Tissue Engineered Blood Vessels that Respond to Changing Blood Flow Have Potential for Use in Heart Bypass Surgery

BUFFALO, N.Y. -- Researchers at the University at Buffalo have developed a process in which cells are used to construct new blood vessels, opening the door to growing new blood vessels for procedures like coronary bypass surgery, according to a paper published online on Oct. 14 in the American Journal of Physiology -- Heart and Circulatory Physiology.

The small-diameter tissue engineered blood vessels (TEVs), developed and implanted in sheep, exhibited the strength and resiliency necessary for implantation after just two weeks in culture, to date the shortest development time for artificial vessels that have functioned successfully.

The TEVs functioned well in vivo for 15 weeks after implantation.

The UB researchers constructed the vessels by embedding vascular smooth-muscle cells isolated from sheep umbilical cords into fibrin, the essential clotting ingredient in blood. The fibrin gel matrix then was shaped into cylinders; after only two weeks, the tissue thinned down to approximately half a millimeter and they could then be implanted.

A patent application has been filed on the novel, tissue-engineered vascular vessel and the method for making it.

"We have shown that fibrin-based vessels can be implanted in vivo, remain patent and support blood flow rates for 15 weeks," said Stelios Andreadis, Ph.D., associate professor of chemical and biological engineering in the UB School of Engineering and Applied Sciences. He was co-author on the paper with Daniel D. Swartz, Ph.D., research assistant professor, and James A. Russell, Ph.D., professor, both in the UB Department of Physiology and Biophysics in the School of Medicine and Biomedical Sciences.

The tissue engineered blood vessels exhibited blood flow rates and reactivity similar to those of native vessels.

"It's not a stretch to extrapolate that these TEVs could remain functional in the long term because the animals presented no adverse effects," said Andreadis.

Even more critical, the scientists say, the TEVs performed like native vessels 15 weeks after implantation, when the animals used in the research were sacrificed. They exhibited excellent "remodeling," producing collagen and elastin, and had increased their mechanical strength by more than a factor of three.

"These are the first tissue engineered vessels to show long-term viability without clotting -- a key problem with small diameter vessels -- and with no adverse effects observed from the material we used," said Andreadis.

"Before implantation, the inner walls of these TEVs are coated with endothelial cells to mimic the composition of native tissue and prevent thrombosis," Andreadis said.

After implantation, he noted, the fibrin gel was completely undetectable, an important outcome since some materials in other systems have degraded into toxic byproducts.

The TEVs also exhibited not just mechanical strength, but the critical ability that native vessels have to constrict or dilate in response to their environment.

"We put our TEVs through rigorous testing," he added, "and we found that they are very reactive. We have developed vessels that dilate or constrict mechanically in response to chemical compounds. That's how native vessels adapt to changing flow rate."

Because of this property, the vessels may have additional applications as model systems for studying how mechanical forces act on the blood vessel wall.

They also may have application as toxicological models for in vitro testing of how vasoconstricting or vasodilating drugs affect blood vessels, Andreadis added.

The research was supported by grants from UB's Interdisciplinary Research and Creative Activities Fund and by the Women's and Children's Hospital of Buffalo.

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