Pig intestine yields versatile tissue graft.

First, there were chitlins. Then, butchers started packaging sausage in the strong but thin casing of pig intestine. Now, tissue engineers are fashioning the proverbial silk purse out of a sow's gut by using a diaphanous inner layer of pig intestine to make tissue grants for replacing worn-out blood vessels, ligaments and bladders. Their aim: an off-the-shelf graft that can serve as spare parts for any patient, regardless of tissue type.

Veterinarian-physician Stephen F. Badylak and his colleagues at Purdue University in West Lafayette, Ind., have isolated a tissue film the thickness of two human hairs that they can transplant successfully into many other species, including dogs and moneys. Badylak told a symposium on tissue engineering last week that his team has transplanted the material into more than 600 animals of various species without any signs of immune rejection. The session was part of the Keystone (Colo.) Symposia on Molecular and Cellular Biology.

The researchers call the material SIS, for small intestinal mucosa. Much like the film of jelly between two layers of a jellyroll cake, SIS lies between the outer, muscular intestinal surface and the layer of finger-like villi lining the intenstine's inner wall. It consists mainly of collagen, the connective tissue that holds most organs together.

Badylak and his colleagues have a cheap and plantiful supply of SIS from their local slaughterhouse. "It's very similar to what they use for sausage casings," he says. After meticulously scraping off the inner and outer intestinal layers, the researchers place the resulting SIS in a bottle of antibiotic-laced saline solution and store it in a refrigerator, where it keeps for more than a month.

Because of SIS' ability to resist blood clots, the Purdue group first used it in dogs to replace the aorta, the largest artery in most animals. Remarkably, they found that the opaque-white material dissolved over two months and was replaced by the dogs' own blood vessel tissue, a phenomenon that tissue engineers call remodeling. Several of the dogs have lived four or five years since their transplants and have aortas indistinguishable from those of nongrafted dogs, Badylak says.

Following the success of the aorta transplants, Badylak's group tested SIS in dogs as a replacement for the vena cava, the largest vein in most animals' bodies. Unlike arteries, which carry high-pressure blood away from the heart, veins carry blood under lower pressure toward the heart and do not require a layer of smooth muscle to give them extra strength. The SIS vena cava graft adapted to form muscle-less vein tissue, Badylak's group discovered.

Encouraged by SIS' potential, Badylak's team then used the material to replace canine knee ligaments and Achilles tendons. Within weeks, the SIS became fully developed ligament and tendon tissue, they found. Moreover, a tunnel drilled in the dogs' leg bones to accommodate the knee ligaments closed around and fused with the new tissue.

The group hopes to test SIS grants in humans "within a couple of years," Badylak says. He predicts that orthopedic applications will come first, because of the lack of an adequate number of donor ligaments and tendons from humans. He and his co-workers recently began testing injections of minced SIS as a means to shore up the muscles of leaky bladders. They also plan to see if SIS will promote would healing when used as a skin grant. However, Badylak says, "I don't want to oversell this material ... we still don't know how it works."

Eugene Bell, a biologist at the Massachusetts Institute of Technology in Cambridge, calls SIS "extremely promising" as a universal tissue graft. "We are just beginning to probe the regenerative capacities of the human organism," he asserts. Synthetic materials have been "singularly ineffective" as tissue replacements, he says, because they do not serve as templates for the host to regenerate his or her own tissue and are sometimes subject to immune-system attack.