab/University of Minnesota

Congenital heart problems are the most common type of birth defect, affecting 8 out of 1,000 newborns. While some defects are minor and don’t require any treatment, others need surgery to reconstruct or replace a faulty blood vessel or heart valve.

Current repair procedures include the use of synthetic materials or bovine vein grafts. These materials have several limitations. They can cause inflammation, and they’re unable to grow and change as the recipient develops. As a result, some children with heart defects may need numerous surgeries during their lifetimes.

A team led by Dr. Robert Tranquillo of the University of Minnesota set out to develop an “off-the-shelf” graft—one that could be stored and used as is—that could also grow with the body. The research was supported by NIH’s National Center for Advancing Translational Sciences (NCATS) and National Heart, Lung, and Blood Institute (NHLBI). Results were published online on September 27, 2016, in Nature Communications.

The scientists grew sheep skin cells (fibroblasts) in a fibrin gel enclosed within a tubular glass mold for 2 weeks. The developing tissue was transferred to a bioreactor vessel and grown for 5 more weeks. During this time, the tissue tube was stretched using gentle waves of pressure to stimulate the cells to convert the soft fibrin gel into a tissue as strong as a native artery. The skin cells were then removed with detergents, leaving a “decellularized” structure made mainly of collagen. Such a structure wouldn’t trigger an immune response and could be easily stored.

The team surgically implanted the engineered tubes to replace part of the pulmonary arteries of three 2-month-old lambs. This large artery carries blood from the right side of the heart to the lungs, and is involved in several types of congenital heart defects.

The researchers monitored the grafts and heart function over time with ultrasound. As the animals grew normally into healthy adults, the grafts increased in diameter, length, and volume. Their diameters matched that of the adjacent artery, so that blood flow wasn’t affected. The grafts became curved in a pattern similar to a normal pulmonary artery. The implants showed no signs of calcification, balloon-like bulges (aneurysms), or narrowing (stenosis). 

The scientists analyzed the grafts when the animals were 50-week-old adults. The grafts had increased in diameter from 16 mm to more than 24 mm and in length from 16-19 mm to 37-41 mm. They contained endothelial and smooth muscle cells, collagen and elastin, and had mechanical properties similar to control arteries. There were no signs of any adverse immune response.

“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 makes it a living tissue again,” Tranquillo says. “In the future, this could potentially mean 1 surgery instead of 5 surgeries that some children with heart defects have before adulthood.”

—by Carol Torgan, Ph.D.