Feb. 2, 2011 -- Scientists report that they have successfully grown and tested collagen-based tubes made from human donor tissue that can be used as blood vessel-like grafts in surgical procedures like coronary artery bypass and for creating vascular access points for patients who need kidney dialysis.
What’s more, the tissue-engineered grafts appear to be strong and pliable even after being refrigerated for a year, which means that they could be made ahead of time and kept at the hospital to be used when surgeons need them.
Other researchers have previously reported the ability to develop blood vessels from a patient’s own cells. That process was time consuming, however, requiring six to nine months for harvested cells to multiply and grow a sheet of tissue that could be rolled into a tube and implanted in the body.
"As the authors point out, there is a growing clinical need for replacement arteries and although tissue-engineered blood vessels have been used successfully in the clinic, there is still a need for "off-the-shelf" grafts that can perform as well as autologous small diameter blood vessels without the long production time associated with growing autologous cells to make a graft," says Marsha W. Rolle, PhD, assistant professor in the department of Biomedical Engineering at Worcester Polytechnic Institute in Worcester, Mass.
“I think this is an important study,” says Christopher Breuer, MD, a pediatric surgeon and director of tissue engineering at the Yale School of Medicine in New Haven, Conn., who was not involved in the research.
Bioengineering Blood Vessels
In the new procedure, reported in the Feb. 2 issue of Science Translational Medicine, researchers took smooth muscle cells from cadaver donors and seeded them onto mesh tubes made from the same strong, flexible material used to make dissolvable stitches.
The muscle cells then secreted proteins, primarily collagen, which formed a ring of biosynthetic tissue around the gradually dissolving scaffold, says study researcher Shannon L. M. Dahl, PhD, senior director of scientific operations for Humacyte.
As the collagen was growing, fluid was pumped through the tubes to subject them to stress similar to blood pressure pushing against vessel walls.
In a final step, researchers washed the collagen-based tubes to get rid of any remaining cells, which could trigger immune reactions in a recipient.
Researchers were able to make the tubes in two sizes. One was 6 millimeters, about the diameter of a standard drinking straw.
The others were 3 to 4 millimeters, about the size of cocktail straws.
They then tested the bioengineered blood vessels in two animal models. After six months, about 88% of the larger grafts were still open and trouble free in baboons. After one month, about 83% of the smaller vessels implanted around the hearts of dogs were still open.
The researchers have not yet tested the bioengineered vessels in humans, but Dahl says this study lays the foundation to do that.
“We estimate that 500,000 patients a year could potentially benefit,” says Dahl.
At least initially, Dahl thinks those will be patients who might need vessels to help reroute blood around blockages in the heart, or for whom doctors need to build an access point so that their blood can be cleaned for kidney dialysis.
“Tissue engineering is a very important frontier in medicine,” says study researcher Jeffrey H. Lawson, MD, a vascular surgeon at Duke University Medical Center.
“Replacing and understanding the complexity of the human body and its specific parts is really quite a challenge. Probably the first places where tissue engineering will become a reality will be in things like blood vessels, because they’re relatively straightforward structurally to construct, even though they’re still amazingly complex,” he says.
A New Way to Replace Blood Vessels
When blood vessels around the heart become dangerously congested with plaques, surgeons will reroute blood flow and bypass the blockages.
To do that, they may take blood vessels from other parts of the body, usually the leg or chest wall.
But there are cases when a person’s own blood vessels can’t be harvested. In those cases, a surgeon may reach for vessels made from synthetic polymers, like Teflon or Dacron, or for vessels donated from cadavers.
“It works OK, but it gets infected more than your natural tissue, and it tends to clot off,” Lawson says.
That’s where off-the-shelf bioengineered grafts may play a role.
In the 15 years that Humacyte’s grafts have been in development, Lawson says they have made enormous progress.
“Initially, the earliest prototypes were like sewing on wet toilet paper, which wasn’t very much fun as a surgeon. They would rip. So they’ve made remarkable progress and now it’s something that sews like a vein,” Lawson says.
Indeed, researchers made sure the tissue was strong enough to hold sutures by hanging weights from the tissues with surgical thread. They also inflated them with saline solution periodically to see how much pressure it would take to make them burst.
Until they can be proven to be reliably safe and effective, bioengineered blood vessels are most likely to be used as a last resort, but some doctors envision a day when they may become the norm.
“What’s so exciting about this technology to me is that maybe one day, even in people who have veins, we won’t have to use their veins,” says study researcher Alan P. Kypson, MD, a heart surgeon at the Brody School of Medicine at East Carolina University.
“We can just pull this stuff off the shelf. I don’t have to cut your legs open. You don’t have to complain of swelling and pain in your legs, you might avoid getting an infection, potentially, it will make your operation go quicker,” Kypson says. “It will change the way we might do this surgery in the future.”