A breakthrough in the manufacture of synthetic blood vessels has raised hopes that children born with serious heart defects could be treated in a single operation instead of multiple rounds of open heart surgery.

The landmark work comes from researchers in the US who made synthetic arteries that grow when they are implanted in the body, unlike the standard tissue grafts which are now used to correct faulty blood vessels.



Many children who are born with heart defects face a series of major operations over the course of their lives because the implants - known as conduits - that are used to replace their malformed blood vessels, do not grow in line with their heart and the rest of the body.



“A child might have five open heart surgeries for these conduits to be resized as they grow, and that can mean incredible anguish for the patient and family,” said Robert Tranquillo who led the research at the University of Minnesota.



Tranquillo’s synthetic blood vessels are made from gels seeded with living cells called fibroblasts. The cells churn out the stretchy collagen web that gives skin its strength. To form the gels into arteries or veins, they are wrapped around little rods and grown in a “bioreactor” that provides the cells with all the warmth, exercise and nutrients they need to grow.



Before the synthetic blood vessels can be implanted they are washed in a detergent to strip out all of the living cells. These would otherwise cause an immune reaction in the recipient. The process leaves a flexible collagen tube that can be stored in a fridge until it is needed for a patient’s operation.



To test the lab-made blood vessels, the US team implanted them into three young lambs. In the operations, the synthetic vessels replaced sections of pulmonary artery which carries oxygen-depleted blood from the heart to the lungs.



Ultrasound images taken over the next 50 weeks showed that the artificial blood vessels grew at a normal rate as the animals aged. Later, when the scientists inspected the implants under a microscope, they found that like natural blood vessels, the synthetic ones had an inner lining and contained smooth muscle cells and elastin, a highly elastic protein that allows blood vessels expand and contract.



“The amazing thing is that the recipient lamb cells repopulate our matrix and it physically grows. There are many suggestions that we are getting normal growth,” Tranquillo told the Guardian. So far the team has made synthetic blood vessels ranging from 2mm to 24mm wide to suit hearts from babies to adults.



The approach has advantages over another experimental technique that grows new blood vessels from a patient’s own cells. These implants, known as autologous grafts, are more costly and time consuming, because they have to be grown for each individual patient. In contrast, Tranquillo says one skin biopsy holds enough cells to make thousands of synthetic blood vessels that can be stored until needed. And because the living cells are removed first, the vessels can be implanted in any patient without inducing an immune reaction.



While the work is impressive, it is not yet ready for humans. Tranquillo said his team would discuss the results, published in Nature Communications, with cardiologists and the US Food and Drug Administration to decide what further lab work was needed before considering a clinical trial in humans. The team is separately working on more complex blood vessels that incorporate valves.



Paul de Bank, a tissue engineer at Bath University, said the ability of a graft to grow with a patient offered the possibility of a “one-time procedure”, rather than the patient requiring multiple surgical revisions.” This is understandably very attractive from a clinical point of view, with the added benefit that the graft in this study is acellular. This means that it could be an off-the-shelf product, available to surgeons as and when required and not affected by the financial and timing constraints of an autologous, cell-containing graft,” he said.

But he added that while the results from Tranquillo’s animal studies were promising, larger studies were needed to learn whether the vessels could be used in people.



Peter Weissberg, medical director at the British Heart Foundation (BHF), said that after decades of research, most children with congenital heart disease now survive into childhood. “But sadly, they still often have to undergo multiple operations at a young age as their hearts grow, which can be incredibly distressing for the child and their family.



“This exciting research indicates that it may be possible to create blood vessels in the laboratory that will grow as the heart grows. This could reduce the need for these operations and potentially improve the quality of life for children with congenital heart disease.



“BHF-funded researchers in Bristol are working on a similar approach in which the baby’s own cells are used to create ‘living’ blood vessels that could one day be used to repair their congenital defects,” Weissberg said. “The BHF’s Mending Broken Hearts Appeal is aimed at accelerating this research so that babies born with congenital heart defects in the future can look forward to a healthy life after a single operation.”

