You are in: eMedicine Specialties > Dermatology > SURGICAL Dermal FillersArticle Last Updated: Feb 7, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 8
  Author: Roberta D Sengelmann, MD, Director, Center for Dermatologic and Cosmetic Surgery, Assistant Professor, Department of Medicine, Divisions of Dermatology and Otolaryngology, Washington University School of Medicine Roberta D Sengelmann is a member of the following medical societies: American Academy of Cosmetic Surgery, American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American Medical Association, and American Society for Dermatologic Surgery Coauthor(s): Stacey S Tull, MD, MPH, Assistant Professor, Divison of Dermatology, Washington University School of Medicine/Barnes Jewish Hospital Editors: Shobana Sood, MD, Assistant Professor, Department of Dermatology, University of Pennsylvania Hospital; Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center; John G Albertini, MD, Consulting Staff, Dermatologic Surgery, The Skin Surgery Center; Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System Author and Editor Disclosure Synonyms and related keywords: dermal filling agents, injectable dermal fillers, dermal implants, facial implants, bovine collagen, soft-tissue augmentation, soft tissue augmentation, autologous collagen, treatment for rhytids INTRODUCTIONSection 2 of 8
  Along with a trend toward living a longer, healthier life, more and more patients are looking to physicians to help them achieve a more youthful appearance. The skin's natural aging process manifests as contour changes and rhytids secondary to the depletion of subcutaneous fat and the loss of dermal collagen. Traditionally, rejuvenation has been achieved with a face-lift by surgically tightening the skin. Today, a multitude of minimally invasive procedures are aimed at rejuvenation without the risk, recovery time, and expense of major surgery. The development and popularity of BOTOX® has opened the door for equally noninvasive, adjunctive treatment of dynamic rhytids. Soft tissue augmentation has become a popular means of addressing contour defects that result from aging, photodamage, trauma and/or scarification, or disease. Dozens of filling agents exist in the armamentarium; therefore, the physician is responsible for knowing which substance is best suited to address a particular defect and the patient. In this article, an overview of dermal filling agents, which are used for more superficial contour irregularities, is provided. Subcutaneous soft tissue augmentation, including autologous fat transfer, is covered in another article. BACKGROUND AND HISTORYSection 3 of 8
Although humans have been practicing the art of tissue augmentation since ancient times and despite a renaissance in implant technology in the last several decades, to date no perfect substance for soft tissue augmentation exists. A consensus exists on the properties of the ideal dermal filler; these properties include the following:
Modern soft tissue augmentation dates back to the late 19th century when Neuber first used autologous fat to correct depressed facial defects. Shortly thereafter, in the early 1900s, injectable paraffin gained popularity until a high incidence of foreign body granuloma formation was discovered. In the 1940s, the use of highly refined injectable silicone emerged as a dermal implant, with excellent cosmetic results and high use potential. However, because of the high abuse potential and untoward adverse effects from adulterated compounds, its use as a cosmetic agent has been banned. The last several decades have seen an explosion in technologic advances contributing to a cascade of new dermal implants. Injectable bovine collagen was developed in the 1970s. Approved by the FDA in 1981, it has remained the industry criterion standard. In the 1980s, Fibrel was introduced and then approved by the FDA for dermal augmentation. Fibrel works by forming a clot, which, in turn, stimulates collagen synthesis. In the face of the AIDS epidemic and a concern for blood-borne diseases, the company later pulled Fibrel off the market, reconsidering the use of human serum for product reconstitution. With the emergence of liposuction in the late 1970s, fat once again became a convenient source for tissue augmentation. In the late 1980s, autologous collagen processed from harvested fat was first used for dermal augmentation. The most recent advances in dermal filling technology are in the form of hyaluronic acid derivatives, harvested and cultured autologous dermal implants, allogeneic products, and synthetically derived products. Continuing research promises that advances, such as recombinant human collagen, are on the horizon. TYPES OF DERMAL FILLERSSection 4 of 8
Bovine collagenBovine collagen is manufactured by INAMED (formerly McGhan Medical Corporation). Bovine collagen was the first legally approved product for soft tissue augmentation in the United States, and it remains the criterion standard against which all other dermal implants are measured. Results can last 3-18 months, although in the authors' experience, repeat treatment is usually required at 3-5 months. Three forms of sterile, purified, fibrillar collagen include Zyderm I, Zyderm II, and Zyplast. These forms are derived from the hides of isolated herds of domestic cattle, thereby negating the possibility of contamination with the bovine spongiform encephalopathy virus or prion that causes mad cow disease. Zyderm I Zyderm I contains 95-98% type I collagen, and the remainder is type III collagen. It also contains 0.3% lidocaine. Zyderm is 3.5% bovine dermal collagen by weight suspended in physiologic phosphate-buffered sodium chloride solution. Zyderm is injected into the papillary dermis for treatment of superficial rhytids, including those around the eyes, lips, and glabellar region; it is also used in acne scars and lip augmentation. Overcorrection by approximately 100% is required secondary to absorption. Zyderm II Zyderm II is identical to Zyderm I except that it is 6.5% bovine dermal collagen by weight. Zyderm II is injected into the shallow reticular dermis for more coarse rhytids as well as for acne scars and lip augmentation. Less overcorrection (approximately 50%) is required than Zyderm I because of a higher concentration of collagen and slower resorption. Zyplast Zyplast is 3.5% bovine dermal collagen cross-linked by glutaraldehyde to form a latticework and a more viscous compound. Zyplast is less immunogenic than Zyderm I or Zyderm II, and it is more resistant to degradation. Zyplast is injected into the mid to deep reticular dermis for treatment of deeper rhytids and contour defects, including nasolabial folds, marionette lines, and significant lip augmentation. No overcorrection required. Zyplast should not be used in the glabellar region because of possible local tissue necrosis. It is often layered with Zyderm I or Zyderm II for more dramatic, longer-lasting results. As many as 5% of patients may experience hypersensitivity to injectable bovine collagen. For this reason, skin testing is required before treatment. Two skin tests performed 2 weeks apart, with the last test at least 4 weeks before treatment, is now standard. A positive test result is defined as erythema, induration, tenderness, or swelling that persists for more than 6 hours after implantation. Despite negative test results, INAMED states that fewer than 3% of patients undergoing treatment develop an allergic reaction. If hypersensitivity occurs, it is usually within 1-2 weeks of treatment. It manifests as erythema and induration, with or without pruritus in the area treated. Treatment for hypersensitivity may include topical tacrolimus 0.1% twice daily, systemic cyclosporine, systemic steroids, intralesional steroids, and time. Long-term or systemic sequelae are unknown, if any exist at all. Contraindications to using injectable bovine collagen include a history of an anaphylactic event of any cause, previous sensitivity to bovine collagen, lidocaine sensitivity, pregnancy, and active infection at the treatment site. Although no formal testing has been completed, INAMED states that patients undergoing hormonal fluctuation, such as that in pregnancy or during menopause, may have an increased risk for hypersensitivity. Cosmoderm and Cosmoplast Cosmoderm and Cosmoplast are manufactured by INAMED. Cosmoderm and Cosmoplast are FDA-approved fillers consisting of natural human collagen grown under controlled laboratory conditions. Pretreatment skin tests are not necessary, and the materials are screened for purity. Both products contain 35 mg/mL of human-derived collagen in phosphate-buffered physiological saline containing 0.3% lidocaine. Cosmoderm is not cross-linked and is used to treat superficial lines and wrinkles, whereas Cosmoplast is cross-linked with glutaraldehyde and can be used for deeper wrinkles. Because skin testing is not necessary and because these products are associated with virtually no risk of causing a hypersensitivity reaction, Cosmoderm and Cosmoplast have become the criterion standard for collagen products, replacing the former standard Zyderm/Zyplast. Autologous collagenAutologous collagen works by promoting an inflammatory response that, in turn, results in the deposition of new collagen at the recipient site. Harvested autologous fat from procedures, such as liposuction, is processed by mixing it with sterile distilled water and then by allowing it to freeze, thereby leading to the rupture of adipocytes. The liquefied fraction of intracellular triglycerides is then ready to be injected through a fine-gauge needle (eg, 30-gauge needle) suitable for intradermal injection. This technique is often used in conjunction with subcutaneous fat transplantation. The benefit of this technique is its autologous nature, negating the need for hypersensitivity testing. However, it requires harvesting the tissue from a donor site as well as involved preparation and expedient administration after harvesting the tissue. Studies vary on the duration of autologous collagen; the range is months to years, depending on the methods used in fat harvesting, processing, and transplanting. ArtecollArtecoll is manufactured by Rofil Medical International. It is marketed in Canada. Artecoll is not FDA approved in the United States. Artecoll consists of polymethylmethacrylate microspheres suspended in bovine collagen. The collagen serves as a vehicle for injection and is eventually degraded, leaving behind permanent implantation of the beads. The mixture is injected without overcorrection at the dermal-subdermal junction to treat deeper rhytids and scars. Sixty-five percent of patients report results after 2 years. Patients must be tested for allergy to bovine collagen prior to administration. The company recommends a single skin test 14-21 days prior to treatment. Contraindications to using Artecoll include sensitivity to bovine collagen; history of keloids; history of atrophic skin diseases; and patients with thin, flaccid skin because of the risk of permanent surface irregularities. AutologenAutologen is manufactured by Collagenesis Corporation. Autologen is a sterile suspension of collagen fibers prepared from the patient's tissue. Three square inches of harvested skin are sent to the manufacturer and yield 1 mL of approximately 3.5% collagen. Autologen is injected into the superficial mid dermis to treat fine lines, wrinkles, scars, and lip atrophy. Autologen has been reported to have as much as 75% persistence at 1 year. The benefits of Autologen are that it does not require skin testing and that it lasts longer than bovine collagen. The main drawbacks are that it involves dermal harvesting from a donor site and that it requires careful timing of the procedure since it must be used within several hours of delivery. However, if the patient is undergoing a surgical procedure, excess skin can be stored at the manufacturer (for a fee) for future processing. DermalogenDermalogen was also manufactured by Collagenesis; however, because of corporate turnover and loss of acquisition, Dermalogen has not been manufactured since the fall of 2001. The same technology was used in processing Dermalogen and Autologen. Dermalogen is a human tissue collagen matrix derived from cadaveric dermis suspended in a neutral pH buffer that contains matrix proteins, such as elastin and ground substance components. The donated skin is subject to the same stringent screening overseen by the American Association of Tissue Banks (AATB). Like Autologen, Dermalogen did not require skin testing and was identical in composition and administration. It served as an alternative for patients who are allergic to bovine collagen, those who are not undergoing elective surgical procedures that yield excess skin, and those who are not satisfied with other agents. Additionally, unlike Autologen, it was more economical and more readily available because processing time was not required. However, Dermalogen was more painful during injection because it lacked lidocaine. Persistence of Dermalogen correction was reported at as much as 50% at 1 year. Although the company that manufactured Dermalogen claimed that no skin test was needed, nonspecific inflammation and foreign body reactions at the site of administration were reported in the literature. Whether these adverse effects were true hypersensitivity reactions is not clear. AlloDerm and CymetraAlloDerm and Cymetra are manufactured by LifeCell Corporation. AlloDerm is acellular human cadaveric dermis that has been freeze-dried. AlloDerm is processed as sheets and was widely used in the treatment of full-thickness burns and blistering conditions, such as epidermolysis bullosa. It is also used in soft tissue augmentation procedures, such as rhinoplasty, lip augmentation, glabellar contouring, and scar revision. Screening and collection is subject to the AATB guidelines, and the product is processed for purity. AlloDerm is surgically implanted in a sterile field under local or general anesthesia. Significant swelling can occur in the first postoperative week. Results last 6-12 months in most patients but have been known to persist for several years. Cymetra is the micronized, injectable form of AlloDerm. It is reconstituted in the physician's office with lidocaine. Like AlloDerm, no allergy testing is required according to the manufacturer, and no known hypersensitivity to the product has been reported. Cymetra is injected into the dermis just over the dermal-subcutaneous junction to treat deeper rhytids and acne scars. It is also used in lip augmentation, producing a smooth result. Even though the manufacturer has addressed difficulties in reconstituting the product, because of a lumpy and viscous material, a 23- or 26-gauge needle is often required for injection, which necessitates local or regional anesthesia. According to the company, results typically last 3-6 months. Contraindications to using AlloDerm or Cymetra include allergy to gentamicin, collagen vascular disease, and avascular or infected recipient site. The authors do not recommend the use of Cymetra in the glabellar region because of the risk of arterial occlusion. If injected periorbitally, these viscous soft tissue fillers can cause overcorrection, local skin necrosis, or retinal artery thrombosis. IsolagenIsolagen is manufactured by Isolagen Technologies Incorporated. Isolagen consists of cultured autologous fibroblasts. A 3-mm punch biopsy is obtained from the patient and then sent to the manufacturer to be grown in culture. The presence of growth factors used to culture the cells requires it to be regulated by the FDA; therefore, for now, the company has temporarily halted production and is not accepting biopsy samples from new patients. Clinical trials are underway that may eventually lead to FDA approval. Processing usually takes 6 weeks at which time a test dose is sent back to the physician to be administered to the patient. If no reaction occurs after 2 weeks, Isolagen can be administered. Isolagen needs to be injected into multiple levels of the dermis for best results in the treatment of rhytids and scars and for use in lip augmentation. Once received, the product must be administered within 24 hours, which can be a logistic challenge and an expensive waste if a patient or a physician cannot meet these time constraints. Two to three treatments have been shown to yield persistent therapeutic results for as long as 22 months. Hylaform gelHylaform gel is manufactured by INAMED and Genzyme Corporations. Hyaluronic acid is a polysaccharide found in the dermis of all mammals. Hylaform gel, previously known as Hylan B gel, is a form of cross-linked hyaluronic acid (5.5 mg/mL) derived from the rooster combs of domestic fowl. It is reported to be less immunogenic and longer lasting than bovine collagen. One study showed 86% histologic persistence of Hylaform gel compared with 25% of bovine collagen in guinea pigs at 26 weeks. Besides being longer lasting than collagen, proponents say it has less risk of clumping and goes in more smoothly. Overcorrection is not needed with this product. Although Hylaform gel is widely used throughout the world for dermal filling of scars and rhytids and in lip augmentation, and it has been recently approved in the United States. In the United States, it is approved for injection into the mid-to-deep dermis to correct soft tissue contour deficiencies (eg, wrinkles, acne scars). It is used in a more concentrated form, Synvisc, to treat osteoarthritis of the knee. Restylane and PerlaneRestylane is manufactured by Medicis. Restylane is an FDA-approved non–animal-stabilized hyaluronic acid derivative used for soft tissue augmentation. Unlike Hylaform gel, it is derived from streptococcal bacterial fermentation and does not require an animal source. At 20 mg/mL, Restylane has a higher concentration of hyaluronic acid than Hylaform gel. It is used to treat rhytids and scars and in lip augmentation. Restylane correction was noted to be 82% at 3 months and 33% at 1 year in a study involving 285 wrinkles treated in 113 patients. Perlane is also a hyaluronic acid derivative at 20 mg/mL, but it is a more robust form of Restylane for use in the deep dermis and at the dermal-fat junction. It is used in Canada but has not yet received FDA approval. Being hyaluronic acid derivatives similar to Hylaform Gel, Restylane and Perlane have less risk of clumping and go in more smoothly. Overcorrection is not needed with these products. However, neither product contains anesthetic and patients need to be treated with local anesthesia or regional blocks prior to administration. RadiesseRadiesse is manufactured by Bioform. Radiesse is composed of microspheres of calcium hydroxyl appetite suspended in an aqueous gel carrier. These biodegradable microspheres serve as a lattice upon which the body forms a scaffold for tissue infiltration. The spheres degrade slowly over years for a longer-lasting, semi-permanent effect. At this time, radiesse is approved by the FDA for such indications as bladder neck augmentation for urinary incontinence, vocal cord augmentation for paresis, and periodontal defects. Its use as a soft tissue filler is off-label, but this practice is common both abroad and in the United States, with a strong safety record. The most commonly treated areas are the nasolabial folds and marionette lines. Use for lip augmentation is discouraged because of the highly viscous nature of the product, which predisposes it to clumping in this area. Radiesse is completely biocompatible, with no need for pretreatment testing. The product does not contain anesthetic, so regional blocks are recommended. Reviderm intraReviderm intra is manufactured by Rofil Medical International. This product is not FDA approved in the United States. Reviderm intra consists of 40- to 60-µm dextran beads suspended in hylan gel of nonanimal origin. The proposed mechanism of action is an initial macrophage response followed by fibroblast proliferation and new collagen formation. Intradermal injection without overcorrection is used to treat rhytids and cutaneous defects (eg, atrophic scars), and, in the Netherlands, it is used in lip augmentation. One study of 274 patients reported permanent results. Endoplast-50Endoplast-50 is manufactured by Laboratories Filorgra. Currently, this product is only available in Europe and is not FDA approved in the United States. Endoplast-50 consists of solubilized elastin peptides with bovine collagen. Injected intradermally, the material influences the proliferation of fibroblasts to produce collagen. Two serial skin tests are required prior to treatment. Results are reported to last as long as 12 months. SiliconeSilicone is manufactured by Dow-Corning. Silicone for cosmetic or reconstructive use is not FDA approved in the United States. Silicones are a family of man-made polymers, which contain silica, and can exist as solids, gels, or liquids as a function of polymerization and cross-linkage. Highly refined liquid silicones have been used in treating superficial rhytids and scars and have the advantage of permanent correction. Unfortunately, because of the high abuse potential and numerous complications (eg, foreign body reactions, infections) as a result of adulterated compounds, the FDA has declared it illegal to use injectable silicone for tissue augmentation. Two forms of high-viscosity liquid silicone, Adatosil-5000 and Silikon-1000, are approved for use as ophthalmic devices. Despite legal ramifications, some physicians have used these forms of injectable silicone as facial dermal implants. Silicone products are not recommended to be used for non-FDA–approved indications unless under a formal investigational protocol. SculptraSculptra is manufactured by Dermik Aesthetics. Sculptra is poly-L-lactic acid is FDA approved for the treatment of HIV facial lipoatrophy. It serves as a volume enhancer and is used for indications similar to those for autologous fat transfer. Results are not immediate; treatment is performed as a series of 3-5 treatments approximately 1 month apart. New-fill is the name under which Sculptra is marketed in most countries outside the United States. New-fill is a non–animal-derived polylactic acid touted to be biocompatible, biodegradable, and immunologically inert. It is distributed freeze-dried, can be stored at room temperature, and is reconstituted with sterile water. New-fill is injected either into the superficial dermis for the treatment of rhytids and acne scars or subdermally to treat lipodystrophy of the cheeks and hands, liposuction contour deformities, and lip atrophy. Expanded polytetrafluoroethyleneGore-Tex, or expanded polytetrafluoroethylene (e-PTFE), is a specially prepared form of Teflon developed in the 1960s, and, in 1993, it was FDA approved for facial plastic and reconstructive surgery in the United States. SoftForm (manufactured by Collagen Aesthetics) and Ultrasoft (formerly Softform) are sheets, strips, and tubes of e-PTFE used as facial implants to treat depressed scars; lip atrophy; and deep furrows, such as nasolabial folds and marionette lines. Because the material is porous, it allows ingrowth of fibroblasts, thereby preventing migration and providing permanent correction. Because of the permanent nature of the implant, initially treating the patient with a temporary filler to ensure that he or she likes the result is advisable. Advanta is manufactured by Atrium Medical. This is a newer, dual-porosity e-PTFE implant design consists of a soft, high-porosity center integrated with a smooth, medium-porosity outer surface layer. Because of the softness and tissue integration of the implant, Advanta is considered a better alternative to the other e-PTFE implants, resulting in a softer, more biocompatible lip augmentation device. e-PTFE implants are generally used for deeper defects and, as such, are implanted just below the dermis at its junction with the fat. Formally, they are not dermal fillers, but because they are not reviewed in other articles, they are included here for thoroughness. COMPLICATIONSSection 5 of 8
Despite the minimally invasive nature of injectable dermal fillers, the potential for complications always exists and should be discussed with the patient prior to treatment. Common complications include the following:
Serious complications include the following:
Patients should expect to experience some degree of pain during injection, which varies for each product based on pH and whether the product is suspended or reconstituted in buffered lidocaine. Transient erythema can last as long as 36 hours after treatment, beyond which, hypersensitivity must be considered. Topical anesthetics and ice-cold compresses can be used to minimize the pain of injection. SUMMARYSection 6 of 8
The keys to a successful outcome in soft tissue augmentation are in knowing which implant best corrects a particular defect and in knowing how and when to intervene if adverse or unsatisfactory reactions occur. Of equal importance is the selection of a patient with reasonable expectations, with full disclosure of the risks. Consulting with the patient preoperatively is important to conduct a thorough history and physical examination, to discuss risks and benefits, to identify contraindications, and to review expectations and limitations. Nuances exist for each product, including level of pain upon injection, ease of use, location of injection into the skin, and duration of results, as well as potential risks and management of adverse sequelae. Although beyond the scope of this overview, prior to treating patients, the physician should thoroughly understand the chosen product and should have used it under the supervision of an experienced physician. MULTIMEDIASection 7 of 8
REFERENCESSection 8 of 8
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