wrinkle fillers-are they safe

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WRINKLE-ERASING injections are a staple of the burgeoning trend of cosmetic nonsurgery — a practice pioneered by 30-somethings hoping to stave off fledgling wrinkles but fearful of looking unnatural and unwilling to take the time off work required for surgery. “Ultimately what people want is drive-through medicine,” says Dr. Kinney, a Los Angeles plastic surgeon and spokesperson for the American Society for Aesthetic Plastic Surgery, or ASAPS. “So any methods that aren’t surgical and have no downtime are favored.” Miami dermatologist Dr. Fredric Brandt partly attributes the boom in interest in plumping agents to the popularity of Botox. Botox is itself not a wrinkle filler — it’s a muscle-paralyzing toxin that causes food poisoning as well as furrow-free foreheads.

But with Botox injections spreading across the country like botulinum spores in a can of tainted chili, people are looking for ways to make the rest of their face match their line-free brows, says Brandt, who spends 80 percent of his day injecting patients with wrinkle treatments for $500 a pop and up. One of Brandt’s patients, 43-year-old Barbara, who asked that her last name not be used, began using bovine collagen, which is derived from cow skin, in and around her lips in her early 30s. As the Miami woman aged, she also started having collagen injected around her eyes, in her smile lines and on her chin every four to five months, plus regular Botox shots in her brow. “It’s all part of maintenance, like going to the gym, getting highlights or getting a manicure,” she says. “The injections are not a drastic change, they just make you look replenished, better and younger. If you care about the way you look you just have to keep doing it.” BEYOND COWS AND CADAVERS Bovine collagen, the granddaddy of wrinkle fillers, turns 20 in July and is still considered the “gold standard” by many doctors. It’s the No. 4 cosmetic procedure in the United States, with almost 600,000 performed in 2000, according to ASAPS. But its short duration — it disappears within three to six months — and its immunogenic nature — about 3 percent of the population are allergic to the substance — have sparked a hunt for a superior filler.

Dr. Kinney injects employee Marguerite Testu de Balincourt with collagen.

Earlier attempts in the 1990s expanded the plastic surgeon’s arsenal to include injections of tissue derived from human cadavers, implantable sheets of cadaver skin, implantable cylinders made of Gore-Tex and a technique for extracting fat from a patient’s own thighs or buttocks and then reinjecting it into facial creases. All have proved to be useful options but none has turned out to be a stealth weapon in the war of wrinkles — they last no longer than collagen, require incisions or lack the natural look or feel desired by patients. Now researchers have gone beyond cows and cadavers to develop new products. Doctors attending the annual ASAPS meeting in New York last month packed into sessions to learn about the new generation of wrinkle fillers in the pipeline, including a novel form of collagen, gels made from extracellular fluid and injectable plastic beads. All are expected to clear the Food and Drug Adminstration hurdles needed for approval, some within a year. Kinney says he expects the number of filler options to double in the United States within the next five years. “The results will get better, more natural looking, longer-lasting, with fewer risks,” he predicts. BIRTH OF A NEW COLLAGEN Last month, McGhan Medical Corp., the maker of injectable bovine collagen, applied for FDA approval of a new source of collagen: newborn foreskin. The company has isolated fibroblasts — collagen-producing cells — from the foreskin left over after circumcision. The cells are replicated in a culture, where they are primed to pump out collagen.

“Cells from an infant will grow in tissue culture for many more generations than those from older people so it’s a big advantage,” says Ray Duhamel, vice president for regulatory and clinical affairs for McGhan. “And this is the most benign way to obtain cells from a young person — the foreskin is usually discarded so it’s readily available. ” The foreskin-derived collagen is expected to last the same amount of time as bovine collagen so its duration isn’t its selling point. The advantage is that since the new source is human-based it avoids bovine collagen’s allergy risk. With bovine collagen, a prospective patient must take a skin sensitivity test on the forearm, then wait four weeks for the results. With the new human collagen no such test will be required. Plus, with bovine collagen, even if the sensitivity test comes back negative, there’s about a 1 percent chance of developing an allergy after several treatments — which can mean redness and inflammation around the area for months, and even the formation of cyst-like scars.

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Brandt’s patient Barbara, for example, had been receiving bovine collagen injections for nearly 10 years without problems until after her first pregnancy, when the areas where the collagen was injected became temporarily swollen. Brandt attributed the late-onset allergy to hormonal changes during pregnancy. So he switched Barbara to Dermalogen — an injectable filler derived from donated human cadaver skin. Unlike bovine collagen, Dermalogen contains no anesthetic, so Barbara has found the shots more painful. Brandt says the new foreskin collagen will be a good option for patients like Barbara because it will be mixed with lidocaine. In contrast, the other fillers of human origin — Dermalogen, Cymetra, Fascian, AlloDerm and Dermaplant — which all come from cadaver tissue, contain no anesthetic. McGhan is preparing to launch its human collagen products — CosmoDerm, for fine and moderate lines, and Cosmoplast, for deep wrinkles and folds — this fall. TINY BEADS The next filler expected to gain FDA approval is Artecoll, a popular product in Europe since 1989. The injectable solution, which has been used by more than 150,000 people worldwide, consists of microscopic plastic beads suspended in bovine collagen. The plastic has been used in bone cement and in other medical applications for years, says Dr. Stefan Lemperle, son of Artecoll’s inventor, German dermatologist Dr. Gottfried Lemperle. He says when the bovine collagen reabsorbs, the tiny spheres trigger the body to produce its own collagen to envelop them — making Artecoll a permanent plumper. Dr. no Busso, a dermatologist in Miramar, Fla., helped conduct the U.S. trial on the product, injecting 45 patients with either collagen or Artecoll.

Clinical trial participant with Artecoll injected in smile lines.

He followed his patients for a year and found that all of his Artecoll patients retained a plumped appearance, but that those who received collagen lost the fullness within six months. Lemperle, who is also CEO of Artes Medical in San Diego, the company formed to bring Artecoll to the United States, says the clinical trial of 250 patients found Artecoll was safe and lasted significantly longer than collagen. He is submitting the results to the government in July and expects the product to hit the U.S. market in 2002. Some European patients who received Artecoll 10 years ago continue to benefit, he adds. Besides the attendant risks of any bovine collagen product, Artecoll has been reported to cause inflammation in 1 in 10,000 cases in Europe. The complication wasn’t seen in the one-year U.S. trial, according to Lemperle. Busso says his main concern about Artecoll is that because the material is permanent, there is no room for doctor error. If too much is injected or if it’s placed too shallow in the skin, for example, a patient can be stuck with overcorrected lips or visible bumps in the skin. Dr. Sydney , a New York plastic surgeon who travels to Europe extensively teaching a method of fat injection he invented, says he has heard of reports there of Artecoll recipients developing granulomas — inflamed pockets of scar tissue — around the beads. ROOSTERS AND GERMS Considered by many to be the most promising among the next generation of fillers, Restylane and Hylaform — both cross-linked hylan gels created from hyaluronic acid — are already popular in Europe and Canada. Hyaluronic acid is syrupy natural polysaccharide that makes up a large part of the space around the cells in human skin and cartilage and helps give them elasticity. The gels have quickly gained a following in Europe, where people are skittish about bovine collagen because of the mad cow disease scare, even though injectable collagen comes from U.S. cows.

A form of hyaluronic acid called Synvisc has been approved by the FDA to lubricate creaky joints and can legally be put to other uses. There are some reports of doctors on the East Coast using it as a wrinkle filler, Kinney says. Brandt is conducting the U.S. clinical trial on Swedish company Q-Med’s genetically engineered gel Restylane. He says it looks good so far but it’s too early to come to a conclusion about its effectiveness and safety; he has injected 20 patients, with the first ones to receive it only two months ago. “It’s definitely more painful because it has no anesthetic, but it looks a little softer in the lip,” he says.

Injections of Restylane into the lips before and immediately after treatment.

Dr. Terrance Scamp, a plastic surgeon from Australia’s Gold Coast, presented results of a study on Restylane at the ASAPS meeting. He injected the lips and facial wrinkles of 224 patients and found it lasted an average of six months. Reports in Europe find about 1 in 10,000 people have an allergic reaction to Restylane. Neither of the hylan gels require skin tests. The product’s good safety profile in countries with high standards like Canada and Australia suggest it will be approved by the FDA within a couple years, said doctors at the ASAPS meeting. Plus, notes that since a form of hyaluronic acid already exists on the U.S. market for joint care, there shouldn’t be a problem getting these fillers on the market. Hylaform — made from hyaluronic acid extracted from rooster combs, a very concentrated source of the substance — will begin clinical trials in the United States soon, according to Dan Quinn, a spokesperson for Genzyme Biosurgery, which recently purchased rights to the product. Brandt says he has used it on several patients, including Barbara, to see if he wanted to be involved in clinical trials of the substance.

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Barbara says she thought Hylaform made her lips look softer and more natural than collagen or Dermalogen but found the injections quite painful. She also says she thought the volume lasted a bit longer than with the other products. Brandt likes the way it looks but says, “There’s not enough difference in duration. I’m pinning my hopes on Restylane to last longer.” Kinney says hyaluronic acid, while promising, may not be the slam dunk cosmetic surgeons are hoping for because it doesn’t appear to last a full year. A WORD OF CAUTION Dr. Elkwood, a plastic surgeon in Shrewsbury, N.J., urges caution with the newest fillers. “It’s very tempting to jump on the newest, sexist technology, but this needs to be balanced by years of experience,” he says. But America’s aging population doesn’t want to wait. “There’s a baby boomer that turns 50 every seven seconds in this country,” says Seattle plastic surgeon Dr. Phil Haeck. “These are the people who brought you health and fitness craze and they aren’t going to take their wrinkles sitting down.”