- Email: [email protected]
Facial filler agents
Operative Techniques in Otolaryngology (2007) 18, 243-247
Facial filler agents Raghu S. Athre, MD From Premier Image Cosmetic and Laser Surgery Center, Atlanta, Georgia. KEYWORDS Facial filler; Facial aging; Hyaluronic acid; Collagen; Soft tissue
Facial filling agents can successfully be used to combat facial aging. In the past few years, multiple new agents have been introduced into the marketplace. This article will briefly introduce the options with respect to filling agents and describe their uses. © 2007 Elsevier Inc. All rights reserved.
Rejuvenation of the aging face has always been an integral part of facial plastic surgery. The aging face is characterized by macroscopic and microscopic changes. Some of the macroscopic changes include the formation of jowls, melolabial folds, and tear-trough deformities. Other changes in facial appearance include bone and soft-tissue volume depletion, changes in skin quality, and the downward gravitational pull of facial musculature and soft tissue. Large macroscopic changes can be counteracted by surgery, such as facelifts and midface lifts. Filler agents have a specific role in combating facial aging changes to augment surgical results and offer real benefits in patients with lesser degrees of aging not yet conducive to invasive procedures.
Anatomy of skin Human skin is a stratified structure composed of layers. The superficial most layer is the epidermis, which serves as a barrier to the outside environment. The dermis lies under the epidermis and consists of 2 layers, the papillary dermis and the reticular dermis. Under the dermis lies the subcutis, which consists of fat and adds volume. Collagen is the principal building block of skin. In the papillary dermis, collagen forms a fine mesh of fibers that ties the epidermis down to the underlying dermis. This meshwork is composed of primarily type 3 collagen.1 In the reticular dermis, collagen forms thick bundles. In contrast to the papillary dermis, the primary type of collagen in the Address reprint requests and correspondence: Raghu S. Athre, MD, Premier Image Cosmetic and Laser Surgery Center, 4553 N. Shallowford Lane #20B, Atlanta, GA 30338. E-mail address: [email protected]. 1043-1810/$ -see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.otot.2007.07.002
reticular dermis is type 1 collagen. Type 1 collagen makes up 80% of the total collagen in skin by weight.1 Elastic fibers also are found in the skin and contribute to skin’s resilience. Elastic fibers contribute to less than 3% of dermis by dry weight. The final component to the dermis is ground substance. Ground substance fills in the spaces between the cellular and fibrous components of dermis and is composed of glycosaminoglycans, urionic acids, and plasma proteins.2 Glycosaminoglycans have a complex chemical structure that allows them to attract and hold water, sometimes in amounts up to 1000 times their own volume.2 As aging occurs, the amount of collagen in skin decreases. The ratio of type 1 to type 3 collagen also decreases.1 Furthermore, exposure to tobacco smoke and excessive sun damage can increase tissue collagenase levels and decrease tissue collagen. Macroscopically, this leads to loss of skin turgor, skin elasticity, and the development of wrinkles and sagging.3
Facial filling There are numerous locations in which dermal filling agents can be injected in the aging face. It might almost be described as: “Where there’s a hole or a ditch, fill it!” Common locations for filling include: ● ● ● ● ● ●
The glabellar region for lateral crows feet that might be persistent after Botox administration; Lower eyelid/cheek complex to fill tear trough; Malar soft-tissue augmentation to mask volume loss; Melolabial folds; Lip augmentation; Marionette lines;
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Circumferential perioral rhytids; Temporal area for temporal wasting; and Soft-tissue augmentation to mask hemifacial asymmetries (ie, facial nerve paralysis with loss of facial muscle bulk).
Temporary filler agents Collagen replacement Because the primary problem with age-related changes of the skin is a loss of tissue collagen, it follows that replacement of the collagen would combat the problem. Cosmoderm, Cosmoplast, Zyderm, and Zyplast (all from INAMED Aesthetics, Irvine, CA) are all collagen replacements. Zyderm and Zyplast are bovine collagen products derived from cowhides from an isolated U.S. herd of cows.4 Zyderm was first introduced into the market in 1976 and was approved by the Food and Drug Administration (FDA) for facial lines and wrinkles in 1981. Zyplast followed by being approved by the FDA in 1985. Zyplast was developed to provide a longer-lasting result than Zyderm. Zyderm is available in 2 forms: Zyderm 1 (3.5% collagen) and Zyderm 2 (6.5% collagen). The difference between Zyderm and Zyplast is that Zyplast is cross-linked with gluteraldehyde to prevent breakdown by tissue collagenases.3 This cross-linkage allows Zyplast to last slightly longer comparison with Zyderm.3 Because these products are derived from bovine collagen, skin testing is necessary to check for an allergic reaction.5 A small skin inoculation of the product should be performed before injecting these products into the face. Some practitioners recommend a second skin test before injecting the face because the first skin test may act as a sensitizing event.5 It is imperative to note that allergic reactions to bovine collagen can develop after multiple injections.5 Zyderm 1 is injected into the superficial papillary dermis, Zyderm 2 is injected into the mid-dermis, and Zyplast is injected into the deep reticular dermis.4 Because Zyderm 1 and 2 are buffered in saline, overcorrection is necessary. Zyderm 1 requires 100% overcorrection, and Zyderm 2 requires 50% overcorrection.4 This overcorrection is to combat the fact that the saline used to buffer the collagen will be absorbed first and might result in an incomplete correction of the void if overcorrection is not performed. Zyplast, in contrast, does not require overcorrection. The injected collagen material is eventually cleared by a foreignbody, inflammatory response.4 The average length of correction is 4 to 5 months in the nasolabial folds and 2 to 3 months in the lips.4 Cosmoderm and Cosmoplast are human-derived collagen products. These products are derived from fibroblast cell lines.6 The primary advantage to these products is that skin testing is not required because the products are humanderived. Like Zyplast, Cosmoplast is cross-linked with gluteraldehyde to down-regulate destruction by tissue collagenases. These products are easier to use than bovine collagen, but their duration of action is less.4
Hyaluronic acid As explained previously, hyaluronic acid is component of the interstitial matrix of the dermis. It provides a gelatinous matrix in which elastic fibers are suspended.7 A major advantage of hyaluronic acid over collagen is that the structure of hyaluronic acid is more uniform across various animal species. This decreases the immunogenicity of hyaluronic acid. The chemical structure of hyaluronic acid allows the influx and retention of large amounts of water. Older skin has less hyaluronic acid and, therefore, less hydration and turgor. Hyaluronic acid in native form is not a viable filler agent because of its short half-life (⬃20 hours). To increase duration of action, hyaluronic acid formulations are crosslinked. Cross-linked formulations are called hylans. As described previously, hyaluronic acid is extremely hydrophilic and retains a significant amount of water. Hylans share this property. Hylans also have some unique characteristics that make them ideal filler agents. Hylans exhibit dynamic viscosity, which essentially states that the viscosity of the hylan is inversely proportional to the shear force on the hylan.8 An example of this occurs during injection. In the needle, the hylan filler agent is exposed to a great deal of shear force. Therefore, its viscosity decreases to allow for easy passage through the syringe and needle. However, once injected, the filler agent is not exposed to any shear force. Therefore, the viscosity of the hylan increases to prevent migration within the tissue. Another unique characteristic of hylan filler agents is isovolemic degradation.8 As hyaluronic acid particles in the injected matrix degrade, other hyaluronic acid particles in the matrix bind more water to keep the volume of the injected matrix the same. It is not until the last hyaluronic acid particle is degraded that the injected matrix volume decreases. This translates to more consistent filling of defects rather than a constant decrease in filled volume over the lifespan of the implanted matrix.8 Multiple hyaluronic acid filler agents are approved by the FDA and available in the United States. Restylane (Medicis Aesthetics, Inc, Scottsdale, AZ) is a hyaluronic acid filler derived from Streptococcus cultures and is cross-linked with epoxides.9 Restylane has approximately 400 m-sized particles and has a concentration of 20 mg/mL.9 Restylane has 2 alternative formulations: Restylane Fine Lines and Restylane Perlane. The concentration of all 3 formulations is 20 mg/mL. The difference between the 3 formulations is particle size. Restylane Fine Lines has the smallest particle size, and Perlane has the largest particle size. Having larger particle sizes translates to longevity of effect.9 Hylaform (INAMED Aesthetics) is the next hyaluronic acid filler agent. It is derived from rooster combs.8 Hylaform has a small amount of avian protein and hence may trigger allergic reactions. In contrast to Restylane, Hylaform has a decreased concentration of hyaluronic acid (5.5 mg/mL versus 20 mg/mL) and has a greater degree of cross-linking (20% versus ⬍1%). These factors result in a shortened lifespan in comparison to Restylane.10 Hylaform Plus has a larger particle size (750 versus 500 m) and is injected deeper into the dermis.
Athre
Facial Filler Agents
Captique (INAMED Aesthetics) is a nonanimal-derived hyaluronic acid filler produced by bacterial fermentation. Like Hylaform, Captique is also 5.5 mg/mL and 20% crosslinked. Juvederm (INAMED Aesthetics) is a bacterially derived hyaluronic acid filler that is a homogenous gel rather than particles within a matrix. The result is that Juvederm is more biocompatible, and should last longer.7 Hyaluronic acid fillers are injected intradermally. Too deep an injection can decrease the duration of result, and too superficial an injection can lead to unappealing lumps and bumps. If injected too superficially, or if the result of injection is not desirable, hyaluronidase can be injected to degrade the filler, rather than waiting for the body to resorb the filler agent. Hyaluronic acid preparations are not combined with lidocaine. As a result, local blocks may be necessary for anesthesia. Injections should correct 100% of the defect, and no overcorrection is necessary. Duration of effects ranges between 6 to 9 months, and re-injecting patients who have had full correction of a defect requires less filler agent than the initial correction.9
Autogenous fat Autogenous fat has one main advantage over all other filler materials: Because it is autogenously derived, there is no chance of rejection or allergic reaction. It is also easily harvested via liposuction of the thighs, abdomen, or buttocks. Some of the primary disadvantages of fat include the fact that (1) all of the other filler agents are easily injected in the office setting; (2) the need to harvest the fat usually requires a trip to the operating room, thereby increasing the time and cost of the injection; and (3) harvesting of fat can be difficult in the very thin patient. The primary disadvantage of fat is the unpredictability with respect to duration of effect. Some studies have shown that fat’s effect may be permanent. This is seldom the case in the author’s experience. It is true that nondynamic sites such as the melolabial folds do have a longer duration of effect than dynamic sites such as the glabella.4
Cymetra Cymetra (LifeCell Corporation, Branchburg, NJ) is a micronized form of Alloderm. Alloderm is an acellular dermal tissue product from human donors. This tissue product consists of collagen, proteoglycans, and essentially all the components of normal dermal tissue with the exception of cells. When injected, this material forms a bio-framework for fibroblasts and other cells to aggregate and promote tissue ingrowth. It is packaged as a powder and is reconstituted with saline or lidocaine before injection. Its longevity is approximately 3 to 6 months, but results are variable.5
245 is the same compound used to make the absorbable suture Vicryl.11 It is approved by the FDA for correction of HIVassociated lipoatrophy, especially in the temporal area. It essentially is a large area corrective agent, and is not useful for correcting fine lines and rhytids. Application of Sculptra for facial rejuvenation is an off-label use of the product. Sculptra is available as a powder and must be reconstituted with 3 to 5 mL of sterile water or lidocaine at least 2 hours before injection. This time period is required to ensure full hydration of the product. The poly-L-lactic acid particles are small enough to be injected through a 26-gauge needle, but large enough to prevent phagocytosis on transmigration through capillary walls.11 Sculptra is usually injected into the subcutaneous tissues. The initial filling of the area is secondary to the mechanical influx of the injected agent. This result is transient because the poly-L-lactic acid particles are decomposed by the body. However, the filling agent triggers ingrowth of collagen, which ultimately results in the permanent filling effect. Because the filling effect is not completely predictable, it is important to not overcorrect. Long-term volume correction requires several months and most likely several touch-up sessions. Sequential injections are usually spaced 4 to 6 weeks apart. Postinjection massage of the area is recommended. The long-term volume augmentation lasts 18 to 24 months.
Radiesse Radiesse (BioForm Medical, San Mateo, CA) is an FDAapproved filler consisting of calcium hydroxyapatite spheres. Calcium hydroxyapatite is the mineral component of bone and is therefore well tolerated by the body. The injected spheres range from 25 to 45 m in size and promote collagen ingrowth to achieve volume augmentation. The product is extremely viscous and should therefore be injected in the deep dermis or subdermally. After injection, massage is necessary to contour the product.12 Long-term volume augmentation is achieved by 2 mechanisms. The carrier material is slowly degraded over a time course of 6 to 8 weeks. However, collagen ingrowth replaces the lost volume secondary to carrier degradation resulting in volume augmentation.8 Also, a localized fibroblastic reaction encapsulates the hydroxyapatite particles to prevent migration.12 These encapsulated particles also help augment volume. During a period of many years, the hydroxyapatite will degrade to calcium and phosphate ions. However, radiographic evidence of implant material persists for at least 6 years with no evidence of calcification or neoossification.12 Palpability of the implant is normal for 2 to 3 months after injection and is caused by the increased viscosity of the implant in contrast to the surrounding tissue. This will soften as the carrier material is resorbed and collage fills the area.
Semipermanent filler agents ArteFill Sculptra Sculptra (Dermik Laboratories, Berwyn, PA) is a synthetic, nonanimal-derived polymer of poly-L-lactic acid and
ArteFill (Artes Medical, San Diego, CA) is an FDAapproved product composed of 20% polymethylmethacrylate microspheres and 80% bovine collagen.13 The bovine
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collagen acts as a delivery agent for the microspheres and has been chemically altered to reduce antigenicity. However, despite this, skin allergy testing is still required.4 The collagen component of the filler implant is degraded in approximately 4 months. However, the microspheres will last forever. Long-term volume augmentation is achieved by tissue inflammation that encapsulates the microspheres. The degree of the connective tissue reaction is variable, and cannot be predicted. Younger individuals have a greater amount of connective tissue response than older individuals. This connective tissue response leads to approximately 50% to 75% permanent correction.4 It is important to counsel patients that correction of a defect will require multiple injections spaced over 3 to 4 months to achieve optimal results.4 Overcorrection should not be performed since the amount of connective tissue reaction cannot be predicted. Patients should be advised to minimize facial expression for 3 to 4 days following injection to prevent migration of the implant.8 This product has been available in Europe since 1993, and the collective experience shows long-term correction at greater than 10 years.
deep dermis, where less viscous agents and agents with smaller particle sizes are injected more superficially. An important caveat of this is that agents can be layered on top of each other for optimal results. Injecting the correct volume is also important in minimizing these minor complications. As described earlier, a unique characteristic of hyaluronic acid fillers is that problems with incorrect depth of injection, palpability, and lumpiness can be corrected by injecting hyaluronidase to degrade the filler agent. Major complications include allergic/hypersensitivity reactions and granuloma/nodule formation.15 Allergic reactions occur more commonly with animal-derived agents, but can occur with any of the agents listed. All of the agents listed elicit some degree of a connective tissue response.15 Although granuloma formation with the biologic products such as collagen and hyaluronic acid preparations is rare, it has been reported.16,17 Granuloma formation is more common with alloplastic materials such as the ArteFill.18,19 Treatment of granulomas and other foreign body reactions includes excision, incision/drainage, and usage of hyaluronidase in the case of hyaluronic acid fillers.17
Injectable silicone
Conclusions Silicone refers to polymers of silicon. Silicone has been used as a facial augmentation material for more than 40 years. However, silicone is not approved by the FDA for facial augmentation and usage for facial augmentation is considered an off-label use. Two forms of liquid silicone are commercially available: (1) Silikon (Alcon Laboratories, Fort Worth, TX), and (2) AdatoSil (Bausch & Lomb, Rochester, NY). They differ is viscosity with AdatoSil being more viscous. Silikon is preferred for facial augmentation. Silicone is the most permanent and least antigenic of the filler agents. Silicone is injected via the microdroplet technique. Small volumes (0.01-0.03 mL) of Silicone are injected in a grid-like fashion spaced at 1 to 3 mm into the deep dermis.14 Individual droplets disperse within the tissue and become fibro-encapsulated over the course of weeks. Multiple injections every 4 weeks are necessary to achieve the final result.14 Overcorrection is not necessary, and results may not be apparent for 2 to 3 treatments. Per the Soft Tissue Augmentation Task Force Report on Liquid Injectable Silicone for the American Academy of Dermatology in December 1993, “there is a wealth of clinical experience in dermatology with the use of liquid injectable silicone by the micro-droplet technique which shows its efficacy and safety in many individuals over many years.”
The arena of filler agents is in continual flux with new agents appearing daily. The past 2 decades have been peppered with the emergence of all of the aforementioned agents with the exception of collagen and silicone. As time passes, each new agent promises increased safety, better longevity, better tissue compatibility, and fewer complications. This work is meant as an introductory primer into the world of filler agents. It is by no means a replacement for training and experience. Permanent filler agents may be permanent, but their cosmetic result is not. Patients will continue to age, and the idea of esthetic beauty will continue to evolve. It is important for the clinician starting in this arena to gain experience with temporary fillers first, before going on to permanent agents. The use of dermal filling agents has drastically altered the face of facial plastic surgery by improving surgical results and as a stand-alone procedure. It is quick, efficacious, safe, and creates happy patients. It is definitely a tool to be mastered in the armamentarium of the facial plastic surgeon.
References Complications It is important to note that all procedures have associated complications. Usage of dermal filler agents is not exempt from this paradigm. Minor complications include palpability of the implant, skin changes, and excessive lumps. Injecting the agent at the correct depth can prevent most of these complications. This monograph details the correct depth for each agent. As a rule, more viscous agents and agents with large particle sizes should be injected into the
1. Arndt KA, LeBoit PE, Robinson JK, et al: What is normal skin? in White CR Jr, Bigby M, Sangueza OP (eds): Cutaneous Medicine and Surgery: An Integrated Program in Dermatology, vol. 1. Philadelphia, W.B. Saunders Company, 1996 pp 3-45 2. Uitto J, Bernstein EF, McGrath JA. The dermis, in White CR Jr, Bigby M, Sangueza OP (eds): Cutaneous Medicine and Surgery: An Integrated Program in Dermatology, vol. 1. Philadelphia, W.B. Saunders Company, 1996 pp 857-881 3. Bauman L: CosmoDerm/CosmoPlast (human bioengineered collagen) for the aging face. Facial Plast Surg 20:125-128, 2004 4. Murray CA, Zloty D, Warshawski L: The evolution of soft tissue fillers in clinical practice. Dermatol Clin 23:343-363, 2005
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5. Owens JM: Soft tissue implants and fillers. Otolaryngol Clin N Am 38:361-369, 2005 6. Glavas IP: Filling agents. Ophthalmol Clin North Am 18:249-257, 2005 7. Baumann L: Replacing dermal constituents lost through aging with dermal fillers. Semin Cutan Med Surg 23:160-166, 2004 8. Narins RS, Bowman PH: Injectable skin fillers. Clin Plast Surg 32: 151-162, 2005 9. Matarasso SL, Carruthers JD, Jewell ML, for the Restylane Consensus Group: Consensus recommendations for soft-tissue augmentation with nonanimal stabilized hyaluronic acid (Restylane). Plast Reconstr Surg 117:3S-34S, 2006 (suppl) 10. Rao J, Chi GC, Goldman MP: Clinical comparison between two hyaluronic acid-derived fillers in the treatment of nasolabial folds: Hylaform versus restylane. Dermatol Surg 31:1587-1590, 2005 11. Vleggaar D: Facial volumetric correction with injectable poly-L-lactic acid. Dermatol Surg 2005;31:1511-1518 12. Flaharty P: Radiance. Facial Plast Surg 20:165-169, 2004
247 13. Thaler MP, Ubogy ZI: Artecoll: The Arizona experience and lessons learned. Dermatol Surg 31:1566-1576, 2005 14. Duffy DM: Liquid silicone for soft tissue augmentation. Dermatol Surg 31:1530-1541, 2005 15. Zimmerman U, Clerici TJ: The histologic aspects of fillers complications. Semin Cutan Med Surg 23:241-250, 2004 16. Brody HJ: Use of hyaluronidase in the treatment of granulomatous acid reactions or unwanted hyaluronic acid placement. Dermatol Surg 31:893-897, 2005 17. Hönig JF, Brink U, Korabiowski M: Severe granulomatous allergic tissue reaction after hyaluronic acid injection in the treatment of facial lines and its surgical correction. J Craniofac Surg 14:197-200, 2003 18. Lombardi T, Samson J, Plantier F, et al: Orofacial granulomas after injection of cosmetic fillers: Histopathologic and clinical study of 11 cases. J Oral Pathol Med 23:115-120, 2004 19. Parada MB, Michalany NS, Hassun KM, et al: A histologic study of adverse effects of different cosmetic skin fillers. Skinmed 4:345-349, 2005
Facial filler agents Raghu S. Athre, MD From Premier Image Cosmetic and Laser Surgery Center, Atlanta, Georgia. KEYWORDS Facial filler; Facial aging; Hyaluronic acid; Collagen; Soft tissue
Facial filling agents can successfully be used to combat facial aging. In the past few years, multiple new agents have been introduced into the marketplace. This article will briefly introduce the options with respect to filling agents and describe their uses. © 2007 Elsevier Inc. All rights reserved.
Rejuvenation of the aging face has always been an integral part of facial plastic surgery. The aging face is characterized by macroscopic and microscopic changes. Some of the macroscopic changes include the formation of jowls, melolabial folds, and tear-trough deformities. Other changes in facial appearance include bone and soft-tissue volume depletion, changes in skin quality, and the downward gravitational pull of facial musculature and soft tissue. Large macroscopic changes can be counteracted by surgery, such as facelifts and midface lifts. Filler agents have a specific role in combating facial aging changes to augment surgical results and offer real benefits in patients with lesser degrees of aging not yet conducive to invasive procedures.
Anatomy of skin Human skin is a stratified structure composed of layers. The superficial most layer is the epidermis, which serves as a barrier to the outside environment. The dermis lies under the epidermis and consists of 2 layers, the papillary dermis and the reticular dermis. Under the dermis lies the subcutis, which consists of fat and adds volume. Collagen is the principal building block of skin. In the papillary dermis, collagen forms a fine mesh of fibers that ties the epidermis down to the underlying dermis. This meshwork is composed of primarily type 3 collagen.1 In the reticular dermis, collagen forms thick bundles. In contrast to the papillary dermis, the primary type of collagen in the Address reprint requests and correspondence: Raghu S. Athre, MD, Premier Image Cosmetic and Laser Surgery Center, 4553 N. Shallowford Lane #20B, Atlanta, GA 30338. E-mail address: [email protected]. 1043-1810/$ -see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.otot.2007.07.002
reticular dermis is type 1 collagen. Type 1 collagen makes up 80% of the total collagen in skin by weight.1 Elastic fibers also are found in the skin and contribute to skin’s resilience. Elastic fibers contribute to less than 3% of dermis by dry weight. The final component to the dermis is ground substance. Ground substance fills in the spaces between the cellular and fibrous components of dermis and is composed of glycosaminoglycans, urionic acids, and plasma proteins.2 Glycosaminoglycans have a complex chemical structure that allows them to attract and hold water, sometimes in amounts up to 1000 times their own volume.2 As aging occurs, the amount of collagen in skin decreases. The ratio of type 1 to type 3 collagen also decreases.1 Furthermore, exposure to tobacco smoke and excessive sun damage can increase tissue collagenase levels and decrease tissue collagen. Macroscopically, this leads to loss of skin turgor, skin elasticity, and the development of wrinkles and sagging.3
Facial filling There are numerous locations in which dermal filling agents can be injected in the aging face. It might almost be described as: “Where there’s a hole or a ditch, fill it!” Common locations for filling include: ● ● ● ● ● ●
The glabellar region for lateral crows feet that might be persistent after Botox administration; Lower eyelid/cheek complex to fill tear trough; Malar soft-tissue augmentation to mask volume loss; Melolabial folds; Lip augmentation; Marionette lines;
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Circumferential perioral rhytids; Temporal area for temporal wasting; and Soft-tissue augmentation to mask hemifacial asymmetries (ie, facial nerve paralysis with loss of facial muscle bulk).
Temporary filler agents Collagen replacement Because the primary problem with age-related changes of the skin is a loss of tissue collagen, it follows that replacement of the collagen would combat the problem. Cosmoderm, Cosmoplast, Zyderm, and Zyplast (all from INAMED Aesthetics, Irvine, CA) are all collagen replacements. Zyderm and Zyplast are bovine collagen products derived from cowhides from an isolated U.S. herd of cows.4 Zyderm was first introduced into the market in 1976 and was approved by the Food and Drug Administration (FDA) for facial lines and wrinkles in 1981. Zyplast followed by being approved by the FDA in 1985. Zyplast was developed to provide a longer-lasting result than Zyderm. Zyderm is available in 2 forms: Zyderm 1 (3.5% collagen) and Zyderm 2 (6.5% collagen). The difference between Zyderm and Zyplast is that Zyplast is cross-linked with gluteraldehyde to prevent breakdown by tissue collagenases.3 This cross-linkage allows Zyplast to last slightly longer comparison with Zyderm.3 Because these products are derived from bovine collagen, skin testing is necessary to check for an allergic reaction.5 A small skin inoculation of the product should be performed before injecting these products into the face. Some practitioners recommend a second skin test before injecting the face because the first skin test may act as a sensitizing event.5 It is imperative to note that allergic reactions to bovine collagen can develop after multiple injections.5 Zyderm 1 is injected into the superficial papillary dermis, Zyderm 2 is injected into the mid-dermis, and Zyplast is injected into the deep reticular dermis.4 Because Zyderm 1 and 2 are buffered in saline, overcorrection is necessary. Zyderm 1 requires 100% overcorrection, and Zyderm 2 requires 50% overcorrection.4 This overcorrection is to combat the fact that the saline used to buffer the collagen will be absorbed first and might result in an incomplete correction of the void if overcorrection is not performed. Zyplast, in contrast, does not require overcorrection. The injected collagen material is eventually cleared by a foreignbody, inflammatory response.4 The average length of correction is 4 to 5 months in the nasolabial folds and 2 to 3 months in the lips.4 Cosmoderm and Cosmoplast are human-derived collagen products. These products are derived from fibroblast cell lines.6 The primary advantage to these products is that skin testing is not required because the products are humanderived. Like Zyplast, Cosmoplast is cross-linked with gluteraldehyde to down-regulate destruction by tissue collagenases. These products are easier to use than bovine collagen, but their duration of action is less.4
Hyaluronic acid As explained previously, hyaluronic acid is component of the interstitial matrix of the dermis. It provides a gelatinous matrix in which elastic fibers are suspended.7 A major advantage of hyaluronic acid over collagen is that the structure of hyaluronic acid is more uniform across various animal species. This decreases the immunogenicity of hyaluronic acid. The chemical structure of hyaluronic acid allows the influx and retention of large amounts of water. Older skin has less hyaluronic acid and, therefore, less hydration and turgor. Hyaluronic acid in native form is not a viable filler agent because of its short half-life (⬃20 hours). To increase duration of action, hyaluronic acid formulations are crosslinked. Cross-linked formulations are called hylans. As described previously, hyaluronic acid is extremely hydrophilic and retains a significant amount of water. Hylans share this property. Hylans also have some unique characteristics that make them ideal filler agents. Hylans exhibit dynamic viscosity, which essentially states that the viscosity of the hylan is inversely proportional to the shear force on the hylan.8 An example of this occurs during injection. In the needle, the hylan filler agent is exposed to a great deal of shear force. Therefore, its viscosity decreases to allow for easy passage through the syringe and needle. However, once injected, the filler agent is not exposed to any shear force. Therefore, the viscosity of the hylan increases to prevent migration within the tissue. Another unique characteristic of hylan filler agents is isovolemic degradation.8 As hyaluronic acid particles in the injected matrix degrade, other hyaluronic acid particles in the matrix bind more water to keep the volume of the injected matrix the same. It is not until the last hyaluronic acid particle is degraded that the injected matrix volume decreases. This translates to more consistent filling of defects rather than a constant decrease in filled volume over the lifespan of the implanted matrix.8 Multiple hyaluronic acid filler agents are approved by the FDA and available in the United States. Restylane (Medicis Aesthetics, Inc, Scottsdale, AZ) is a hyaluronic acid filler derived from Streptococcus cultures and is cross-linked with epoxides.9 Restylane has approximately 400 m-sized particles and has a concentration of 20 mg/mL.9 Restylane has 2 alternative formulations: Restylane Fine Lines and Restylane Perlane. The concentration of all 3 formulations is 20 mg/mL. The difference between the 3 formulations is particle size. Restylane Fine Lines has the smallest particle size, and Perlane has the largest particle size. Having larger particle sizes translates to longevity of effect.9 Hylaform (INAMED Aesthetics) is the next hyaluronic acid filler agent. It is derived from rooster combs.8 Hylaform has a small amount of avian protein and hence may trigger allergic reactions. In contrast to Restylane, Hylaform has a decreased concentration of hyaluronic acid (5.5 mg/mL versus 20 mg/mL) and has a greater degree of cross-linking (20% versus ⬍1%). These factors result in a shortened lifespan in comparison to Restylane.10 Hylaform Plus has a larger particle size (750 versus 500 m) and is injected deeper into the dermis.
Athre
Facial Filler Agents
Captique (INAMED Aesthetics) is a nonanimal-derived hyaluronic acid filler produced by bacterial fermentation. Like Hylaform, Captique is also 5.5 mg/mL and 20% crosslinked. Juvederm (INAMED Aesthetics) is a bacterially derived hyaluronic acid filler that is a homogenous gel rather than particles within a matrix. The result is that Juvederm is more biocompatible, and should last longer.7 Hyaluronic acid fillers are injected intradermally. Too deep an injection can decrease the duration of result, and too superficial an injection can lead to unappealing lumps and bumps. If injected too superficially, or if the result of injection is not desirable, hyaluronidase can be injected to degrade the filler, rather than waiting for the body to resorb the filler agent. Hyaluronic acid preparations are not combined with lidocaine. As a result, local blocks may be necessary for anesthesia. Injections should correct 100% of the defect, and no overcorrection is necessary. Duration of effects ranges between 6 to 9 months, and re-injecting patients who have had full correction of a defect requires less filler agent than the initial correction.9
Autogenous fat Autogenous fat has one main advantage over all other filler materials: Because it is autogenously derived, there is no chance of rejection or allergic reaction. It is also easily harvested via liposuction of the thighs, abdomen, or buttocks. Some of the primary disadvantages of fat include the fact that (1) all of the other filler agents are easily injected in the office setting; (2) the need to harvest the fat usually requires a trip to the operating room, thereby increasing the time and cost of the injection; and (3) harvesting of fat can be difficult in the very thin patient. The primary disadvantage of fat is the unpredictability with respect to duration of effect. Some studies have shown that fat’s effect may be permanent. This is seldom the case in the author’s experience. It is true that nondynamic sites such as the melolabial folds do have a longer duration of effect than dynamic sites such as the glabella.4
Cymetra Cymetra (LifeCell Corporation, Branchburg, NJ) is a micronized form of Alloderm. Alloderm is an acellular dermal tissue product from human donors. This tissue product consists of collagen, proteoglycans, and essentially all the components of normal dermal tissue with the exception of cells. When injected, this material forms a bio-framework for fibroblasts and other cells to aggregate and promote tissue ingrowth. It is packaged as a powder and is reconstituted with saline or lidocaine before injection. Its longevity is approximately 3 to 6 months, but results are variable.5
245 is the same compound used to make the absorbable suture Vicryl.11 It is approved by the FDA for correction of HIVassociated lipoatrophy, especially in the temporal area. It essentially is a large area corrective agent, and is not useful for correcting fine lines and rhytids. Application of Sculptra for facial rejuvenation is an off-label use of the product. Sculptra is available as a powder and must be reconstituted with 3 to 5 mL of sterile water or lidocaine at least 2 hours before injection. This time period is required to ensure full hydration of the product. The poly-L-lactic acid particles are small enough to be injected through a 26-gauge needle, but large enough to prevent phagocytosis on transmigration through capillary walls.11 Sculptra is usually injected into the subcutaneous tissues. The initial filling of the area is secondary to the mechanical influx of the injected agent. This result is transient because the poly-L-lactic acid particles are decomposed by the body. However, the filling agent triggers ingrowth of collagen, which ultimately results in the permanent filling effect. Because the filling effect is not completely predictable, it is important to not overcorrect. Long-term volume correction requires several months and most likely several touch-up sessions. Sequential injections are usually spaced 4 to 6 weeks apart. Postinjection massage of the area is recommended. The long-term volume augmentation lasts 18 to 24 months.
Radiesse Radiesse (BioForm Medical, San Mateo, CA) is an FDAapproved filler consisting of calcium hydroxyapatite spheres. Calcium hydroxyapatite is the mineral component of bone and is therefore well tolerated by the body. The injected spheres range from 25 to 45 m in size and promote collagen ingrowth to achieve volume augmentation. The product is extremely viscous and should therefore be injected in the deep dermis or subdermally. After injection, massage is necessary to contour the product.12 Long-term volume augmentation is achieved by 2 mechanisms. The carrier material is slowly degraded over a time course of 6 to 8 weeks. However, collagen ingrowth replaces the lost volume secondary to carrier degradation resulting in volume augmentation.8 Also, a localized fibroblastic reaction encapsulates the hydroxyapatite particles to prevent migration.12 These encapsulated particles also help augment volume. During a period of many years, the hydroxyapatite will degrade to calcium and phosphate ions. However, radiographic evidence of implant material persists for at least 6 years with no evidence of calcification or neoossification.12 Palpability of the implant is normal for 2 to 3 months after injection and is caused by the increased viscosity of the implant in contrast to the surrounding tissue. This will soften as the carrier material is resorbed and collage fills the area.
Semipermanent filler agents ArteFill Sculptra Sculptra (Dermik Laboratories, Berwyn, PA) is a synthetic, nonanimal-derived polymer of poly-L-lactic acid and
ArteFill (Artes Medical, San Diego, CA) is an FDAapproved product composed of 20% polymethylmethacrylate microspheres and 80% bovine collagen.13 The bovine
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collagen acts as a delivery agent for the microspheres and has been chemically altered to reduce antigenicity. However, despite this, skin allergy testing is still required.4 The collagen component of the filler implant is degraded in approximately 4 months. However, the microspheres will last forever. Long-term volume augmentation is achieved by tissue inflammation that encapsulates the microspheres. The degree of the connective tissue reaction is variable, and cannot be predicted. Younger individuals have a greater amount of connective tissue response than older individuals. This connective tissue response leads to approximately 50% to 75% permanent correction.4 It is important to counsel patients that correction of a defect will require multiple injections spaced over 3 to 4 months to achieve optimal results.4 Overcorrection should not be performed since the amount of connective tissue reaction cannot be predicted. Patients should be advised to minimize facial expression for 3 to 4 days following injection to prevent migration of the implant.8 This product has been available in Europe since 1993, and the collective experience shows long-term correction at greater than 10 years.
deep dermis, where less viscous agents and agents with smaller particle sizes are injected more superficially. An important caveat of this is that agents can be layered on top of each other for optimal results. Injecting the correct volume is also important in minimizing these minor complications. As described earlier, a unique characteristic of hyaluronic acid fillers is that problems with incorrect depth of injection, palpability, and lumpiness can be corrected by injecting hyaluronidase to degrade the filler agent. Major complications include allergic/hypersensitivity reactions and granuloma/nodule formation.15 Allergic reactions occur more commonly with animal-derived agents, but can occur with any of the agents listed. All of the agents listed elicit some degree of a connective tissue response.15 Although granuloma formation with the biologic products such as collagen and hyaluronic acid preparations is rare, it has been reported.16,17 Granuloma formation is more common with alloplastic materials such as the ArteFill.18,19 Treatment of granulomas and other foreign body reactions includes excision, incision/drainage, and usage of hyaluronidase in the case of hyaluronic acid fillers.17
Injectable silicone
Conclusions Silicone refers to polymers of silicon. Silicone has been used as a facial augmentation material for more than 40 years. However, silicone is not approved by the FDA for facial augmentation and usage for facial augmentation is considered an off-label use. Two forms of liquid silicone are commercially available: (1) Silikon (Alcon Laboratories, Fort Worth, TX), and (2) AdatoSil (Bausch & Lomb, Rochester, NY). They differ is viscosity with AdatoSil being more viscous. Silikon is preferred for facial augmentation. Silicone is the most permanent and least antigenic of the filler agents. Silicone is injected via the microdroplet technique. Small volumes (0.01-0.03 mL) of Silicone are injected in a grid-like fashion spaced at 1 to 3 mm into the deep dermis.14 Individual droplets disperse within the tissue and become fibro-encapsulated over the course of weeks. Multiple injections every 4 weeks are necessary to achieve the final result.14 Overcorrection is not necessary, and results may not be apparent for 2 to 3 treatments. Per the Soft Tissue Augmentation Task Force Report on Liquid Injectable Silicone for the American Academy of Dermatology in December 1993, “there is a wealth of clinical experience in dermatology with the use of liquid injectable silicone by the micro-droplet technique which shows its efficacy and safety in many individuals over many years.”
The arena of filler agents is in continual flux with new agents appearing daily. The past 2 decades have been peppered with the emergence of all of the aforementioned agents with the exception of collagen and silicone. As time passes, each new agent promises increased safety, better longevity, better tissue compatibility, and fewer complications. This work is meant as an introductory primer into the world of filler agents. It is by no means a replacement for training and experience. Permanent filler agents may be permanent, but their cosmetic result is not. Patients will continue to age, and the idea of esthetic beauty will continue to evolve. It is important for the clinician starting in this arena to gain experience with temporary fillers first, before going on to permanent agents. The use of dermal filling agents has drastically altered the face of facial plastic surgery by improving surgical results and as a stand-alone procedure. It is quick, efficacious, safe, and creates happy patients. It is definitely a tool to be mastered in the armamentarium of the facial plastic surgeon.
References Complications It is important to note that all procedures have associated complications. Usage of dermal filler agents is not exempt from this paradigm. Minor complications include palpability of the implant, skin changes, and excessive lumps. Injecting the agent at the correct depth can prevent most of these complications. This monograph details the correct depth for each agent. As a rule, more viscous agents and agents with large particle sizes should be injected into the
1. Arndt KA, LeBoit PE, Robinson JK, et al: What is normal skin? in White CR Jr, Bigby M, Sangueza OP (eds): Cutaneous Medicine and Surgery: An Integrated Program in Dermatology, vol. 1. Philadelphia, W.B. Saunders Company, 1996 pp 3-45 2. Uitto J, Bernstein EF, McGrath JA. The dermis, in White CR Jr, Bigby M, Sangueza OP (eds): Cutaneous Medicine and Surgery: An Integrated Program in Dermatology, vol. 1. Philadelphia, W.B. Saunders Company, 1996 pp 857-881 3. Bauman L: CosmoDerm/CosmoPlast (human bioengineered collagen) for the aging face. Facial Plast Surg 20:125-128, 2004 4. Murray CA, Zloty D, Warshawski L: The evolution of soft tissue fillers in clinical practice. Dermatol Clin 23:343-363, 2005
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Facial Filler Agents
5. Owens JM: Soft tissue implants and fillers. Otolaryngol Clin N Am 38:361-369, 2005 6. Glavas IP: Filling agents. Ophthalmol Clin North Am 18:249-257, 2005 7. Baumann L: Replacing dermal constituents lost through aging with dermal fillers. Semin Cutan Med Surg 23:160-166, 2004 8. Narins RS, Bowman PH: Injectable skin fillers. Clin Plast Surg 32: 151-162, 2005 9. Matarasso SL, Carruthers JD, Jewell ML, for the Restylane Consensus Group: Consensus recommendations for soft-tissue augmentation with nonanimal stabilized hyaluronic acid (Restylane). Plast Reconstr Surg 117:3S-34S, 2006 (suppl) 10. Rao J, Chi GC, Goldman MP: Clinical comparison between two hyaluronic acid-derived fillers in the treatment of nasolabial folds: Hylaform versus restylane. Dermatol Surg 31:1587-1590, 2005 11. Vleggaar D: Facial volumetric correction with injectable poly-L-lactic acid. Dermatol Surg 2005;31:1511-1518 12. Flaharty P: Radiance. Facial Plast Surg 20:165-169, 2004
247 13. Thaler MP, Ubogy ZI: Artecoll: The Arizona experience and lessons learned. Dermatol Surg 31:1566-1576, 2005 14. Duffy DM: Liquid silicone for soft tissue augmentation. Dermatol Surg 31:1530-1541, 2005 15. Zimmerman U, Clerici TJ: The histologic aspects of fillers complications. Semin Cutan Med Surg 23:241-250, 2004 16. Brody HJ: Use of hyaluronidase in the treatment of granulomatous acid reactions or unwanted hyaluronic acid placement. Dermatol Surg 31:893-897, 2005 17. Hönig JF, Brink U, Korabiowski M: Severe granulomatous allergic tissue reaction after hyaluronic acid injection in the treatment of facial lines and its surgical correction. J Craniofac Surg 14:197-200, 2003 18. Lombardi T, Samson J, Plantier F, et al: Orofacial granulomas after injection of cosmetic fillers: Histopathologic and clinical study of 11 cases. J Oral Pathol Med 23:115-120, 2004 19. Parada MB, Michalany NS, Hassun KM, et al: A histologic study of adverse effects of different cosmetic skin fillers. Skinmed 4:345-349, 2005