What’s New in Filler Substances?

Several materials have been used for the purposes of soft tissue augmentation over the past few decades. But not all are without problems. Read on to find out the pros and cons of a popular filler substance and a new filler that may soon be available for use in the United States. Collagen, although presently the most popular modality in the United States, has several drawbacks including its rapid degradation and an infrequent, but significant, potential for delayed hypersensitivity reactions, which obligates the physician to allergy test 4 to 6 weeks prior to injection. Because collagen is somewhat species specific, a variety of sources, including cadaveric and cultured autologous collagen, are being used in order to overcome this dilemma. Cost, time and the potential for disease transmission pose strong limitations with these materials.1 But a promising alternative may be on the horizon. Another type of cosmetic filler is showing promise. Hyaluronic acid products, particularly Restylane, have come into the limelight in the last several years. Currently the number-one cosmetic tissue filler in the world, Restylane has been shown to possess many properties that prove its value in several medical applications — particularly in soft tissue augmentation.2 Closer look at Restylane Hyaluronic acid, the main component of Restylane, is a polysaccharide, a ubiquitous component of all mammalian connective tissue. Residing in the extracellular space, it functions as a space-filling, structure-stabilizing, cell-protective molecule with uniquely malleable physical properties and superb biocompatibility.3 Hyaluronic acid matrices are extremely viscoelastic while preserving a high level of hydration. A strong correlation appears to exist between the water content in the skin and levels of hyaluronic acid in dermal tissue. As human skin ages, known alterations in hyaluronic acid content and metabolism occur, causing significant deterioration in the mechanical properties of the skin. These findings suggest a relationship between youthful skin and the presence of a strong hyaluronic acid network in the intercellular matrix.4 Although not available in the United States, Restylane, made by Q-med of Sweden, is already approved for cosmetic use in Canada, Australia and Europe. Using NASHA (non-animal stabilized hyaluronic acid) technology, Restylane is produced by cultured Streptococcus. Although its elastoviscous properties are ideal in its naturally produced state of unbranched polysacharride chains, hyaluronic acid has a short half-life of 1 to 2 days in all connective tissues. Therefore, in its original form, hyaluronic acid degrades too quickly to be used for soft tissue augmentation. However, by introducing cross-links between the polysaccharide chains, a water-insoluble viscoelastic gel is created, which retains the biocompatibility and biological properties of the natural substance and provides prolonged residence time in dermal tissue. The greater the amount of crosslinking, the greater the viscosity and insolubility of the gel. The Different Forms of Restylane Three different Restylane products are currently distributed by Q-med — Restylane, Restylane Fine Lines and Perlane. In all three agents, the concentration of hyaluronic acid is constant at 20 mg/ml. What differs between them is the size of the hyaluronic particles expressed in the number of gel particles per milliliter. - Fine Lines, which has the smallest particles, is the least viscous of the three. This product is meant for placement in the superficial dermis to treat fine lines and superficial defects. You’ll also use a 31-gauge needle to inject it. - Restylane, which has larger particles and is injected through a 30-gauge needle, is best suited for defects in the mid-dermis, such as moderate nasolabial fold rhytides and lip augmentation. - Perlane, the most viscous of the products, has the largest particles and is placed in the deep dermis and superficial subcutaneous tissue. This product is best suited to treating deep folds and facial contouring. Injected through a 27-gauge needle, Perlane can often be layered with either Restylane or Restylane Fine Lines. Because of the varied sizes of the needles and the lack of anesthetic in the gel, you should use some level of anesthesia applied either topically or with nerve blocks. Restylane Versus Collagen Restylane has several properties that prove its superiority to many of the cosmetic fillers currently used, particularly collagen. Identical in all living tissues, hyaluronic acid is extremely biocompatible, posing significantly less risk for allergic hypersensitivity reactions that are commonly associated with bovine collagen. Currently, about 3% of the population shows a delayed hypersensitivity reaction to collagen testing.5 Although the exact statistics for allergic reactions to Restylane are controversial, they’re significantly less, ranging from .0005% to 0.42% of treated patients.9 Also, allergy testing is not required prior to using Restylane for soft tissue augmentation. This offers a significant convenience for patients who would otherwise have to wait about 6 weeks before treatment. In addition to its biocompatibility, Restylane is derived from a bacterial, not an animal, source. So there’s significantly less risk of disease transmission compared with bovine or cadaveric collagen. Lastly, according to anecdotal evidence, Restylane may last longer in tissue than current collagen products because of the cross-linking of the polysaccharide chains. Although this claim hasn’t yet been proven in comparative studies, FDA trials are currently underway to evaluate it. In 1998, Duranti et al conducted one of the original clinical studies. They followed 158 patients and found that 78% of patients maintained a moderate to marked clinical improvement of treated sites after 8 months. Although 12.5% of patients experienced immediate localized and transient adverse events, no long-term or delayed-type reactions were noted.6 Since then, several papers have cited more long-term adverse reactions thought to be caused by a delayed hypersensitivity reaction.7,8,9 Q-med has postulated that possible impurities in the fermentation process have caused these reactions. The company has altered the production and purification processes to minimize this risk. Future of Hyaluronic Acids The other hyaluronic acid filler currently under investigation is Hylaform. Made from rooster combs rather than bacteria, Hylaform appears to have different chemical properties that have yet to be investigated in clinically comparatives studies.10 Nonetheless, Restylane and other hyaluronic acid products show remarkable promise for the future of soft tissue augmentation. With the potential for providing a safer, more convenient and longer lasting result, we eagerly await their release in the U.S. market. Dr. Brown is director of cutaneous surgery at the Skin Institute of New York In New York, NY, and is assistant clinical professor of dermatology at NYU School of Medicine, New York, NY. Dr. Frank is in private practice as the director of the Fifth Avenue Dermatology and Laser Surgery Center in New York, NY. He’s also clinical instructor of dermatology at NYU School of Medicine.