Guide to Filling Wrinkles

Facial wrinkles are a new phenomenon. Until a few centuries ago, humans didn’t live long enough to become wrinkled. In fact, the presence of wrinkles foretells aging. A healthy, youthful appearance wanes with advancing years. Every glance into the mirror reminds us of our mortality.Attempts to correct wrinkles by inflation with fillers began as early as 1902. Paraffin (wax), silk, celluloid, latex, and Vaseline were injected into the face. These procedures were abandoned twenty years later because of disastrous complications. One surgeon actually combined various ingredients in a vegetable grinder and injected them into the face.

Surgeons have long searched for the ideal filling material—one that was simple to use, inexpensive, lasted a long time, and had no complications. Until Restylane was introduced in Europe in 1996 only one wrinkle filler was in common use. For two decades collagen was the only choice. And until 2003, it was the sole filler in the United States. Now many fillers are in use around the world and more are on the way. Only time will tell which are useful and which are dangerous. As Peter McKinney, M.D., C.M., professor of plastic surgery at both Northwestern and Rush medical schools, says, ‘‘The one that lasts longer with fewer problems wins.’’In 2005, there were 40,000 Radiesse injections, 221,000 collagen injections, 1,194,000 hyaluronic acid injections, and 35,000 Sculptra injections in the United States alone.Some fillers are designed to be placed in the skin and some belong underneath the skin, in the fat. Fine-wrinkle filling requires different materials than deep folds. After deciding on the depth of the material, we consider how long the material lasts and its cost.While no surgeon wants to be the last to perform a new procedure, it is not wise to be the first, either. New fillers need to last for a long enough time to be cost-effective but not cause short- or long-term problems. Consumers should be sure that their physician purchases fillers from approved sources within his own country. If a product is brought in from outside the country, there is no way to be sure the product is genuine.Fillers are not just used for filling wrinkles or folds. Innovative plastic surgeons are now using fillers to reshape noses, chins, jawlines, and virtually every area of the face. CollagenCollagen is a protein made from cow skin. It is processed, mixed with the anesthetic lidocaine, and made into a paste that is injected into fine wrinkles. Collagen was first used in the late 1970s but did not become popular until it was commercially available in 1981. As a foreign protein, collagen is attacked and digested by the human body.The body can become confused, making antibodies against the cow collagen and even the body’s own collagen. The result may be an autoimmune disease, such as dermatomyositis, rheumatoid arthritis, lupus, or scleroderma, in which one’s own collagen is attacked.Collagen lasts between two weeks and six months, after which the injection must be repeated to maintain the effect. Under the microscope, we can see that the body digests the collagen within six months. Allergic reactions may result; therefore, the patient’s skin must be tested prior to the injection. One, or even two, tests are usually performed a month beforehand. Collagen is marketed by the Allergan Corporation under the names Zyderm and Zyplast. The average cost in the United States for an injection is about $400.Cosmoderm and CosmoplastCosmoderm is human collagen. It was introduced in 2003, in an attempt to decrease the allergic reactions to cow collagen. Made from human skin tissue that is grown in a laboratory, Cosmoderm, strengthened by the chemical glutaraldehyde, is not as thick as Cosmoplast. My major objection to Cosmoderm is that it is made from dead humans. There is no way to sugarcoat that fact. And there is no way to assure with total certainty that a disease will not be passed along from the dead donor to the recipient of the collagen. Still, infectious diseases such as AIDS or hepatitis, West Nile virus, or Cruetzfeld-Jacob disease (the human mad-cow disease) have never resulted from a Cosmoderm injection.On the other hand, every type of tissue ever transplanted from one human to another has eventually been linked to infectious disease transmission. Hepatitis C has been passed along, even when the organ donor tested negative! Diseases that we can’t even test for yet might be in the tissue. There has been one death and at least two dozen serious infections from the transplantation of other types of contaminated tissue from one person to another.In 2003 the U.S. Centers for Disease Control and Prevention reported that a tissue donor had transmitted the hepatitis C virus to eight people. And there is no way to test for Cruetzfeld-Jacob disease. I worry about human cadaver materials causing disease in patients who simply want to look better. Diseases can be transmitted even after the most stringent testing. In 2005 bone, skin, and tendons were illegally taken by a New Jersey tissue bank from New York funeral homes and sold to companies for implantation into other humans. Lifecell Corporation, producer of the collagen implants Alloderm and Cymetra, was one of these companies. These tissues were never tested for infectious diseases. Scary enough that I never use a human product unless the problem is life threatening. Cosmoderm and Cosmoplast cost about $100 more than cow collagen.EvolenceThis is a brand-new injectible made from pig collagen. The manufacturers have tinkered with the molecule and linked it to a sugar. This appears to make it a ‘‘super-collagen’’ capable of lasting far longer than standard collagen. Because it is made from collagen, allergies can occur and so skin tests are necessary. The company says it can last over fifteen months. It is available in Europe, Canada, Japan, and Israel, but not yet in the United States.CymetraThis material contains collagen, elastin, and other proteins from human cadavers. It is the injectable form of Alloderm. While infectious diseases have never been transmitted with Cymetra, the very possibility makes many plastic surgeons and patients nervous. Transplanted Cymetra lasts about two months. It should not be used around the eyes. It is not a particularly popular filler.FascianThis is basically human collagen that is taken from fascia (connective tissue) of the calf muscle. The material is used to fill wrinkles, scars, nasolabial folds, and depressions. Fascian may be replaced with your own collagen at some point, so there is some chance of permanence. At $85 per syringe, Fascian is much cheaper than other fillers. But I do not believe that we should choose a filler material solely on the basis of price. As with other cadaver-derived products, I get nervous since this product is taken from a human.IsolagenIn this interesting approach to wrinkle filling, the Isolagen Corporation grows pure cells in the laboratory. A small piece of skin is taken from a patient and sent to the Isolagen lab where, in six weeks, millions of cells are produced. The cells, called fibroblasts, make collagen. They are sent back to the doctor and injected into the patient. Presumably they will then ‘‘live long and prosper,’’ growing new collagen within the patient’s skin. This procedure is currently under study in the United States. Restylane, Perlane, Hyalaform, Juvederm, and CaptiqueThe early 2000s saw the race for a better wrinkle filler. Half a dozen companies waged a furious battle to gain early market share for what they hoped would be the next blockbuster cosmetic drug—the next Botox.Restylane was approved in Europe in 1996 and in the United States in 2003. It is made of hyaluronic acid, created by bacteria through the wonders of genetic engineering. Because no animals are used to create this product, there is no chance of contracting infectious disease. And because this sugar-like substance is already normally present in our bodies, skin testing for allergy is not required. Although the FDA says that Restylane is comparable to Zyplast collagen at six months, many physicians find it to be superior. Under the microscope, this material is seen to last nine months. Bruising, swelling, and pain on injection are common and depend on the skills of the doctor.Restylane fills wrinkles nicely and clinically lasts between six and twelve months, although this duration is not guaranteed. Some patients need a second touch-up injection a few weeks after the first because swelling occurs immediately, making precise injections impossible.Restylane is not destroyed by the body. It simply diffuses into the skin, like a drop of ink diffusing into a glass of water. Gradually it settles into the skin, and the wrinkles are exposed again.The company that produces Restylane also produces lower- and higher- viscosity (thickness) products. Perlane is Restylane’s thicker cousin. It will be used to correct deep folds and to plump lips. Restylane Fine Line is a thinner material that will be used in fine wrinkles, and Restylane SubQ uses larger particle sizes to fill deeper folds and to build up the cheekbones and the chin. These products will serve to confuse physicians and consumers since their indications overlap.Juvederm, approved in 2006, is Allergan’s answer to hyaluronic acid. Juvederm comes in three different viscosities. Like the Restylane products, the thicker materials are used for deeper folds; the thinner fillers are used for more superficial wrinkles. Juvederm claims to have the highest concentration of cross-linked hyaluronic acid, allowing the chemical to stay in the body longer than competing products. Because Allergan also makes Botox, the co-marketing of these two substances will propel Juvederm’s popularity.Restylane is today’s ‘‘injectable of choice.’’ It has caught on rapidly. Not only is it used for fine wrinkles, but creative uses keep being described. It fills folds, scars, and various depressions. It is being used to plump up the eyebrows, giving a lifting effect. Used in the lower eyelid, it pushes up the lid, shaping it and filling in the ‘‘tear trough.’’ It can highlight the bones in the upper eyelid and increase the size of lips. It has even been injected into sun-damaged cleavages! Because Restylane is a gel, it cannot be mixed with local anesthetics. Without lidocaine, the injections hurt and so some sort of anesthetic is usually used. Outside the United States, different types of Restylane are available. One, an experimental hyaluronic acid mixed with the anesthetic lidocaine, is currently in development. Early reports indicate that injection of this material hurts less than other hyaluronic acids. Restylane is most commonly injected into the fine wrinkles around the mouth and face. It is less effective for the deeper wrinkles and folds. It can also fill depressions of the face and nose.Other brands of hyaluronic acid are also available. Hyalaform is made from roosters’ combs, as opposed to the test-tube production of Restylane. Plastic surgeons say that Hyalaform may disappear sooner than Restylane—perhaps after just three months. Restylane packs four times as much hyaluronic acid into its product as its competitors, which may explain its better clinical results. There may be a higher allergic reaction rate with Hyalaform than Restylane.PuragenThis is a souped-up hyaluronic acid. The Mentor Corporation has altered the molecule to make it more stable. That means it takes longer to fade away. Puragen Plus also has the anesthetic lidocaine added to the gel, making injections less painful. Puragen is already approved in Europe and will most likely be approved in the United States.RadiesseWhen a product changes its name, it reminds me of a Dragnet episode: ‘‘The names have been changed to protect the innocent.’’ This injectable product, formerly called Radiance, is now called Radiesse (apparently, the original name was too close to other medical products). Radiesse is made of calcium hydroxylapatite, the building block of bone and teeth. Other chemicals in the mix have long been allowed as the carriers for injectable medications. Radiesse is completely synthetic; no animal products are used in its production. That gives assurance that infectious diseases cannot be contracted through its use. The nontoxic chemical degrades over time, broken down into calcium and phosphate, normally present in the body. Collagen (or scar) surrounds the degraded Radiesse particles, allowing the filler to last a long time.Radiesse is not used for fine wrinkles but for deeper depressions, such as the nasolabial folds. Approved by the FDA for tissue filling in 2006, its list of uses has been steadily growing. Not only has it been used to fill the marionette lines between the corner of the mouth and chin, but it has also corrected sunken cheeks, filled dimples, and rejuvenated the depression between the jowl and the chin. Radiesse is also being used as a nonsurgical implant to make the chin and cheek bones larger. Radiesse is increasingly popular for correcting minor deformities of the nose after fractures or rhinoplasty. Almost magically, when Radiesse contacts bone, new bone is formed. When not touching bone, it creates bulk and scar. Part of the improvement may be permanent, although the manufacturer states that this filler lasts between one and two years. Some surgeons claim it lasts longer.The placement of Radiesse is truly an art, and results will vary with the skills of the surgeon. Its injection is really surgery: surgeons use the injecting needle to break attachments of skin to underlying tissue before the injection, and they use the material like steel rebar in concrete—crossing folds to reinforce them and hopefully stall recurrence.No allergic reactions have been reported to date, and no skin test is needed. Radiesse cannot be used to make lips larger, however. In a third of patients it clumps and forms lumps in the lips. If these lumps occur, the lip must be punctured and the material squeezed out. This usually solves the problem.Radiesse costs the surgeon $295 for a 1.3 cc syringe. The average cost for a Radiesse injection is $900.SculptraSculptra was approved as a filler in 2004. It has been marketed outside the United States, as NewFill, since 1999. Chemically similar to suture material, Sculptra (poly-L-lactic acid) currently is approved only for filling facial fat loss (lipoatrophy) in HIV-positive patients. Injected into the deep dermis, it may last as long as two years, although one study showed it had disappeared in four months. It may last longer, because it stimulates the body to make a collagen scar around the material. As with Radiesse, lumps may appear when it is injected into the lips. But there have been troubling cases of stubborn lumps in other parts of the face, prompting a warning about the long-term effects. I expect that this material will soon be approved for cosmetic purposes. It will then be used to fill nasolabial folds, marionette lines, and other facial hollows.Unlike Restylane, Sculptra can be mixed with lidocaine to lessen the pain of the injections. New, creative uses for Sculptra and other fillers are described almost daily. Sculptra has even been used, off-label, by podiatrists to plump up unattractive feet! The average cost for a Sculptra injection is $1,000.AutologenThis novel product is collagen made from a patient’s own skin. A piece of skin is processed in a laboratory and returned to the patient’s doctor for injection as collagen. Despite the hope that the collagen would be permanent, since it is the patient’s own tissue, it only lasts as long as cow collagen. PlasmagelThis substance, not particularly popular, is made from the patient’s own blood and vitamin C. It lasts about three months. I do not know any plastic surgeons who use it.SiliconeSilicone was used extensively in the 1970s. I remember ‘‘Imus in the Morning’’ stating that the greatest achievement of a Playboy model was enduring the pain of silicone injections into her breasts. In fact, silicone liquid has been injected into breasts and faces for more than thirty years. It sounds like a good idea, in that it does not break down over time. However, most authentic plastic surgeons have seen disasters from these injections. The FDA says silicone can cause swelling, reddening of the skin, lumpiness, and soft-tissue tumors. The scar around the silicone can be very thick, creating nodules, or it can be thin, allowing the material to drift through the tissues, ending up via gravity in the most southern location.Once injected, the game is over. If the area becomes infected, the infected tissue needs to be cut out. Countless women have undergone mastectomies or removal of whole sections of the face because of infected silicone. The American Society of Plastic Surgeons says injectable silicone can harden, migrate, cause inflammation, and kill skin. As a result, the FDA banned it in 1991. The next year, it enforced its ban by having three noted New York dermatologists sign an agreement to stop injecting liquid silicone. At the time, FDA commissioner David Kessler, M.D., said, ‘‘People who undergo these injections are exposing themselves to unknown, potentially dangerous risks.’’ Again in 1993, the FDA took action against a Miami plastic surgeon who had injected liquid silicone.The next year, silicone oil was approved by the FDA for treating retinal detachment in AIDS patients. This created an avenue for physicians to once again inject silicone into wrinkles, arguing that its use would be off-label and not illegal. In 2004, highly purified silicone oil was injected into the atrophied faces of AIDS patients, restoring contour without side effects. Long-term problems were not assessed, however. In 2006, an unlicensed nurse injected silicone into a patient’s buttocks. Some of the silicone traveled through the bloodstream into the lungs, causing respiratory failure.I know that there are still physicians who inject silicone. I wonder why. As a patient, I would select a physician who practices ‘‘safe surgery’’ and not ‘‘what I can get away with’’ surgery. Artecoll and ArteFillArteFill consists of tiny balls of plastic (polymethyl-methacrylate) mixed with the anesthetic lidocaine in a collagen base. (Hard contact lenses are made out of this material.) Once injected, ArteFill becomes surrounded by scar. A plastic, it never breaks down. Like liquid silicone, it violates that basic principle of plastic surgery: any foreign substance that doesn’t dissolve must be removable. ArteFill can’t ever be removed. A 2004 study extolled the virtues of Artecoll, another filler, showing clinical improvement in facial wrinkles for up to a year. But plastic surgeons who fail to study the history of silicone are doomed to repeat its problems.Artecoll and ArteFill sound good, since they permanently fill in scars and wrinkles and plump lips. However, like silicone, they cause lumps and areas of inflammatory scarring called granulomas. These problems prompted the Swiss Society for Dermatology, the Swiss Society for Plastic Reconstructive and Aesthetic Surgery, and the Swiss Society for Aesthetic Medicine to advise against the use of Artecoll and silicone in the face. In addition, it can migrate to unwanted areas. Artecoll has been used on four hundred thousand patients in Europe and around the world since 1994 and was just approved in the United States. A skin test is required before injection because the filler contains highly allergenic collagen.Gore-TexWhile not technically injectable, tiny pieces of Gore-Tex (expanded polytetra- fluoroethylene, e-PTFE) are threaded into fine wrinkles. Poor results are frequent. Scar is made around the Gore-Tex and is often visible through the skin. A foreign material, it can become infected and extrude through the skin. I have removed Gore-Tex from many patients. A fine material for dental floss and shoes, it is a poor wrinkle filler. The material is supposed to be inert and not biodegradable, but in 2006 the Environmental Protection Agency found that Teflon (the closely related chemical polytetrafluoroethylene) is ‘‘a likely carcinogen.’’ In November 2006, the company voluntarily withdrew all Gore-Tex products from the plastic surgery market.Surgisis Soft-Tissue GraftAn interesting material, not technically an ‘‘injectable,’’ Surgisis is a sheet of collagen taken from pig intestines. All the cells are removed and the material is sterilized. Tissue grows into it when implanted into humans. The material is many times stronger than human tissue and therefore can strengthen the abdominal wall in tummy tucks. In the nose, it can smooth bumps. Surgeons are using it to help pull up tissues in face-lifts and to make lips larger. Time will tell how satisfactory this material is in the long run.