Medical Marvels of the Pig
Doctors are treating an unusually wide array of serious ailments, from torn shoulders to open skin sores to leaky bladders, with a new jack-of-all-trades material from an unlikely source: pig intestine.
Some doctors marvel at the material’s ability to perform a rare feat of bioengineering. Inserted into a wound or injury, it prompts the body to grow blood vessels, skin, tendons, muscle fibers or other tissues just where they are needed. Then it disappears.
Exactly how it works puzzles scientists, though they have clues. The lining of the small intestine, animal and human alike, replaces itself every five days--faster than any other tissue--and this knack for renewal may help the material revive damaged tissues when implanted elsewhere in the body.
It is known as SIS, for small intestinal submucosa, referring to the middle layer of the intestinal wall from which it is extracted. SIS is processed into strips and also into sheets, which look like wax paper.
The material consists of a matrix of collagen polymers--a basic ingredient of cartilage, tendons and ligaments--as well as proteins that appear to spur cell growth, said the lead inventor, Dr. Stephen Badylak of Purdue University.
The Food and Drug Administration recently granted approval to two companies to market it. DePuy Orthopedics sells SIS strips for repairing injured joints. Cook Biotech sells sheets and straps to heal wounds and patch organs. Like Purdue, both companies are in Indiana, where there are as many hogs as people.
Dr. Gary Fanton, a surgeon in Menlo Park, Calif., specializing in sports injuries, has stitched SIS strips into injured shoulders. He and his colleagues have treated 40 to 50 patients with worn rotator cuffs--tendons that help hold the joint in place. Presumably, he said, SIS material lashed to a damaged tendon prompted new tissue to grow there.
“Until SIS came along, we had no way of reinforcing or enhancing the thickness of that tendon,” said Fanton, who is a team physician for Stanford University and the San Francisco 49ers football team.
Previously, surgeons used synthetic fabrics to repair such sundered joints, but he said either the body eventually reacted to that foreign material, causing harmful inflammation, or the material simply broke down. So far, they’ve had “very good results” with SIS, he said, with no adverse effects, such as immune rejection.
Dr. Alvin Rutner, a Mountain View, Calif., urologist, and his colleagues have used SIS fibers to treat a type of incontinence in 50 women. Anchored to pelvis bones, the fibers secure the sagging bladder in place and have helped restore control over urine flow in 49 of the patients, he said.
He added that the SIS caused no infections and did not prompt the immune system to reject it. And in follow-up studies on several patients, ultrasound checks showed the SIS material had disappeared after several months, said Rutner, who has been a consultant to Cook Biotech.
Celebrating the Small Intestine
The success of SIS spotlights the vitality of the small intestine, an organ whose glories are seldom celebrated. The complex process by which the inner lining perpetually renews itself is largely shaped by the middle, collagen-rich layer from which SIS is derived. It provides not only the scaffolding upon which the reconstruction occurs but also nutrients and proteins that spur the activity.
The key to the material’s effectiveness as a medical treatment is related to its role in intestinal rejuvenation. Placed in a wound, it recruits the body to send fibroblast cells to the site. These cells produce collagen and other substances that grow into arteries and tendons. New blood vessels branch into the area, supplying nutrients and carrying away waste products--including, eventually, the dissolving SIS itself.
Perhaps not surprisingly for a material that shares some properties with sausage casing, the first attempts to use it as a medical device little more than a decade ago were met with jeers, Badylak said.
“But . . . we shouldn’t be surprised that it’s effective, because the intestine is a tissue that needs good wound-healing properties,” he said. He said the small intestine takes a beating from viruses, abrasive chemicals and digestive enzymes.
In his first experiment, on a dog, Badylak replaced the major artery connected to the heart with a slender tube fashioned out of the porcine tissue. Doctors were looking for a better artificial blood vessel for electric pumps that assist failing human hearts, because the synthetic vessels then in use could trigger blood clots.
The dog lived another eight years before dying of natural causes, he said. And dissection showed that a new stretch of aorta had grown back where the SIS tube was placed. Badylak--who holds doctoral degrees in medicine, veterinary medicine and pharmacology--said he had never heard of such a thing.
More than 5,000 SIS experiments have been done so far, with 500 people receiving SIS implants of one kind or another, he said.
SIS is one of several materials for repairing wounds or replacing body parts. Some are synthetic fibers or fabrics, such as Gore-Tex. Some skin and tissue grafts come from cadavers. Other products are composites of living cells and synthetic materials.
But these materials tend to have drawbacks, as proponents of SIS point out. Synthetic materials often provoke the body to reject them, so patients must take anti-rejection drugs. Cadaver tissues cannot always be completely sterilized before use, raising concern that they may carry infectious microbes.
In contrast, SIS escapes the immune system’s notice, evidently because it lacks whole cells or cellular components that betray bodily invaders as foreign. And SIS withstands sterilization, accomplished by bombarding the material with radiation, said Mark Bleyer, Cook Biotech’s executive vice president.
Not All Applications Have Been Successful
Researchers and doctors working with SIS say it is too soon to tell to what extent it may replace existing wound-treating materials. And not all applications have panned out. Early hopes that it would replace ligaments such as those in the knee have been dashed, Fanton said. It is not strong enough to take such strain, regardless of whether it prompted regrowth of the ligaments, he said.
Nevertheless, anything that so clearly promotes healing stirs interest in medical circles. Badylak said he was most excited by the observation that the new tissues generated in response to SIS seem youthful, even in patients who are quite old.
That suggests to him that SIS spurs a healing response that people tend to lose as they get older. If scientists can figure out how the material prompts new, seemingly youthful tissue to grow, he said, “we’ll really have something.”
SIS can be used in a variety of forms. At left, Dr. Stephen Badylak, the lead inventor, displays a thin sheet. Below left, Rhonda Clarke, a researcher at DePuy Orthopedics, prepares a processed strip for packaging.
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Healing From the Gut
A new but rather low-tech material for treating wounds and injuries is derived from the middle layer of the pigs’ small intestines. Called SIS, for small intestinal submucosa, the processed material is a flexible, collagen-rich polymer. It can be fashioned into sheets, for patching internal wounds, or into straps, for reinforcing worn tendons like those in the shoulder.
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Source: Cook Biotech Inc.
