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 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 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 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.
Artecoll 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.
Autologen 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.
Dermalogen 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 Cymetra
AlloDerm 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.
Isolagen 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 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 Perlane
Restylane is manufactured by Medicis.
Restylane is an FDA-approved nonanimal-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.
Radiesse 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 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-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.
Silicone 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-FDAapproved indications unless under a formal investigational protocol.
Sculptra 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 nonanimal-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.
Gore-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.
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:
- Bleeding or bruising: Patients should discontinue aspirin and other blood thinners, nonsteroidal anti-inflammatory drugs (NSAIDs), vitamin E, and alcohol prior to therapy. An ice pack should be applied to the area to be treated before and after the injection to enhance vasoconstriction.
- Bacterial infection: Pain and/or erythema starting 24-72 hours after treatment and escalating thereafter may herald infection. Patients should be monitored if appropriate, culturing should be obtained, and oral antibiotics should immediately be started.
- Viral infection, including activation of herpes simplex: Administration of prophylactic antiviral therapy is prudent in those patients who report recrudescent herpes simplex or zoster periorally more than 6 times a year.
- Allergic reactions: Skin testing procedures recommended by the manufacturer of the particular product should always be followed to minimize the risk of allergic reactions. Systemic or intralesional steroids are often used if sensitivity occurs. Topical tacrolimus and systemic cyclosporine have been reported to be helpful in collagen hypersensitivity. Time yields improvement in biodegradable injectables.
- Superficial beading of overlying skin: This complication usually resolves spontaneously but can be disturbing to the patient. Lancing the overlying skin with a 19-gauge needle and expressing the excess material can often correct this problem. Superficial beading should resolve with time.
Serious complications include the following:
- Rarely, death (eg, secondary to anaphylactic shock or sepsis)
- Anaphylactic reactions
- Blindness secondary to thrombus formation in the retinal artery after arterial injection periorbitally or from needle trauma: The use of higher viscosity materials (eg, Zyplast, Cymetra) should be avoided near the eyes or in the glabellar region. The needle should always be directed away from the eye.
- Local skin necrosis secondary to occlusion of cutaneous arterioles: This complication can be recognized early as vasoconstriction (blanching) and pain at the injection site. Immediate administration of heat, massage, and nitroglycerin paste can help to minimize or reverse permanent injury.
- Cystic reactions to implanted material or foreign body abscesses: These reactions are usually treated with incision and drainage and intralesional steroids.
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.