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Construction 101: Building a better bypass graft

by Anissa Anderson Orr

Johnny Chen, MD, PhD

Johnny Chen, MD, PhD, has put on a builder’s cap to develop a better, stronger graft for heart bypass surgery. His challenge is to produce an artificial blood vessel with no synthetic material the body would reject. The graft also has to prevent dangerous blood clots that could block blood flow. Chen found the solution rooted in the basics of construction.

“We decided to use the carotid artery of a pig to build a scaffold completely free of any pig cells,” said Chen, a professor in the Michael E. DeBakey Department of Surgery and director of the Molecular Surgeon Research Center. “Our hypothesis is that once it is implanted in the human body, the scaffold will repopulate itself with human cells, eliminating the potential for rejection.”

Chen’s is one of 10 research teams in the United States charged by the National Institutes of Health to develop more durable bypass grafts. The need is great. More than half a million coronary bypass surgeries are performed every year, according to the American Heart Association. Current bypass grafts made from synthetic materials eventually fail. The most common method of bypass surgery uses a piece of a long vein from the patient’s leg. One end is sewn onto the aorta, while the other end is grafted to the coronary artery below the blocked area. Another technique uses an internal mammary artery. It is more durable than the vein.

“This is still an invasive surgery, and the graft only lasts about five years until it is blocked again,” Chen said. “Then we need to repeat the process and remove another vein.”

Funded by a $1.8 million grant from the NIH, Chen and his research team are investigating strategies using tissue engineering to create a new graft. Tissue engineering is an emerging field that regenerates or replaces damaged tissues with laboratory-grown parts such as bone, cartilage, blood vessels, and skin.

The studies are currently being conducted in heart models constructed in the laboratory and animal models.

To create the scaffold, Chen’s research team takes a carotid artery of a pig, and removes all the cells to only leave collagen and elastin. (A carotid artery extends through the neck and supplies blood to the brain and other organs in that area.)

“Among the species, collagen is pretty consistent, so it is not rejected,” Chen said.

The team then uses a process called covalent linkage to incorporate the blood thinner heparin into the scaffold, to prevent blood clots from forming inside the graft.

Chen "seeds" the scaffolds with human endothelial stem cells grown in culture, and then implants the scaffolds into the body of test animals. In another group of test animals, researchers implant another group of scaffolds that have not been seeded. The goal is to determine which group of grafts will repopulate with cells more quickly. So far, researchers have tested the graft in 30 animals for tissue reaction, and will follow 15 of the animals for two years to analyze graft performance.

“The vision behind our research here in the molecular surgery lab is to be clinically relevant,” Chen said. “There is an enormous clinical demand for an alternative to current bypass grafts.”

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