Come'on Doc, there's room for one or two more drops!!
Since the introduction of injectable collagen for improving or eliminating facial wrinkles, many new agents have been introduced with safer and more effective properties. Techniques of injection have evolved to less invasive ones, and their combination with other minimally invasive therapies for the skin, such as microdermabrasion, chemical peels, and radiofrequency-based and light-based treatments, has increased the degree of esthetic results and the level of satisfaction for patients and physicians. There have been many discussions theorizing the attributes of the perfect filling agent. We want a product that can be administered safely, conveniently, rapidly, and painlessly and without leaving any traces that it has been applied. We want a product that does not result in any complications and that lasts a long time. The ideal substance should be “biocompatible, nonimmunogenic, nonresorbable, nonpyogenic, noncarcinogenic, inexpensive, and nonmigratory, with the ability to be stored, shaped, removed, and sterilized easily”. We have not yet achieved this level of perfection, but the nonanimal-derived, stabilized hyaluronic acid products are the current state of the art, fulfilling much of our desired criteria.
HISTORICAL PERSPECTIVE
The history of modern soft-tissue augmentation dates to the late 1800s, when injectable fat was first used for tissue augmentation. Since then, many substances and devices have been marketed for the purpose of cosmetically improving soft-tissue defects and wrinkles. Liquid injectable silicone has been used since the 1940’s as a soft tissue filler. In the 1940s, Dow Corning (Midland, MI) produced DC-4, its first silicone containing product used as a lubricant in military bombers. The 1940’s also witnessed the first use of silicone in humans for cosmetic improvement. By the 1960’s misuse was rampant, with large volumes of pure and adulterated forms of silicone being injected with subsequent complications. In 1974, Dow trademarked a refined liquid silicone with established safety and efficacy. Nevertheless, the controversy that swirled around silicone breast implants led to the demonization of injectable silicone as well. The American Society of Dermatologic Surgery responded in 1993 by concluding that the use of liquid injectable silicone by the microdroplet technique is an efficient and safe procedure for many individuals1. Two U.S. Food and Drug Administration (FDA)-approved medical grade liquid injectable silicones are available today. Adatosil (Escalon Medical Corp., Chicago, Illinois) and Silikon (Alcon Laboratories, Fort Worth, Texas) are approved for the tamponade of retinal detachments and their off-label use for soft tissue augmentation is permitted by the FDA’s Modernization act.
For the last 2 decades, the most widely available and widely used substance for filling in facial wrinkles has been collagen. Approximately 25% of the protein in the human body and 75% in the skin is collagen. Investigators in the early 1970’s developed a purified human and bovine [cow] collagen that underwent successful clinical trials in human patients. Subsequent to these results, Zyderm I was developed by the Collagen Corp. and tested by 14 investigators from 1977 to 1978. In 1981, after 6.5 years of development and clinical trials, Zyderm I received FDA approval for soft tissue augmentation. Injectable bovine collagen has been used for facial rejuvenation since the 1980’s. It requires skin testing before it can be used as a filler. The second generation, derived from human fibroblast cell culture does not require prior skin testing. The average longevity of correction with these products is about 3 months. Collagen fillers produced from bovine sources have a risk of inducing allergic reactions. Sensitivity skin tests prior to treatment are recommended for bovine derived collagen but not for human-derived fibroblast collagen products.
In the last decade, hyaluronic acid (hyaluronan) has been shown to possess many properties that suggest its value in soft-tissue augmentation. Hyaluronic acid is a polysaccharide found in the extracellular matrix of all tissues of all vertebrates and comprises 56% of the extracellular matrix of human skin. It is composed of a water-loving sugar similar to clear gelatin. Hyaluronic Acid Products produce longer lasting results and fewer hypersensitivity reactions than collagen products:
Restylane (Medicis, Scottsdale, Arizona), FDA approved December 12, 2002, has 20 mg/mL of hyaluronic acid with a gel bead size of 250 µm and 100,000 units per mL.
Perlane (Q-Med, Uppsala, Sweden), approved in the United States, has 20 mg/mL of hyaluronic acid with a gel bead size of 1000 µm and 10,000 units per mL.
Restylane Fine Lines (Q-Med, Uppsala, Sweden), not approved in the United States, has 20 mg/mL of hyaluronic acid with a gel bead size of 100 µm and 250,000 units per mL.
Restylane, Perlane, and Restylane Fine Lines are NASHA products, biosynthesized from a nonanimal source. Restylane is used for the filling of fine lines and moderate wrinkles and lasts an average of 9 months.
Perlane is used for the filling of deeper furrows and contour irregularities. Because it is thicker, it can allow for more effective filling and lasts longer than Restylane. Restylane can be layered over Perlane for correction of residual superficial irregularities. Restylane Fine Lines (not available in the United States) is used for the correction of delicate upper lip wrinkles.
Sculptra (Polylactic Acid)
Sculptra (Dermik Laboratories, Berwyn, Pennsylvania) is synthetic polylactic acid powder (0.15 g per bottle) that has to be mixed and put into suspension in four to five mL of diluents (half sterile water and half lidocaine) immediately prior to injection to avoid clogging of the 26 gauge needle (supplied with product). This product works well to fill in broad irregular areas. It must be injected subdermally. Because the amount of correction improves with time, a gradual filling in the contour defect is recommended. Rather than aiming for complete correction in one session, partial correction is augmented in 3- to 4- month intervals3.
Artefill [Polymethylmethacrylate (PMMA)]
Artefill (Artes Medical, San Diego, California) is composed of uniform polymethylmethacrylate (PMMA) beads (30-42 µm in diameter) suspended in collagen. The collagen acts as a temporary filler, and the microspheres create an inflammatory response with secondary collagen production and a longer lasting effect. Because it contains bovine collagen, it requires skin testing before use3.
Matridex (Hypromellose, dextanomer DEAE)
Matridex (BioPolymer GmbH, Germany) is hypromellose, dextranomer DEAE suspended in hyaluronic acid and cross-linked hyaluronic acid. The hyaluronic acid provides temporary filling without the need for pretreatment skin testing and the hypromellose and dextanomer DEAE (positively charged microparticles) promote fibroblast formation and collagen neogenesis, inducing a longer lasting effect. It is not approved in the United States.
Alloderm (Acellular Cadaveric Dermis)
Alloderm (Lifecell Corporation, Branchburg, New Jersey) is a solid acellular biological implant that is useful in eyelid and lip reconstruction and for repairing large facial contour deformities. Human dermal tissue is harvested from cadavers. The cells, which are targets for the immune response, are removed without altering the collagen and extracellular matrix of the dermis. This immunologically inert tissue then serves as a framework to support revascularization and cellular repopulation. Cymetra (Lifecell Corporation) is its micronized, injectable form. It is supplied as a cryofractured, dried, acellular, particulate dermal matrix. When refrigerated, it has a shelf life of 2 years. We have found that when it is injected for lip augmentation considerable swelling and rapid resorption are the rule.
