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Soft Tissue Implants and Fillers
Otolaryngol Clin N Am 38 (2005) 361–369
Soft Tissue Implants and Fillers Jonathan M. Owens, MD Department of Otolaryngology-Head and Neck Surgery, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA
The modern cosmetic and reconstructive surgeon encounters many situations requiring augmentation of soft tissue of the head and neck. Most commonly, cosmetic concerns of patients necessitate use of such techniques. With the aging of the baby boomers and an ever-increasing societal pressure encouraging youthful appearance, facial rejuvenation has increased in popularity. Soft tissue augmentation is a critical component of comprehensive facial rejuvenation in areas such as the midface, lips, or areas of static skin lines. Implants have also been important complementary components in other aspects of facial cosmetic surgery, including rhinoplasty, lip augmentation, mentoplasty, and midface enhancement. Implants are used in other areas of otolaryngology, including laryngoplasty, ossiculoplasty, facial reanimation, mucosal grafting, and tympanoplasty. The ideal implant would be biologically inert, resemble tissue in its texture and pliability, possess longevity, be easily inserted and altered to the desired shape, create minimal morbidity at the insertion site or elsewhere, be minimally visible following placement, and be inexpensive. Such an implant has not been produced to date. To market a product as a medical implant or device in the United States, a manufacturer need not meet these criteria but must receive approval from the Food and Drug Administration (FDA) by filing for premarket approval. This approval simply confirms the safety of the device and its efficacy for the proposed applications. Long-term data regarding the true clinical utility of the device are generally not yet available upon approval for use. This information is attained through the combined experience of practicing clinicians and ultimately allows critical evaluation of the utility and merits of each particular implant. The past 2 decades have witnessed significant advances in the implants and fillers available to surgeons, particularly bioengineered autologous and allogeneic materials. Many different synthetic materials—polytetrafluoroethylene (Gore-Tex),
E-mail address: [email protected] 0030-6665/05/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.otc.2004.10.003
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silicone rubber (Silastic), silicone, hydroxyapatite—as well as biologic materials—collagen, hyaluronic acid, allogeneic dermis, autologous dermis, and collagen—have reached the marketplace. Experience with each type of implant has highlighted advantages and disadvantages that must be critically compared with regard to the situation at hand. The two main classes are solid implants and injectable fillers. Implants Autologous implants The use of autologous implants has been reported for more than 3 centuries, with the first report of calvarial bone grafting in 1670 [1]. Cartilage from septal, conchal, and costal sources has been used for nasal and auricular reconstruction. Bone from calvarium, iliac crest, and tibia has been incorporated in nasal and mandibular repair. Autologous fat has been used as an injectable implant in the face and in the larynx and for obliteration of the paranasal sinuses. The major drawback to autologous implants is the donor-site morbidity. Silicone Silicone is the polymer created from dimethylsiloxane subunits that can be vulcanized to create silicone rubber (Silastic). This product has been used for decades as a facial implant. Silastic typically has no pores, eliminating the possibility of fibrous ingrowth and blunting the inflammatory host response following implantation. Fenestrated implants contain pores that allow greater fibrous ingrowth, which prevents implant migration. Once in place, Silastic implants are difficult to palpate. Furthermore, complications such as bony erosion, infection, seroma, and extrusion, are quite rare. A wide variety of Silastic facial implants is marketed by many companies. These implants range from thin, conformable sheets used in middle ear surgery and for nasal dorsal augmentation to preshaped malar and mandibular implants. Silastic implants are also easily modified in the operating room to adapt to the shape desired for such applications as thyroplasty implants. Gore-Tex Gore-Tex is a product manufactured of expanded polytetrafluoroethylene. Gore-Tex, like Silastic, has been used successfully for decades, primarily for vascular graft implants. This material does possess pores, averaging approximately 22 lm, which allows limited fibrous ingrowth and incorporation into the implant while preventing significant inflammatory responses. The biocompatibility of Gore-Tex is excellent; low complication rates are associated with its use.
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The head and neck applications for which Gore-Tex has been used are similar to those of Silastic, including thyroplasty implants, nasolabial fold fillers, malar implants, and mandibular implants. AlloDerm AlloDerm (LifeCell Corp, Branchburg, New Jersey) is an acellular dermal graft product processed from cadaveric human skin. This material is processed by removing epithelial components, leaving the basement membrane intact. Dermal cells are then removed by a series of nondenaturing detergents while matrix degradation is prevented by inhibition of native metalloproteinases. This removal of cells limits the immunogenicity of the product, limiting rejection. The material is then freeze-dried in a manner that prevents damage to the collagen matrix. In the operating room, AlloDerm is rehydrated for 10 to 20 minutes in saline solution before use. Following implantation, host fibroblasts migrate to the graft and begin native collagen deposition. Angiogenesis also occurs, creating a vascular matrix. This remodeling process continues for up to 180 days as the host incorporates the graft into the healing wound. Volume loss has been noted, with 30% to 50% loss at 1 year reported [2]. The initial application of AlloDerm was in burn surgery, but it has found numerous otolaryngologic applications as well. Its use has been reported in parotidectomy [3] and facial defect repair [4], nasal dorsal augmentation [5], lip augmentation, mucosal grafting [6], tympanoplasty, nasal perforation repair [7], and static facial rehabilitation following facial paralysis [8].
MEDPOR MEDPOR (Porex, Newnan, Georgia) is an implantable, high-density polyethylene with large pores ([100 lm); the pore volume of the material is greater than 50%. This product is prepared as preformed implants or is available as a thin block that is easily fashioned to the appropriate dimensions in the operating room using standard surgical instruments. MEDPOR is typically placed subperiostially and may be secured in place with titanium screws, when possible, to prevent implant migration. The large pore size facilitates rapid tissue ingrowth and incorporation within the implant [9]. This incorporation has been reported to be hastened by impregnation of the implant with autologous blood clot before implantation [10]. Applications that have been reported for MEDPOR include orbital reconstruction, rhinoplasty, midfacial skeleton augmentation, cranioplasty, and auricular reconstruction. MEDPOR has also been used for laryngotracheoplasty in animal studies [11]. The complication rate associated with the use of MEDPOR is low, with fracture [12] and infection [13] being reported.
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Fillers Bovine collagen Bovine collagen has been used as an injectable filler for nearly 30 years [14]. The duration of effect from an injection of bovine collagen is typically less than 6 months. Zyderm (marketed by INAMED Aesthetics, formerly McGhan Medical, Santa Barabara, California) was the original injectable bovine collagen and was introduced in 1981. Zyderm was followed in 1985 by Zyplast, which was developed to provide a longer-lasting effect by crosslinking collagen fibrils with glutaraldehyde. Zyderm is packaged as ZydermI, a phosphate-buffered saline solution of 35 mg/mL of collagen with 0.3% lidocaine, and Zyderm-II, a concentration of 65 mg/mL of collagen with 0.3% lidocaine. Zyplast is similarly packaged with a concentration of 35 mg/ mL of collagen, also with 0.3% lidocaine. Skin testing is required before administration of these products, because 3% of the population will display a response to bovine collagen on skin challenge [15,16]. The response is typically a delayed hypersensitivity response, with erythema and wheal occurring 48 to 72 hours following exposure. Some sources even recommend a second skin test following a negative first test before initiating therapy, because 2% of patients will demonstrate hypersensitivity after repeat exposure despite initial nonreactivity [17]. It is also possible to develop hypersensitivity to bovine collagen following repeated injections, which must be monitored. Overcorrection of collagen to the target tissue is necessary to achieve a desired result, because loss of water from within the injected material occurs. This loss may be as much as 20% to 30%. Degradation and resorption of collagen are also common, so that repeat injections are typically required at 4- to 6-month intervals to maintain the desired effect. The applications described for bovine collagen injection are many. Correction of deep nasolabial folds, lip augmentation, and leveling of depressed facial scars are among those commonly reported. Hyaluronic acid Hyaluronic acid is a component of the proteoglycan portion of mesenchymal tissue. The substance is identical across all species and is therefore poorly immunogenic when used as an injectable filler. Skin testing, as required, for bovine collagen, is not necessary. Hylaform (INAMED, Santa Barbara, California) and Restylane (Q-Medical, Uppsala, Sweden) are two FDA-approved preparations of hyaluronic acid for soft tissue augmentation. Hylaform is produced from rooster combs and is a gel of hyaluronic acid with a small amount of avian protein. Hylaform is packaged in saline solution at a concentration of 5.5 mg/mL. Restylane is produced by bacteria in a biofermentation process and is packaged in a buffered solution at a concentration of 20 mg/mL.
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A recent randomized, double-blind comparison of Restylane and Zyplast for correction of nasolabial folds found the effect of Restylane to be more durable at 6 months follow-up, with no difference in the complication rates associated with the two products [18]. Furthermore, hyaluronic acid binds more water than collagen, resulting in less loss of injected volume with hyaluronic acid products than with collagen injections. Thus, the amount of overcorrection required to achieve desired results is less with hyaluronic acid injections than with collagen. The applications for injectable hyaluronic acid are similar to those of collagen, namely correction of deep facial folds and depressed scars.
Isolagen Isolagen (Isolagen Technologies, Houston, Texas) is a unique product based on injection of the patient’s own cells to correct a dermal defect. Isolagen is an injectable product consisting of autologous fibroblasts generated from a punch biopsy of postauricular skin using tissue culture techniques. The 3-mm punch biopsy is shipped on ice to the company for processing, which includes separation of native fibroblasts from the remainder of the tissue. The cells are then cultured and packaged as 1.0to 1.5-mL injectable fillers approximately 6 weeks later. Injection is usually performed on three occasions, 2 weeks apart, to correct facial lines, wrinkles, and scars. The fibroblasts generate new collagen in situ, correcting the imperfection of the injected area. An initial report of Isolagen included 10 patients, 9 of whom showed 60% to 100% improvement of the injected area at 6 months [19]. The authors also performed biopsies of injection sites before and after injection and noted significant increase in the density of dermal collagen [19]. A follow-up study of 94 patients revealed a 92% rate of patient satisfaction at 12 months and 70% satisfaction at 36 to 48 months [20]. Few adverse effects have been reported with Isolagen, because the material is autologous. The company reports a few cases of slight hypersensitivity to injection but no other adverse effects. Isolagen is not currently available in the United States. The FDA previously temporarily halted its review of the product after classifying the product as a medical device. Prospective, multicenter stage III trials are currently underway. The product is available in Europe, Asia, and Australia. Autologen Autologen (Collagenesis, Beverly, Massachusetts) is another product prepared from autologous tissue, with the injected product being a suspension of collagen. Autologen is prepared as a standard 4% solution in a phosphate buffer and also as Autologen XL, a 6% solution. Preparation
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of Autologen requires the harvest of donor skin, which is most commonly done in conjunction with other facial rejuvenation procedures such as blepharoplasty or rhytidectomy. This skin may be frozen for up to 2 weeks before shipment to the manufacturer. One mL of injectable final product can be obtained from 2 square inches of skin. As with Isolagen, several Autologen injections are often required to achieve the desired result, because a volume loss of 20% to 30% is noted following injection [21]. Loss of correction also occurs over time, with 50% correction noted at 6 months [22]. Autologen has been studied in comparison to injectable bovine collagen. The two products produce similar clinical and histologic results [23]. The autologous nature of Autologen eliminates the necessity of skin testing as required with bovine collagen. The cost and donor site morbidity are major limitations associated with this product. Dermalogen Homologous human collagen from banked donor tissue is also available as an injectable filler. Dermalogen (Collagenesis, Beverly, Massachusetts) is prepared similarly to Autologen but with banked donor skin serving as the source of material. The banked tissue is thoroughly screened for infectious contamination before processing. The product is available in 3.5% buffered solutions and is distributed in prepackaged syringes. The major advantage of homologous human collagen is that skin testing is not necessary as required with bovine collagen. Furthermore, Dermalogen has been shown to persist longer than injected bovine collagen at 12 weeks’ follow-up, but more local inflammation was noted with Dermalogen [24]. Overcorrection by 20% to 30% is recommended to achieve desired results given the resorption of the product over time. Dermalogen has been used as a dermal filler as well as an injected implant in vocal folds [25]. One reported foreign-body granulomatous response has been reported to Dermalogen [26]. Cymetra Cymetra is a micronized form of Alloderm; Cymetra is dried and packaged in 330-mg samples. The particles are resuspended in 1 mL of lidocaine or saline, depending on whether anesthesia is necessary for the application. The product closely resembles Dermalogen but also contains dermal elements in addition to collagens, including elastins and proteoglycans. Following injection, host fibroblasts and collagen are noted to infiltrate the implanted material [27]. The longevity of Cymetra has been noted to be greater than that of injected bovine collagen at 1 and 3 months [27]. Cymetra has been used as a dermal filler as well as for injection laryngoplasty [28]. Skin testing is not necessary when using Cymetra, and no adverse effects have been reported.
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Hydroxyapatite Hydroxyapatite, the mineral component of bone, has been engineered into various implant products, including ceramic implants, cement (BoneSource, Stryker, Kalamazoo, Michigan), and injectable microspheres (Radiesse, formerly Radiance, Bioform, San Mateo, California). Furthermore, otologic implants of hydroxyapatite have been in use for many years. BoneSource is packaged as a powder that is resuspended in saline to create a putty that can then be formed to the desired configuration. The putty forms a stable shape in 20 minutes and sets completely at 4 to 6 hours. The implant is converted to new bone rather than being resorbed over time, a process termed ‘‘osseoconversion’’ [29]. Radiesse is a product consisting of calcium hydroxyapatite spheres ranging 25 to 45 lm in diameter suspended in an aqueous gel, along with glycerin and sodium carboxycellulose. It may be applied to an open defect or injected into soft tissue. This injectable microsphere formulation has been shown to experience little migration following implantation and has a texture resembling native soft tissue [30]. The biocompatibility of hydroxyapatite products is excellent, with little to no inflammatory response noted at the implant site [29]. Applications for hydroxyapatite include cranioplasty and midface reconstruction, frontal sinus obliteration, soft tissue defect augmentation, laryngoplasty, and ossiculoplasty. The duration of effect of hydroxyapatite implants varies with the use. For cranioplasty the reconstruction is long-lived, with osseoconversion noted; with the injectable form, results are noted to last at least 2 years [30]. Summary The number and variety of soft tissue implants and fillers at the clinician’s disposal continues to increase rapidly as new materials and bioengineering techniques evolve. The ideal implant for all purposes does not yet exist, so the clinician must be familiar with a wide variety of products for each application. Continued advances in synthetic, allogeneic, and autologous products and experience with existing products will further augment the surgeon’s armamentarium in the coming years. References [1] Van Meekren J. Observation medicohisurgicae. Amsterdam: Henrici and T. Bloom; 1670. [2] Terion EO. AlloDerm acellular dermal graft: applications in esthetic and reconstructive soft tissue augmentation. In: Klein AW, editor. Tissue augmentation in clinical practice: procedures and techniques. New York: Dekker; 1998. p. 349–77. [3] Chao C, Freidman C, Alford E, et al. Acellular dermal allograft prevents postparotidectomy soft tissue defects: a preliminary experience. Journal of Otorhinolaryngology Head and Neck 1999;2:1–6.
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[4] Achauer BM, VanderKam VM, Celikoz B, et al. Augmentation of facial soft-tissue defects with AlloDerm dermal graft. Ann Plast Surg 1998;41:503–7. [5] Jackson IT, Yavuzer R. AlloDerm for dorsal nasal irregularities. Plast Reconstr Surg 2001; 107:553–8. [6] Rhee PH, Friedman CD, Ridge JA, et al. The use of processed allograft dermal matrix for intraoral resurfacing: an alternative to split-thickness skin grafts. Arch Otolaryngol Head Neck Surg 1998;124:1201–4. [7] Cohen NA, Mirza N. Acellular human dermal allograft in repair of unilateral partialthickness and full-thickness nasal septal mucosal defects. Laryngoscope 2000;110:2005–8. [8] Winslow CP, Wang TD, Wax MK. Static reanimation of the paralyzed face with an acellular dermal allograft sling. Arch Facial Plast Surg 2001;3:55–7. [9] Niechajev I. Porous polyethylene implants for nasal reconstruction: clinical and histologic studies. Aesthetic Plast Surg 1999;23:395–402. [10] Sabini P, Sclafani AP, Romo T, et al. Modulation of tissue ingrowth into porous highdensity polyethylene implants with basic fibroblast growth factor and autologous blood clot. Arch Facial Plast Surg 2000;2:27–33. [11] Hashem FK, Al Homsi M, Mahasin ZZ, et al. Laryngotracheoplasty using the Medpor implant: an animal model. J Otolaryngol 2001;30:334–9. [12] Ozturk S, Sengezer M, Coskun U, et al. An unusual complication of a Medpor implant in nasal reconstruction: a case report. Aesthetic Plast Surg 2002;26:419–22. [13] You JR, Seo JH, Kim YH, et al. Six cases of bacterial infection in porous orbital implants. Jpn J Ophthalmol 2003;47:512–8. [14] Knapp TR, Kaplan EN, Daniels JR. Injectable collagen for soft tissue augmentation. Plast Reconstr Surg 1977;60:389–405. [15] Framer FM, Churukium MM. Clinical use of injectable collagen: a three-year retrospective review. Arch Otolaryngol 1984;110:93–8. [16] Cooperman LS, Mackinnon V, Bechler G, et al. Injectable collagen: a six-year clinical investigation. Aesthetic Plast Surg 1985;9:145–51. [17] Stegman S, Chu S, Armstrong R. Adverse reactions to bovine collagen implant: clinical and histologic features. J Dermatol Surg Oncol 1988;14(Suppl):39–48. [18] Narins RS, Brandt F, Leyden J, et al. A randomized, double-blind, multicenter comparison of the efficacy and tolerability of restylane versus Zyplast for the correction of nasolabial folds. Dermatol Surg 2003;29:588–95. [19] Watson D, Keller GS, Lacombe V, et al. Autologous fibroblasts for treatment of facial rhytids and dermal depressions. Arch Facial Plast Surg 1999;1:165–70. [20] Boss WK, Usal H, Fodor PB, et al. Autologous cultured fibroblasts: a protein repair system. Ann Plast Surg 2000;44:536–42. [21] Fagien S. Facial soft-tissue augmentation with injectable autologous and allogeneic human tissue collagen matrix (Autologen and Dermalogen). Plast Reconstr Surg 2000; 105:362–73. [22] DeVore DP, Kelman CD, Fagien S, et al. Autologen: autologous, injectable dermal collagen. In: Bosniak S, editor. Principles and practice of ophthalmic plastic and reconstructive surgery. Philadelphia: WB Saunders; 1995. p. 650–75. [23] Sclafani AP, Romo T, Parker A, et al. Autologous collagen dispersion (Autologen) as a dermal filler: clinical observations and histologic findings. Arch Facial Plast Surg 2000; 2:48–52. [24] Sclafani AP, Romo T, Parker A, et al. Homologous collagen dispersion (Dermalogen) as a dermal filler: persistence and histology compared with bovine collagen. Ann Plast Surg 2002;49:181–8. [25] Courey MS. Homologous collagen substances for vocal fold augmentation. Laryngoscope 2001;111:747–58. [26] Moody BR, Sengelmann RD. Self-limited adverse reaction to human-derived collagen injectable product. Dermatol Surg 2000;26:936–8.
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[27] Sclafani AP, Romo T, Jacono AA, et al. Evaluation of acellular dermal graft in sheet (AlloDerm) and injectable (micronized AlloDerm) forms for soft tissue augmentation. Clinical observations and histological analysis. Arch Facial Plast Surg 2000;2:130–6. [28] Pearl AW, Woo P, Ostrowski R, et al. A preliminary report on micronized AlloDerm injection laryngoplasty. Laryngoscope 2002;112:990–6. [29] Friedman CD, Costantino PD, Takagi S, et al. BoneSource hydroxyapatite cement: a novel biomaterial for craniofacial skeletal tissue engineering and reconstruction. J Biomed Mater Res 1998;43:428–32. [30] Tzikas TL. Evaluation of the radiance FN soft tissue filler for facial soft tissue augmentation. Arch Facial Plast Surg 2004;6:234–9.
Soft Tissue Implants and Fillers Jonathan M. Owens, MD Department of Otolaryngology-Head and Neck Surgery, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA
The modern cosmetic and reconstructive surgeon encounters many situations requiring augmentation of soft tissue of the head and neck. Most commonly, cosmetic concerns of patients necessitate use of such techniques. With the aging of the baby boomers and an ever-increasing societal pressure encouraging youthful appearance, facial rejuvenation has increased in popularity. Soft tissue augmentation is a critical component of comprehensive facial rejuvenation in areas such as the midface, lips, or areas of static skin lines. Implants have also been important complementary components in other aspects of facial cosmetic surgery, including rhinoplasty, lip augmentation, mentoplasty, and midface enhancement. Implants are used in other areas of otolaryngology, including laryngoplasty, ossiculoplasty, facial reanimation, mucosal grafting, and tympanoplasty. The ideal implant would be biologically inert, resemble tissue in its texture and pliability, possess longevity, be easily inserted and altered to the desired shape, create minimal morbidity at the insertion site or elsewhere, be minimally visible following placement, and be inexpensive. Such an implant has not been produced to date. To market a product as a medical implant or device in the United States, a manufacturer need not meet these criteria but must receive approval from the Food and Drug Administration (FDA) by filing for premarket approval. This approval simply confirms the safety of the device and its efficacy for the proposed applications. Long-term data regarding the true clinical utility of the device are generally not yet available upon approval for use. This information is attained through the combined experience of practicing clinicians and ultimately allows critical evaluation of the utility and merits of each particular implant. The past 2 decades have witnessed significant advances in the implants and fillers available to surgeons, particularly bioengineered autologous and allogeneic materials. Many different synthetic materials—polytetrafluoroethylene (Gore-Tex),
E-mail address: [email protected] 0030-6665/05/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.otc.2004.10.003
oto.theclinics.com
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OWENS
silicone rubber (Silastic), silicone, hydroxyapatite—as well as biologic materials—collagen, hyaluronic acid, allogeneic dermis, autologous dermis, and collagen—have reached the marketplace. Experience with each type of implant has highlighted advantages and disadvantages that must be critically compared with regard to the situation at hand. The two main classes are solid implants and injectable fillers. Implants Autologous implants The use of autologous implants has been reported for more than 3 centuries, with the first report of calvarial bone grafting in 1670 [1]. Cartilage from septal, conchal, and costal sources has been used for nasal and auricular reconstruction. Bone from calvarium, iliac crest, and tibia has been incorporated in nasal and mandibular repair. Autologous fat has been used as an injectable implant in the face and in the larynx and for obliteration of the paranasal sinuses. The major drawback to autologous implants is the donor-site morbidity. Silicone Silicone is the polymer created from dimethylsiloxane subunits that can be vulcanized to create silicone rubber (Silastic). This product has been used for decades as a facial implant. Silastic typically has no pores, eliminating the possibility of fibrous ingrowth and blunting the inflammatory host response following implantation. Fenestrated implants contain pores that allow greater fibrous ingrowth, which prevents implant migration. Once in place, Silastic implants are difficult to palpate. Furthermore, complications such as bony erosion, infection, seroma, and extrusion, are quite rare. A wide variety of Silastic facial implants is marketed by many companies. These implants range from thin, conformable sheets used in middle ear surgery and for nasal dorsal augmentation to preshaped malar and mandibular implants. Silastic implants are also easily modified in the operating room to adapt to the shape desired for such applications as thyroplasty implants. Gore-Tex Gore-Tex is a product manufactured of expanded polytetrafluoroethylene. Gore-Tex, like Silastic, has been used successfully for decades, primarily for vascular graft implants. This material does possess pores, averaging approximately 22 lm, which allows limited fibrous ingrowth and incorporation into the implant while preventing significant inflammatory responses. The biocompatibility of Gore-Tex is excellent; low complication rates are associated with its use.
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The head and neck applications for which Gore-Tex has been used are similar to those of Silastic, including thyroplasty implants, nasolabial fold fillers, malar implants, and mandibular implants. AlloDerm AlloDerm (LifeCell Corp, Branchburg, New Jersey) is an acellular dermal graft product processed from cadaveric human skin. This material is processed by removing epithelial components, leaving the basement membrane intact. Dermal cells are then removed by a series of nondenaturing detergents while matrix degradation is prevented by inhibition of native metalloproteinases. This removal of cells limits the immunogenicity of the product, limiting rejection. The material is then freeze-dried in a manner that prevents damage to the collagen matrix. In the operating room, AlloDerm is rehydrated for 10 to 20 minutes in saline solution before use. Following implantation, host fibroblasts migrate to the graft and begin native collagen deposition. Angiogenesis also occurs, creating a vascular matrix. This remodeling process continues for up to 180 days as the host incorporates the graft into the healing wound. Volume loss has been noted, with 30% to 50% loss at 1 year reported [2]. The initial application of AlloDerm was in burn surgery, but it has found numerous otolaryngologic applications as well. Its use has been reported in parotidectomy [3] and facial defect repair [4], nasal dorsal augmentation [5], lip augmentation, mucosal grafting [6], tympanoplasty, nasal perforation repair [7], and static facial rehabilitation following facial paralysis [8].
MEDPOR MEDPOR (Porex, Newnan, Georgia) is an implantable, high-density polyethylene with large pores ([100 lm); the pore volume of the material is greater than 50%. This product is prepared as preformed implants or is available as a thin block that is easily fashioned to the appropriate dimensions in the operating room using standard surgical instruments. MEDPOR is typically placed subperiostially and may be secured in place with titanium screws, when possible, to prevent implant migration. The large pore size facilitates rapid tissue ingrowth and incorporation within the implant [9]. This incorporation has been reported to be hastened by impregnation of the implant with autologous blood clot before implantation [10]. Applications that have been reported for MEDPOR include orbital reconstruction, rhinoplasty, midfacial skeleton augmentation, cranioplasty, and auricular reconstruction. MEDPOR has also been used for laryngotracheoplasty in animal studies [11]. The complication rate associated with the use of MEDPOR is low, with fracture [12] and infection [13] being reported.
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Fillers Bovine collagen Bovine collagen has been used as an injectable filler for nearly 30 years [14]. The duration of effect from an injection of bovine collagen is typically less than 6 months. Zyderm (marketed by INAMED Aesthetics, formerly McGhan Medical, Santa Barabara, California) was the original injectable bovine collagen and was introduced in 1981. Zyderm was followed in 1985 by Zyplast, which was developed to provide a longer-lasting effect by crosslinking collagen fibrils with glutaraldehyde. Zyderm is packaged as ZydermI, a phosphate-buffered saline solution of 35 mg/mL of collagen with 0.3% lidocaine, and Zyderm-II, a concentration of 65 mg/mL of collagen with 0.3% lidocaine. Zyplast is similarly packaged with a concentration of 35 mg/ mL of collagen, also with 0.3% lidocaine. Skin testing is required before administration of these products, because 3% of the population will display a response to bovine collagen on skin challenge [15,16]. The response is typically a delayed hypersensitivity response, with erythema and wheal occurring 48 to 72 hours following exposure. Some sources even recommend a second skin test following a negative first test before initiating therapy, because 2% of patients will demonstrate hypersensitivity after repeat exposure despite initial nonreactivity [17]. It is also possible to develop hypersensitivity to bovine collagen following repeated injections, which must be monitored. Overcorrection of collagen to the target tissue is necessary to achieve a desired result, because loss of water from within the injected material occurs. This loss may be as much as 20% to 30%. Degradation and resorption of collagen are also common, so that repeat injections are typically required at 4- to 6-month intervals to maintain the desired effect. The applications described for bovine collagen injection are many. Correction of deep nasolabial folds, lip augmentation, and leveling of depressed facial scars are among those commonly reported. Hyaluronic acid Hyaluronic acid is a component of the proteoglycan portion of mesenchymal tissue. The substance is identical across all species and is therefore poorly immunogenic when used as an injectable filler. Skin testing, as required, for bovine collagen, is not necessary. Hylaform (INAMED, Santa Barbara, California) and Restylane (Q-Medical, Uppsala, Sweden) are two FDA-approved preparations of hyaluronic acid for soft tissue augmentation. Hylaform is produced from rooster combs and is a gel of hyaluronic acid with a small amount of avian protein. Hylaform is packaged in saline solution at a concentration of 5.5 mg/mL. Restylane is produced by bacteria in a biofermentation process and is packaged in a buffered solution at a concentration of 20 mg/mL.
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A recent randomized, double-blind comparison of Restylane and Zyplast for correction of nasolabial folds found the effect of Restylane to be more durable at 6 months follow-up, with no difference in the complication rates associated with the two products [18]. Furthermore, hyaluronic acid binds more water than collagen, resulting in less loss of injected volume with hyaluronic acid products than with collagen injections. Thus, the amount of overcorrection required to achieve desired results is less with hyaluronic acid injections than with collagen. The applications for injectable hyaluronic acid are similar to those of collagen, namely correction of deep facial folds and depressed scars.
Isolagen Isolagen (Isolagen Technologies, Houston, Texas) is a unique product based on injection of the patient’s own cells to correct a dermal defect. Isolagen is an injectable product consisting of autologous fibroblasts generated from a punch biopsy of postauricular skin using tissue culture techniques. The 3-mm punch biopsy is shipped on ice to the company for processing, which includes separation of native fibroblasts from the remainder of the tissue. The cells are then cultured and packaged as 1.0to 1.5-mL injectable fillers approximately 6 weeks later. Injection is usually performed on three occasions, 2 weeks apart, to correct facial lines, wrinkles, and scars. The fibroblasts generate new collagen in situ, correcting the imperfection of the injected area. An initial report of Isolagen included 10 patients, 9 of whom showed 60% to 100% improvement of the injected area at 6 months [19]. The authors also performed biopsies of injection sites before and after injection and noted significant increase in the density of dermal collagen [19]. A follow-up study of 94 patients revealed a 92% rate of patient satisfaction at 12 months and 70% satisfaction at 36 to 48 months [20]. Few adverse effects have been reported with Isolagen, because the material is autologous. The company reports a few cases of slight hypersensitivity to injection but no other adverse effects. Isolagen is not currently available in the United States. The FDA previously temporarily halted its review of the product after classifying the product as a medical device. Prospective, multicenter stage III trials are currently underway. The product is available in Europe, Asia, and Australia. Autologen Autologen (Collagenesis, Beverly, Massachusetts) is another product prepared from autologous tissue, with the injected product being a suspension of collagen. Autologen is prepared as a standard 4% solution in a phosphate buffer and also as Autologen XL, a 6% solution. Preparation
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of Autologen requires the harvest of donor skin, which is most commonly done in conjunction with other facial rejuvenation procedures such as blepharoplasty or rhytidectomy. This skin may be frozen for up to 2 weeks before shipment to the manufacturer. One mL of injectable final product can be obtained from 2 square inches of skin. As with Isolagen, several Autologen injections are often required to achieve the desired result, because a volume loss of 20% to 30% is noted following injection [21]. Loss of correction also occurs over time, with 50% correction noted at 6 months [22]. Autologen has been studied in comparison to injectable bovine collagen. The two products produce similar clinical and histologic results [23]. The autologous nature of Autologen eliminates the necessity of skin testing as required with bovine collagen. The cost and donor site morbidity are major limitations associated with this product. Dermalogen Homologous human collagen from banked donor tissue is also available as an injectable filler. Dermalogen (Collagenesis, Beverly, Massachusetts) is prepared similarly to Autologen but with banked donor skin serving as the source of material. The banked tissue is thoroughly screened for infectious contamination before processing. The product is available in 3.5% buffered solutions and is distributed in prepackaged syringes. The major advantage of homologous human collagen is that skin testing is not necessary as required with bovine collagen. Furthermore, Dermalogen has been shown to persist longer than injected bovine collagen at 12 weeks’ follow-up, but more local inflammation was noted with Dermalogen [24]. Overcorrection by 20% to 30% is recommended to achieve desired results given the resorption of the product over time. Dermalogen has been used as a dermal filler as well as an injected implant in vocal folds [25]. One reported foreign-body granulomatous response has been reported to Dermalogen [26]. Cymetra Cymetra is a micronized form of Alloderm; Cymetra is dried and packaged in 330-mg samples. The particles are resuspended in 1 mL of lidocaine or saline, depending on whether anesthesia is necessary for the application. The product closely resembles Dermalogen but also contains dermal elements in addition to collagens, including elastins and proteoglycans. Following injection, host fibroblasts and collagen are noted to infiltrate the implanted material [27]. The longevity of Cymetra has been noted to be greater than that of injected bovine collagen at 1 and 3 months [27]. Cymetra has been used as a dermal filler as well as for injection laryngoplasty [28]. Skin testing is not necessary when using Cymetra, and no adverse effects have been reported.
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Hydroxyapatite Hydroxyapatite, the mineral component of bone, has been engineered into various implant products, including ceramic implants, cement (BoneSource, Stryker, Kalamazoo, Michigan), and injectable microspheres (Radiesse, formerly Radiance, Bioform, San Mateo, California). Furthermore, otologic implants of hydroxyapatite have been in use for many years. BoneSource is packaged as a powder that is resuspended in saline to create a putty that can then be formed to the desired configuration. The putty forms a stable shape in 20 minutes and sets completely at 4 to 6 hours. The implant is converted to new bone rather than being resorbed over time, a process termed ‘‘osseoconversion’’ [29]. Radiesse is a product consisting of calcium hydroxyapatite spheres ranging 25 to 45 lm in diameter suspended in an aqueous gel, along with glycerin and sodium carboxycellulose. It may be applied to an open defect or injected into soft tissue. This injectable microsphere formulation has been shown to experience little migration following implantation and has a texture resembling native soft tissue [30]. The biocompatibility of hydroxyapatite products is excellent, with little to no inflammatory response noted at the implant site [29]. Applications for hydroxyapatite include cranioplasty and midface reconstruction, frontal sinus obliteration, soft tissue defect augmentation, laryngoplasty, and ossiculoplasty. The duration of effect of hydroxyapatite implants varies with the use. For cranioplasty the reconstruction is long-lived, with osseoconversion noted; with the injectable form, results are noted to last at least 2 years [30]. Summary The number and variety of soft tissue implants and fillers at the clinician’s disposal continues to increase rapidly as new materials and bioengineering techniques evolve. The ideal implant for all purposes does not yet exist, so the clinician must be familiar with a wide variety of products for each application. Continued advances in synthetic, allogeneic, and autologous products and experience with existing products will further augment the surgeon’s armamentarium in the coming years. References [1] Van Meekren J. Observation medicohisurgicae. Amsterdam: Henrici and T. Bloom; 1670. [2] Terion EO. AlloDerm acellular dermal graft: applications in esthetic and reconstructive soft tissue augmentation. In: Klein AW, editor. Tissue augmentation in clinical practice: procedures and techniques. New York: Dekker; 1998. p. 349–77. [3] Chao C, Freidman C, Alford E, et al. Acellular dermal allograft prevents postparotidectomy soft tissue defects: a preliminary experience. Journal of Otorhinolaryngology Head and Neck 1999;2:1–6.
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[4] Achauer BM, VanderKam VM, Celikoz B, et al. Augmentation of facial soft-tissue defects with AlloDerm dermal graft. Ann Plast Surg 1998;41:503–7. [5] Jackson IT, Yavuzer R. AlloDerm for dorsal nasal irregularities. Plast Reconstr Surg 2001; 107:553–8. [6] Rhee PH, Friedman CD, Ridge JA, et al. The use of processed allograft dermal matrix for intraoral resurfacing: an alternative to split-thickness skin grafts. Arch Otolaryngol Head Neck Surg 1998;124:1201–4. [7] Cohen NA, Mirza N. Acellular human dermal allograft in repair of unilateral partialthickness and full-thickness nasal septal mucosal defects. Laryngoscope 2000;110:2005–8. [8] Winslow CP, Wang TD, Wax MK. Static reanimation of the paralyzed face with an acellular dermal allograft sling. Arch Facial Plast Surg 2001;3:55–7. [9] Niechajev I. Porous polyethylene implants for nasal reconstruction: clinical and histologic studies. Aesthetic Plast Surg 1999;23:395–402. [10] Sabini P, Sclafani AP, Romo T, et al. Modulation of tissue ingrowth into porous highdensity polyethylene implants with basic fibroblast growth factor and autologous blood clot. Arch Facial Plast Surg 2000;2:27–33. [11] Hashem FK, Al Homsi M, Mahasin ZZ, et al. Laryngotracheoplasty using the Medpor implant: an animal model. J Otolaryngol 2001;30:334–9. [12] Ozturk S, Sengezer M, Coskun U, et al. An unusual complication of a Medpor implant in nasal reconstruction: a case report. Aesthetic Plast Surg 2002;26:419–22. [13] You JR, Seo JH, Kim YH, et al. Six cases of bacterial infection in porous orbital implants. Jpn J Ophthalmol 2003;47:512–8. [14] Knapp TR, Kaplan EN, Daniels JR. Injectable collagen for soft tissue augmentation. Plast Reconstr Surg 1977;60:389–405. [15] Framer FM, Churukium MM. Clinical use of injectable collagen: a three-year retrospective review. Arch Otolaryngol 1984;110:93–8. [16] Cooperman LS, Mackinnon V, Bechler G, et al. Injectable collagen: a six-year clinical investigation. Aesthetic Plast Surg 1985;9:145–51. [17] Stegman S, Chu S, Armstrong R. Adverse reactions to bovine collagen implant: clinical and histologic features. J Dermatol Surg Oncol 1988;14(Suppl):39–48. [18] Narins RS, Brandt F, Leyden J, et al. A randomized, double-blind, multicenter comparison of the efficacy and tolerability of restylane versus Zyplast for the correction of nasolabial folds. Dermatol Surg 2003;29:588–95. [19] Watson D, Keller GS, Lacombe V, et al. Autologous fibroblasts for treatment of facial rhytids and dermal depressions. Arch Facial Plast Surg 1999;1:165–70. [20] Boss WK, Usal H, Fodor PB, et al. Autologous cultured fibroblasts: a protein repair system. Ann Plast Surg 2000;44:536–42. [21] Fagien S. Facial soft-tissue augmentation with injectable autologous and allogeneic human tissue collagen matrix (Autologen and Dermalogen). Plast Reconstr Surg 2000; 105:362–73. [22] DeVore DP, Kelman CD, Fagien S, et al. Autologen: autologous, injectable dermal collagen. In: Bosniak S, editor. Principles and practice of ophthalmic plastic and reconstructive surgery. Philadelphia: WB Saunders; 1995. p. 650–75. [23] Sclafani AP, Romo T, Parker A, et al. Autologous collagen dispersion (Autologen) as a dermal filler: clinical observations and histologic findings. Arch Facial Plast Surg 2000; 2:48–52. [24] Sclafani AP, Romo T, Parker A, et al. Homologous collagen dispersion (Dermalogen) as a dermal filler: persistence and histology compared with bovine collagen. Ann Plast Surg 2002;49:181–8. [25] Courey MS. Homologous collagen substances for vocal fold augmentation. Laryngoscope 2001;111:747–58. [26] Moody BR, Sengelmann RD. Self-limited adverse reaction to human-derived collagen injectable product. Dermatol Surg 2000;26:936–8.
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[27] Sclafani AP, Romo T, Jacono AA, et al. Evaluation of acellular dermal graft in sheet (AlloDerm) and injectable (micronized AlloDerm) forms for soft tissue augmentation. Clinical observations and histological analysis. Arch Facial Plast Surg 2000;2:130–6. [28] Pearl AW, Woo P, Ostrowski R, et al. A preliminary report on micronized AlloDerm injection laryngoplasty. Laryngoscope 2002;112:990–6. [29] Friedman CD, Costantino PD, Takagi S, et al. BoneSource hydroxyapatite cement: a novel biomaterial for craniofacial skeletal tissue engineering and reconstruction. J Biomed Mater Res 1998;43:428–32. [30] Tzikas TL. Evaluation of the radiance FN soft tissue filler for facial soft tissue augmentation. Arch Facial Plast Surg 2004;6:234–9.