DERMAL FILLERSWith so many choices, selecting the appropriate filler, or fillers, for our patients can pose challenges. Of the three dermal fillers evaluated in this article, two only very recently received clearance from the FDA — ArteFill, which was granted clearance at the end of October last year, and Radiesse, which was granted clearance by the FDA late last December. The third, Sculptra, received FDA clearance nearly 3 years ago. Here, we will explore these dermal filling agents, discussing the basics of each, the advantages and disadvantages of each, as well as advice for how to achieve optimum outcomes with each. Sculptra/NewFill By Leslie Baumann, M.D. Injectable poly-L-lactic acid (PLLA) is a synthetic, biodegradable, biocompatible, immunologically inert polymer that is derived from the alpha-hydroxy-acid family.1-3 Now marketed under the trade name Sculptra (Dermik Laboratories, Sanofi-Aventis). Sculptra is not yet FDA approved for use in facial wrinkles but has been used off-label for this indication for several years in the United States. However, a cosmetic indication is expected later this year. Sculptra is composed of PLLA microspheres, sodium carboxymethylcellulose and non-pyrogenic mannitol.Poly-L-lactic acid has been assessed in several toxicology and biocompatibility studies, as well as in clinical studies.2,4-7 Subsequently, PLLA has been shown to be well-tolerated and effective in various clinical applications. Currently, injectable PLLA is approved in Europe and Canada for HIV-associated facial lipoatrophy. It has been used widely in Europe since 1999.8 It is also approved in Europe and Canada, and is quite popular, for cosmetic enhancement, particularly for increasing depressed facial areas (e.g., wrinkles, folds, and scars) and atrophic areas (e.g., the eyes, cheeks, temples and perioral areas). In the US, PLLA is approved only for the treatment of HIV-associated facial lipoatrophy. This novel 3-D cosmetic agent is believed to promote neocollagenesis via stimulating fibroblasts, resulting in a gradual restoration of facial volume.9 The sundry applications of polylactides include uses as resorbable suture materials in ophthalmologic, neurologic and thoraco-abdominal surgery, and increasingly widespread use as support materials in maxillofacial surgery, periodontology and stomatology.10 The safety, tolerability, and efficacy of PLLA has been demonstrated for treating deep facial lines and imparting longer-term volume replacement in nasolabial areas in several studies,11,12 with optimal cosmetic benefit typically observed at 2d to 4 weeks post-treatment and results lasting for several months.13-15 Skin thickness increases have been shown to last for up to 2 years.16Previously, injectable PLLA was marketed as NewFill. Unfortunately, it was frequently incorrectly injected and in excessive concentrations, yielding some poor results, adverse reactions, and inconsistent physician interest in the product. Recent clinical experience with PLLA, employing different dilution and injection techniques, has shown it to be a safe and effective method of treatment for facial wrinkles.17 However, the technique used to inject Sculptra is very different than that used with other fillers. In fact, Sculptra is not considered to be a true dermal filler because it “stimulates the dermis” to make collagen rather than “filling the dermis” with a substance such as collagen. Results of Sculptra injections are not immediate and a series of injections is required to reach the best aesthetic result.The microparticles of PLLA degrade slowly. It is thought that this phenomenon coupled with the size of the microparticles renders Sculptra able to stimulate collagen production, thus improving volume in lipoatrophy patients while resulting in a correction that lasts longer, on average, than most filling agents.18,19The mechanism of action and proper technique of administration of Sculptra require practitioners to concentrate on restoring volume to a selected area of the face rather than a particular wrinkle.11 The technique of replacing volume rather than filling a wrinkle is very different than that used for dermal fillers. Use of Sculptra injections is more similar to fat injection procedures than those employing collagen or HA fillers. The number of treatments required for optimum correction depends on the volume of the deficiency.16 In my experience, pre-menopausal women require three to four treatments at monthly intervals while post-menopausal women require five or more. Other predictors of how many treatments are necessary are not known at this time, and there is variability among patients. AdvantagesSculptra treatment provides a minimally invasive, effective, and prolonged (18 to 24 months) facial enhancement correction of wrinkles, depressions, and laxity with a low frequency of side effects.11,18,20 It enhances facial volume and dermal thickness imparting a more youthful look to the skin. Sculptra is my product of choice for use in the “tissue paper” appearing skin around the frontal lower cheeks and to improve malar flattening and to enhance the cheekbones. Facial volume loss in the middle and lower face, jawline laxity, and nasolabial folds have all been treated successfully with Sculptra.11With a long and proven safety record, PLLA has been used successfully in various medical devices for more than 30 years.17 New product guidelines and injection techniques have been established and have led to a lower incidence of side effects.21 The new guidelines consist of a greater dilution and deeper injection technique.22 The longer-term duration of Sculptra can be considered an advantage. However, because the results are often not immediate, Sculptra is often combined with other long-lasting fillers such as Restylane to increase patient satisfaction. Lidocaine and epinephrine can be added to Sculptra to decrease pain and the incidence of bruising.DisadvantagesThe agent PLLA has been associated with significantly higher rates of post-injection site pain, localized bruising and localized swelling. One reason for this is that a larger bore needle (25 gauge) is used as compared to that for dermal fillers (30 gauge). Adding lidocaine to the diluent decreases the pain on injection significantly. The larger needle also leads to an increased incidence of bruising but this can be mitigated by adding epinephrine to the Sculptra and by applying arnica gel to the patient’s face after the procedure. In addition, bromelain supplements (500 mg twice a day) can be used to prevent and treat the bruising. Small papules can occur in areas with a lot of movement such as around the eyes and in smoker’s lines above the lips, so these and other hyperkinetic areas should be avoided. In earlier trials of PLLA used to treat HIV-related lipoatrophy, there were high rates (31% to 52%) of injection-site papules reported.6,23 In a report on three female patients, authors noted intradermal injection of NewFill resulted in giant cell granulomatous reactions and consequently cautioned that great care should be taken when intradermally injecting this product.24 However, adverse events related to the NewFill device, such as subcutaneous papules and areas of induration, have been primarily attributed to incorrect injection technique.17,21Refinements in injection technique (in particular, using a more dilute product, avoiding over-correction, superficial placement, and post-injection massage) have resulted in a lower reported incidence of papules and nodules after PLLA treatment.21,25-27 Although adverse side effects are less frequent now, the adverse events reported in association with PLLA remain nodule and hematoma formation, as well as pain at the injection site.28 Nodule formation is highly unlikely now if practitioners adhere to the new recommendations to dilute PLLA powder and inject it into the deeper subcutaneous tissue.25 However, small papules in areas of hyperkinetic movement are frequently seen, so these areas should be avoided. In addition, a small number of patients will develop tiny, palpable papules that are not apparent by visual observation but can be palpated. Although I have not had any patients upset by these, I always warn them ahead of time that there is a chance that these palpable papules, which are about 1 mm to 2 mm in diameter, will develop. The exact incidence of these papules is not known, but the nodules are rare and thought to occur in less than 3% of cases. (References for this article are available on www.skinandaging.com.)RadiesseBy Wm. Philip Werschler, M.D.Composed of calcium hydroxylapatite (CaHA) microspheres suspended in an aqueous gel, Radiesse fills and stimulates the body to produce new collagen for immediate results that last about 1 year or more. Manufactured and distributed by BioForm Medical, Inc., Radiesse has been approved by the FDA for the correction of moderate to severe facial wrinkles and folds and for facial fat loss in persons with human immunodeficiency virus.AdvantagesRadiesse builds natural tissue, and it’s referred to as a biostimulator. I call it the own vs. rent philososphy. It’s kind of like a lease-to-own vs. rent-to-own situation. With Scultptra, you have wait for the body to grow tissue based upon the process of neocollagenesis. The advantage of Radiesse is that you have immediate correction as well as long-term correction. The typically quoted range of duration is 9 to 18 months. This dermal filling agent also has an excellent safety profile. In the clinical trials, no granulomas were reported. The product is also efficient. In clinical trials, when comparing how much material was needed to attain a desired result, it was one-third more efficient than hyaluronic acid. No skin testing is required, and Radiesse can be stored at room temperature.DisadvantagesIt is injected with a 27-gauge needle, so this size needle is a little larger than what is typically used for filler agents, and this can lead to bruising and bleeding. An anesthetic is recommended. Also, the product remains somewhat malleable in the tissue for up to 2 weeks. Because of that, depending on how it’s placed in the tissue, patients can manipulate and affect the final outcome of the product. However, on the good side, the practitioner also has time to go back and adjust the correction for optimal aesthetic outcome. Due to the product’s malleability, it’s ideal to do multiple passes with the microthreading technique. However, these multiple passes can increase bleeding and bruising. Also, afterward, Radiesse can ache in the tissue for up to several days. Patients can complain of the feeling of a “headache” in their face. I’m not sure if this is a result of using the microthreading technique or whether it’s caused by the composition of the product. However, acetaminophen can adequately treat the pain associated with this symptom.Another point that can be an advantage or a disadvantage is the long lasting nature of Radiesse. It can be viewed as a disadvantage if the patient is disappointed with the effect, then he or she has to live with it longer ARTEFILLBy Rhoda S. Narins, M.D.ArteFill was approved in late October of last year. Its predecessors were ArteColl and ArteFast. ArteFill is an improvement on those products. It differs from previous substances. ArteFill is indicated for the correction of nasolabial folds, and it’s the first and only non-resorbable aesthetic injectable implant approved by the FDA. ArteFill contains a proprietary combination of microspheres of polymethylmethacrylate (PMMA) that are suspended in a carrier gel containing purified bovine collagen. The size of the microspheres range from 30 to 50 microns.The bovine collagen comes from a closed U.S. herd, and the PMMA beads are like Lucite. The smooth beads are uniform in size, and no beads are smaller than 20 microns, which is good because smaller beads tend to cause the granulomas.The way that ArteFill differs from ArteColl include the following: 1. Collagen made from a closed U.S. herd (more controlled material and prepared with lower allergenicity).2. It is made in the United States. Recently, Artes Medical completed a 5-year follow-up study of 145 patients who were treated with ArteFill in the U.S. clinical trial. In addition to demonstrating the safety profile of ArteFill, the study showed statistically significant (p<0.001) improvement in patient wrinkle correction 5 years after the patient’s last ArteFill treatment. Study participants also had a statistically significant (p=0.002) improvement in wrinkle correction at the 5-year point compared to the 6-month evaluation period. In addition, according to a report from Artes Medical, more than 90% of the physician assessments were either “completely or very successful.” Patient evaluations also indicated that more than 90% of patients were either “very satisfied” or “satisfied.”Because it includes collagen it must be refrigerated. But like collagen it has lidocaine in the product, so it’s not painful for patients when you inject it. ArteFill is available in a 0.8-ml or 0.4-ml syringe, and is sold in a box with three syringes that are 0.8 ml and three that are 0.4 ml.AdvantagesArteFill is a permanent substance. It contains lidocaine and isn’t painful for the patient. Because it includes a collagen, there is less bruising than with hyaluronic acids. The interesting thing about ArteFill is the 5-year data. Not only is the substance still there, but there’s improvement in the correction after 1 year.DisadvantagesThe fact that ArteFill is a permanent substance is both an advantage and a disadvantage. It also must be refrigerated, and patients must undergo a skin test and wait 4 weeks before undergoing treatment.