Stanford, CA, USA. A method for reconnecting severed blood vessels appears to be an effective alternative to traditional procedures that use sutures, with potential application to lateral research on tissue generation, particularly on blood vessels less than 1 millimeter wide.

In animal studies, the medical scientists used a poloxamer gel and bioadhesive rather than a needle and thread to join together blood vessels, a procedure called vascular anastomosis.

The research team was led by microsurgeon Geoffrey Gurtner, MD. The lead authors of the study published in Nature Medicine were postdoctoral scholar Edward Chang, MD and surgery resident Michael Galvez, MD, of the Stanford University School of Medicine. Gurtner began thinking about alternatives to sutures back in 2002. "I was chief of microsurgery at Bellevue in New York City, and we had an infant — 10 to 12 months old — who had a finger amputated by the spinning wheel of an indoor exercise bike," he said. "We struggled with reattaching the digit because the blood vessels were so small — maybe half a millimeter."



French surgeon Alexis Carrel pioneered the reconnection of severed blood vessels and was awarded the 1912 Nobel Prize in Physiology or Medicine for advancing the technique.

These days, reconnection is mostly done the same way asa it was in Carrel's day — with sutures. However, they have a big drawback: sutures are difficult to use on blood vessels less than 1 millimeter wide.

Sutures are troublesome in other ways, too. They can lead to complications, such as intimal hyperplasia.

Cells respond to the trauma of the needle and thread by proliferating on the inside wall of the blood vessel, causing it to narrow at that point.

This increases the risk of a blood clot getting stuck and obstructing blood flow.

In addition, sutures may trigger an immune response, leading to inflamed tissue that also increases the risk of a blockage.The surgery took more than five hours but at the end surgeons were only able to get in three sutures. "Everything turned out OK in that case," Gurtner says, "but what struck me was how the whole paradigm of sewing with a needle and thread kind of falls apart at that level of smallness."

The new method could sidestep an even wider array of problems. [cf. Sidebar] "Ultimately, this has the potential to improve patient care by decreasing amputations, strokes and heart attacks while reducing health-care costs," the authors write in the study.

Earlier in his career, as Gurtner contemplated a better way of joining together blood vessels, he considered whether ice could be used to fill the lumen, the inner space of the blood vessel, to keep both ends open to their full diameter long enough to glue them together. Not feasible, he concluded. "Water turns to ice quite slowly and you would have to drop the temperature of the surgical site a lot — from 98.6 degrees to 32 degrees Fahrenheit," he said.

Shortly after arriving at Stanford in 2005, Gurtner approached fellow faculty member Gerald Fuller, PhD, professor of chemical engineering and the Fletcher Jones II Professor in the School of Engineering, about whether he knew of a substance that could be turned easily from a liquid to a solid and back to a liquid again, and that would also be safe to use in vascular surgery.

Fuller immediately suggested a Food and Drug Administration-approved thermoreversible poloxamer called Poloxamer 407. It is constructed of polymer blocks whose properties can be reversed by heating. Fuller teamed with Jayakumar Rajadas, PhD, director of the Stanford Biomaterials and Advanced Drug Delivery Laboratory, to modify the poloxamer so that it would become solid and elastic when heated above body temperature but dissolve harmlessly into the bloodstream when cooled.

The poloxamer then was used to distend both openings of a severed blood vessel, allowing researchers to glue them together precisely. The researchers used a simple halogen lamp to heat the gel. In tests on animals, the technique was found to be five times faster than the traditional hand-sewn method, according to the study. It also resulted in considerably less inflammation and scarring after two years.

The method even worked on extremely slim blood vessels — those only 0.2 mm wide — which would have been too tiny and delicate for sutures. "That's where it really shines," Gurtner said. Dermabond, a surgical sealant, was used to attach the ends of the blood vessels together.

Poloxamers have been used before as a vehicle for delivering drugs, including chemotherapeutics, vaccines and anti-viral therapies. Researchers have used Poloxamer 407 to occlude blood vessels in experimental animals for the purpose of evaluating the gel's safety and efficacy in so-called "beating heart surgery," in which certain vessels need to be temporarily blocked to improve visibility for the surgeons performing a coronary artery bypass.

Although other sutureless methods have been developed, they generally have not produced better outcomes, the authors said. "Often, the use of microclips, staples or magnets is itself traumatic to blood vessels leading to failure rates comparable to or higher than sutured anastomoses," they wrote.

"This is a novel approach to anastomosis that could play a valuable role in microvascular surgery," said Frank Sellke, MD, chief of cardiothoracic surgery at Brown University Medical Center and associate editor of the Journal of Thoracic and Cardiovascular Surgery, who was not involved in the study. "But it really needs to show that it holds up in clinical trials." The authors say further testing on large animals is needed before human trials can begin, but they note that all of the components used in the technique are already approved by the FDA. "This technology has the potential to progress rapidly from the 'bench to bedside,'" they write.

Gurtner said he believes the new technique could satisfy a huge unmet need and prove especially useful in minimally invasive surgeries, in which manipulating sutures takes on a whole new level of difficulty. Michael Longaker, MD, a co-author of the study, called the technique a "potential game-changer." Dr. Longaker is the Deane P. and Louise Mitchell Professor in the Stanford University School of Medicine.

"When you're bringing together hollow tubes, whether they're large structures, like the colon or the aorta, or a small structure, like a vein in the finger of a child, you're always worried about lining them up directly and effectively sealing them," Longaker said. "The technique that Dr. Gurtner has pioneered could allow surgeons to perform anastomosis more quickly and with improved precision."

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