Implants, Soft Tissue, AlloDerm
- Author: Michael Mercandetti, MD, MBA, FACS; Chief Editor: Arlen D Meyers, MD, MBA more...
Products
AlloDerm is a soft-tissue implant fabricated by a proprietary method of processing cadaveric skin. This method produces an acellular dermis that is free of the cells responsible for the antigenic response to allograft skin. After processing, the skin is reduced to a basement membrane and properly oriented dermal collagen matrix. The end result is an acellular human dermis that theoretically will not be rejected.
Category
Soft-tissue implants
Device details
Subdermal soft-tissue implants
LifeCell Corporation
- AlloDerm
Injectable, micronized soft-tissue implants
LifeCell Corporation
- Cymetra
Allergan, Inc
- Zyderm
- Zyplast
Collagenesis, Inc
- Autologen
- Dermalogen
Design Features
Tissue banks procure fresh human cadaveric skin following American Association of Tissue Bank (AATB) guidelines. All donor medical history and serologic screening are performed in accordance with the AATB and US Food and Drug Administration (FDA) guidelines. All tissue is tracked from donor to recipient, and related samples are archived.
Benefits of AlloDerm application
AlloDerm can be used in patients of any age; physicians have successfully treated patients aged 2-80 years using this material.
The basic benefits that apply to all AlloDerm applications include the following:
- The tissue is nonreactive, and the graft remodels like autogenous tissue[1]
- No migration occurs, and the graft integrates into surrounding tissue
- After rehydration, AlloDerm is pliable and can be cut, folded, or rolled
- The material is strong and sutures like tissue
- Only 10 minutes of rehydration is required
- The material eliminates donor site trauma
- Volume persistence is maintained during the remodeling period of the integument
Technical considerations
Aseptic processing is then performed by a patented method. The processing of the dermis involves removal of the epidermis under tonic conditions that induce separation of the anchoring fibrils from the hemidesmosomes of the basal keratinocytes. The fibroblasts are then extracted from the dermal matrix under conditions that do not alter the collagen bundles or damage the basement membrane complex. The resulting acellular matrix is then cryoprotected. Cryoprotection elevates the glass transition temperature of the matrix to a level compatible with conventional freeze-drying temperatures. The cryoprotected matrix is then frozen in a lyophilizer and dried with a 2-step drying procedure. See the following image.
Schematic of AlloDerm processing. Matrix integrity is assessed throughout the process by electron microscopy to verify retention of the basement membrane complex, normal collagen bundle, and binding patterns during removal of cellular material (see the image below). All samples are processed with an accompanying satellite sample.
Electron micrographs of allograft skin (left) and AlloDerm (right). The AlloDerm shows intact collagen fiber bundles (CF), elastin (E), and space previously occupied by a dermal fibroblast (arrows). The bars represent 5 micrometers. Following full processing, all satellite samples are reassessed for microbiologic culture. Any bacterial growth is regarded as contamination and results in failure to obtain quality assurance release. One of the steps used in the AlloDerm process has been demonstrated by an independent contract laboratory to inactivate a concentrated suspension of human immunodeficiency virus (HIV). Although it does not ensure viral sterility, it represents an added safeguard.
Subdermal soft-tissue implants
AlloDerm
AlloDerm is supplied to physicians in packages consisting of a sealed foil bag that contains the material in an inner peel pouch. Each package of AlloDerm contains one piece of freeze-dried acellular human dermis. Rehydration instructions, the product insert, and the tissue transplant return record are attached to the bag. The sheet material, shown below, is available in many different sizes.
Rehydrated AlloDerm. Injectable, micronized soft-tissue implants
Cymetra
Cymetra is an FDA-approved micronized tissue matrix (injectable micronized AlloDerm). It has been used clinically for 7 years. The injectable form of AlloDerm, Cymetra, has recently been made available for use. Micronized AlloDerm is created by homogenizing an AlloDerm sheet cut into strips. This homogenizing process is performed at very low temperatures, preserving both the basement membrane and the integrity of the collagen fibers. The product consists of injectable-sized particles of AlloDerm that maintain the ultrastructure of the dermis and that can easily pass through a 26-gauge needle. Injectable AlloDerm obviates the need for incisions and surgical dissection; additionally, the injectable material allows for more precise placement of the implant.
Injection laryngoplasty, also know as injection medialization laryngoplasty, is a technique whereby Cymetra is injected into the vocal cord to medially displace the cord. The injected Cymetra provides structural support and can be used when the function of the recurrent laryngeal nerve is anticipated or if the prognosis of a unilateral vocal cord paralysis is unknown, but within the first 6 months. Calcium hydroxylapatite (RADIESSE Voice, manufactured by Merz Aesthetics) is another agent used for this. Gelfoam (Pharmacia) had also been used but was recalled in November 2000. Historically, other injectable materials were available.
Dynamic improvement continues in the types of materials available for soft tissue augmentation, and many future studies are required to learn more about the long-term characteristics of each.
Zyderm, Zyplast
Processed type I bovine collagen (Zyderm) has been used successfully since the late 1970s. This material attempts to correct dermal deficits with xenograft dermal proteins. Its major drawback is loss of volume persistence over weeks to months. In an attempt to solve this problem, the manufacturer produced Zyplast, which is a type I bovine collagen cross-linked with glutaraldehyde. Zyplast lasts longer than non–cross-linked Zyderm, although both materials are eventually resorbed completely. Allergic reactions have been reported from both products in 3% of patients.
Autologen, Dermalogen
Injectable suspensions that consist predominantly of type I collagen (Autologen, Dermalogen) are also used to fill soft tissue defects. Autologen was composed of autologous collagen extracted from skin procured from the patient during previous elective surgery. Dermalogen is similar, except the skin is obtained from tissue banks and routinely processed. The major drawbacks to Autologen were the requirement of the previous surgical procedure to acquire skin and a processing time of 3-4 weeks; with Dermalogen, the collagen may be damaged during the processing, increasing its antigenicity.
Indications
The following briefly describes some of the many uses of AlloDerm in otolaryngology and head and neck surgery.[2] Listing all the potential uses of this unique material is not possible; however, a basic overview is provided. This information is not designed to be a protocol or specific instructions for the implantation of this material. As always, the physician should exercise individual judgment regarding the possible uses of AlloDerm.
Parotidectomy
Replacing large volumes of isolated soft tissue following oncologic surgical resection remains a challenge to the surgeon. Very few synthetic or semisynthetic materials have been effective for long-term reconstruction. Traditionally, large defects have been filled with autogenous tissue, which must be harvested in either a vascularized or nonvascularized form. This process extends operating time and often results in postoperative morbidity. Synthetic biomaterials, such as expanded polytetrafluoroethylene sheeting, avoid the problems of autogenous grafts, but they are not ideal. The risk of eventual infection or extrusion always is present, even years after implantation.
Implantation of the AlloDerm graft for large-area defect repair is usually accomplished with the patient under general anesthesia. Based on the size of the defect requiring correction, either the 2 × 4-cm or the 3 × 7-cm size of thick AlloDerm graft can be selected. The AlloDerm easily can be rehydrated in 2 washes of sterile isotonic sodium chloride solution for a minimum of 5 minutes per wash. Prophylactic intravenous antibiotic may be administered 30 minutes before incision at the discretion of the surgeon. Several sheets of the AlloDerm graft may then be trimmed and stacked into the defect to replace the inadequate soft tissue.
The sheets may be sutured together to aid placement and prevent shifting during the immediate postoperative period. A slightly larger sheet then may be used to cover the stacked sheets placed in the cavity, thereby providing a single smooth surface underneath the patient's skin to minimize the potential for cutaneous irregularity over the implantation site. The most superficial AlloDerm sheet (which also should be the largest in surface area) can be notched around its perimeter to feather the edge and may facilitate graft integration within the surrounding soft tissue.
Care should also be taken, whenever possible, to secure the edges of this AlloDerm top sheet at multiple points around its perimeter with a 4-0 clear nylon suture. Meticulous hemostasis is important before closure to prevent an excess collection of blood and seroma formation. A small suction drain should be placed into the surgical cavity before wound closure and exited through a separate stab wound. The use of suction drainage is strongly recommended when multiple sheets of AlloDerm are stacked and implanted.
Lip augmentation
A number of case studies concerning the use of AlloDerm in lip augmentation and lip reconstruction have been presented. Several examples presented in the literature use the sheet material and obtain excellent cosmetic results and little loss of volume at follow-up care. A patient undergoing revision surgery after an evulsion injury is an excellent candidate for an AlloDerm reconstruction. After rehydration, the pliability of AlloDerm allows individual shaping of the graft contour to best fit the defect. This allows for excellent customization (eg, having minimal increase in lateral quadrants with increased bulk at midline).
One example of the surgical procedure using the sheet AlloDerm graft for lip augmentation can usually be performed with a local anesthetic block on an outpatient basis. Horizontal stab incisions are made with a number 11 blade at the vermilion border in the lateral commissure of the lip. The plane superficial to the orbicularis oris muscle is identified using blunt scissors for approximately 1-1.5 cm. Blunt dissection along the vermilion border in the submucosal/supra orbicularis oris muscle plane may be performed using a canthal awl, creating a tunnel connecting the lateral stab incisions.
The AlloDerm graft is then rehydrated in sterile isotonic sodium chloride solution, and the resulting soft pliable material may be trimmed to the appropriate dimensions with scissors. Then, the AlloDerm may be rolled upon itself to form a cylinder, and interrupted 4-0 chromic sutures may be used to secure the roll. The graft may then be affixed to the end of a canthal awl and pulled through the previously created submucosal tunnel.
After appropriate positioning, the graft may be sutured in place with 2 interrupted 4-0 chromic sutures placed in the submucosal plane at the commissures. A study demonstrated that the use of AlloDerm in the aforementioned fashion yields a superior result compared with the use of autologous fat.[3]
Nasal septum perforation
A detailed description of the surgical procedure for nasal septal perforation is beyond the scope of this manuscript (see Septal Perforation - Surgical Aspects). Different operative plans are used depending on the size of the defect. Small nasal septal perforations are usually described as those less than 2 cm, whereas large defects are greater than 2 cm.
The surgical technique used for closures of small nasal septal perforations consists of an extended external rhinoplasty approach with elevation, rotation, and meticulous suture closure of the perforation. Bilateral intranasal mucosal flaps with a posteriorly based pedicle are used. AlloDerm material has been used as an interpositional graft between the septal flaps to repair the defect and eliminate the need to obtain an autograft.[4]
After exposure of the septal defect, an AlloDerm graft is secured to the septal cartilage with 5-0 Vicryl sutures superior to the perforation and then allowed to drape over and completely cover the perforation on one side of the septal cartilage. The mucoperichondrial flap is laid into position over the top of the AlloDerm graft. Sutures secure the remaining edges of the graft and flap. This procedure is then repeated on the contralateral side of the nasal septum.
A similar procedure is used to correct large nasal septal perforations using AlloDerm material. The main difference is that this procedure is typically performed in 2 stages, which usually requires tissue expansion to produce flaps large enough to cover the increased area.
Nasal reconstruction
A traumatic nasal deformity can be corrected using a combination of AlloDerm and cartilage. AlloDerm has been used as an onlay graft to restore contour to a saddle deformity, and it has been used in conjunction with the autogenous auricular cartilage to form a premaxillary implant. Dorsal correction and contour have been maintained 1 year after surgery, and no evidence of resorption was present in the areas where AlloDerm was used to replace damaged tissue. Importantly, AlloDerm is used as a scaffold and bulking agent but does not provide structural support.
Rhytid revision
AlloDerm implantation also can help treat premature onset of dermal atrophy leading to inadequate integument and a perioral disfigurement. This particular revision can be accomplished in the office with the patient under local anesthesia. The AlloDerm sheet material may be rolled and implanted in the perioral area using a procedure similar to that described for lip augmentation.[5]
Depressed scar revision
AlloDerm has also been successfully used in procedures to revise depressed scars in the midface area.[6] AlloDerm was used in conjunction with a W-plasty to reconstruct areas of depressed and hypertrophied scars. The scar may be excised along its entire course. When excising the scar, a W-plasty may be performed and the triangular flaps may be interdigitated and closed over the AlloDerm graft. The rehydrated graft may be folded over to create the appropriate size before insertion into the subcutaneous area.
Significantly improved cosmetic result has been noted at 8 and 10 months postoperatively, which indicates that this contour probably is maintained throughout the remodeling period.
Other uses
Other suggested uses for AlloDerm include plastic surgery of the eyelid and orbit, repair of the dura, tympanic membrane reconstruction, reconstruction of the nasal dorsum and tip, wound ulcer treatment, and effacement of nasal labial folds.
Clinical Trial Evidence
A large body of literature demonstrates the utility of AlloDerm for the treatment of full-thickness burns. This topic is beyond the scope of this manuscript; however, the reader is referred to excellent journal articles written on the subject.[7, 8, 9] Moreover, authors such as Schulmann provide significant documentation about the use of AlloDerm in the gingiva.[10]
Lip augmentation
A number of case studies concerning the use of AlloDerm in lip augmentation and lip reconstruction have been presented. Several examples presented in the literature use the sheet material and obtain excellent cosmetic results and little loss of volume at follow-up care.
A study demonstrated that the use of AlloDerm in lip augmentation yields a superior result compared with the use of autologous fat.[3]
Nasal reconstruction
Dorsal correction and contour have been maintained 1 year after surgery, and no evidence of resorption was present in the areas where AlloDerm was used to replace damaged tissue.
Depressed scar revision
Significantly improved cosmetic result has been noted at 8 and 10 months postoperatively, which indicates that this contour probably is maintained throughout the remodeling period.[6]
Clinical Implementation
Throughout history, multiple approaches have been used to replace lost, damaged, or diseased tissues. Some methods use synthetics, biosynthetic constructs, cross-linked biologic materials, or preserved allografts. Investigations using these approaches have supplied increasing evidence that the matrix component of tissue replacement must be complex.
The physician must understand the normal structure of the integument and how this arrangement is either preserved or slightly altered by the fabrication methods of these allograft materials. These concepts become increasingly important when considering the remodeling of the allograft material after implantation into the patient. Factors to be considered by the physician while selecting the allograft material include the patient's medical history, the anatomic site of implantation, the desired result, and the chosen material type.
Integument structure
Skin consists of 2 essential layers: (1) the epidermis, which provides a barrier against the environment, and (2) the dermis, which provides strength, durability, and elasticity. The dermis of the skin is a complex multicomponent matrix. In contrast to skin of other species, human skin lacks a panniculus, or underlying muscle sheath. Because many allograft materials are xenografts, this anatomic fact is important to remember. Consequently, the human dermis has evolved as a multilayered complex organ able to deal with the stress patterns resulting from the relative immobility of human skin. The layers of the dermis include the papillary dermis and the reticular dermis. The reticular dermis transitions into the deep reticular-subcutaneous junction.
The important components of the dermis that contribute to its function include the basement membrane complex at the dermal-epidermal junction, collagen, elastin, proteoglycans, and a distinctive vascular plexus. The basement membrane complex at the dermal-epidermal junction contains type IV collagen, laminin, and highly specialized type VII collagen. Type VII collagen forms anchoring fibrils and filaments, which ensure strong physical bonding of the epidermis to the dermis.
The bundle orientation of collagen and elastin differs between the papillary dermis and the reticular dermis. Collagen bundle orientation is random in the papillary dermis, but it is perpendicular to the lines of tension in the deeper reticular dermis. Similarly, elastin fibers are sparse and finely reticular in the papillary dermis, whereas they are thicker and form a complex 3-dimensional (3-D) array in the reticular dermis.
The dermal vasculature forms a distinct plexus in the papillary dermis. This plexus configuration plays an important role in the remodeling process, because collagen deposition tends to occur along the pathways of neovascularization. If the plexus is absent, collagen remodeling occurs along the pathways of an altered vascular pattern, as evident in granulation tissue in scar formation. Proteoglycans of the dermis provide a reservoir for growth factors (eg, basic fibroblast growth factor [FGF] binds to heparin sulfate). Dermal proteoglycans also direct the assembly of collagen (eg, decorin, tenascin) or are involved directly in angiogenesis and the regulation of cellular functions (eg, hyaluronic acid, chondroitin sulfate). Each of these factors plays a significant role in the ability of the allograft material to maintain volume persistence over time.
Dermal function depends on the intricate and complex organization of the extracellular matrix components and their interactions. Matrix components include collagen fibrils oriented perpendicular to the lines of stress, an elastin network consisting of elastin and microfibrillar fibers, diverse and compartmentalized proteoglycan species, and a structurally unique basement membrane complex.
Wound healing
Following full-thickness skin injury, the epidermis heals rapidly by regeneration. However, the dermis is not capable of regeneration and, therefore, heals by repair. This repair process begins with the formation of granulation tissue, which subsequently matures into the scar tissue. This process often leads to disfigurement and functional impairment of the integument. Scar tissue is different from the dermis, because it is a relatively simple, undifferentiated structure consisting of parallel arrays of collagen bundles that orient parallel to the lines of stress. Scar tissue also lacks elastin, normal distribution of proteoglycans, and the organs of the normal dermis.
Because of the limited supply of human donor tissue, an ideal approach to replacing lost dermis is to use a synthetic or biosynthetic material. Allograft skin and cross-linked porcine skin have been used as temporary wound dressings, but they cannot provide a permanent dermal replacement, because they are either rejected or do not revascularize.
Allograft rejection
The cause of allograft rejection is a subject of continued research and controversy. The use of allograft donor skin as a permanent skin replacement in full-thickness injuries is limited by its immunogenic properties.[11, 12] Allograft skin grafts routinely incorporate to a full-thickness wound, but they ultimately are rejected. This immune response to allograft skin is directed primarily against the cells of the epidermis and endothelial and fibroblast cells of the dermis.[13] The noncellular components of the dermis, consisting primarily of extracellular matrix proteins and collagen, have been demonstrated to be relatively nonimmunogenic. Before the existence of AlloDerm, the difficulty involved in removing the immunogenic cells from the nonimmunogenic dermis of allograft skin restricted its use to temporary coverage of full-thickness burns.
The concept of permanent transplantation of nonimmunogenic extracellular tissue matrix has been illustrated clearly with the more robust matrix of bone. According to Kreuz et al, freeze-dried bone allografts have been used successfully in permanent bone implants for many years.[14] The cells in these allografts are destroyed during the freeze-drying process, but the structural organization of the extracellular matrix remains intact. These bone allografts do not elicit a specific immune response, and they provide an environment of osteogenic cell repopulation and osteoinduction with subsequent matrix remodeling of a new bone formation. The success of this product illustrates the advantage of supplying a matrix that is remodeled later into normal tissue (see the image below).
A human biopsy sample 15 days postsurgery. Comparison of the control site (left) and the AlloDerm site (right) reveals minimal histologic differences. Analysis of the AlloDerm site reveals infiltration of host fibroblasts and evidence of neovascularization. Complications
Injectable, micronized soft-tissue implants
Zyderm, Zyplast
Allergic reactions have been reported from both products in 3% of patients.
AlloDerm is contraindicated for use in any patient who is sensitive to any of the antibiotics listed on the package or polysorbate 20.
The most worrisome complication would be infection due to contamination of the AlloDerm. Aseptic technique is crucial in the handling of this graft material from its removal via sterile technique, its rehydration, and implantation.
Graft failure is also another issue and may occur as a result of poor recipient interfacing with the graft, such as an infected donor site or a vascularly compromised donor site, or improperly suturing and dressing of the graft.
Sclafani AP, Romo T 3rd, 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. Apr-Jun 2000;2(2):130-6. [Medline].
Jones FR, Schwartz BM, Silverstien P. Use of a non-immunogenic acellular dermal graft for soft tissue augmentation: a preliminary report. Aesthetic Surg J. 1996;16:196-201.
Castor SA, To WC, Papay FA. Lip augmentation with AlloDerm acellular allogenic dermal graft and fat autograft: A comparison with autologous fat injection alone. Aesthetic Plast Surg. May-Jun 1999;23(3):218-23. [Medline].
Kridel RW, Foda H, Lunde KC. Septal perforation repair with acellular human dermal allograft. Arch Otolaryngol Head Neck Surg. Jan 1998;124(1):73-8. [Medline].
Schwartz BM. Rhytid Revision: LifeCell Clinical Case Summary. Houston, TX: LifeCell; 1997.
Silverstein P. Depressed Scar Revision: LifeCell Clinical Case Summary. Houston, TX: LifeCell; 1997.
Rigal C, Pieraggi MT, Serre G, et al. Optimization of a model of full-thickness epidermal burns in the pig and immunohistochemical study of epidermodermal junction regeneration during burn healing. Dermatology. 1992;184(2):103-10. [Medline].
Sheridan R, Choucair R, Donelan M, et al. Acellular allodermis in burns surgery: 1-year results of a pilot trial. J Burn Care Rehabil. Nov-Dec 1998;19(6):528-30. [Medline].
Wainwright DJ. Use of an acellular allograft dermal matrix (AlloDerm) in the management of full-thickness burns. Burns. Jun 1995;21(4):243-8. [Medline].
Schulmann DM. The acellular dermal matrix: soft-tissue development for dental implants. Dent Implantol Update. Sep 2001;12(9):65-71. [Medline].
Griffey S, Schwade ND, Wright CG. Particulate dermal matrix as an injectable soft tissue replacement material. J Biomed Mater Res. 2001;58(1):10-5. [Medline].
Rigal C, Pieraggi MT, Vincent C, et al. Healing of full-thickness cutaneous wounds in the pig. I. Immunohistochemical study of epidermo-dermal junction regeneration. J Invest Dermatol. May 1991;96(5):777-85. [Medline].
Gryskiewicz JM. Dorsal Augmentation with AlloDerm. Semin Plast Surg. May 2008;22 (2):90-103. [Medline].
Sedmak DD, Orosz CG. The role of vascular endothelial cells in transplantation. Arch Pathol Lab Med. Mar 1991;115(3):260-5. [Medline].
Cohen MS, Mehta DK, Maguire RC, Simons JP. Injection medialization laryngoplasty in children. Arch Otolaryngol Head Neck Surg. Mar 2011;137 (3):264-268. [Medline].
Hwang K, Hwang JH, Park JH, Kim DJ, Shin YH. Experimental study of autologous cartilage, acellular cadaveric dermis, lyophilized bovine pericardium, and irradiated bovine tendon: applicability tonasal tip plasty. J Craniofac Surg. May 2007;18 (3):551-558. [Medline].
Kreuz FP, Hyatt GW, Turner TC, Bassett AL. The preservation and clinical use of freeze-dried bone. J Bone Joint Surg Am. Oct 1951;33-A(4):863-72; passim. [Medline].
Lamke LO. The influence of different "skin grafts" on the evaporative water loss from burns. Scand J Plast Reconstr Surg. 1971;5(2):82-6. [Medline].
Lavker RM, Dong G, Zheng PS, Murphy GF. Hairless micropig skin. A novel model for studies of cutaneous biology. Am J Pathol. Mar 1991;138(3):687-97. [Medline]. [Full Text].
Levy D, Banta M, Charles C, Eaglstein WH, Kirsner RS. Cymetra: A Treatment Option for Refractory Ulcers. Wounds [serial online]. 16 (12) 2004:359-363. Available at http://www.medscape.com/viewarticle/497391.
Maloney BP. Cosmetic surgery of the lips. Facial Plast Surg. Jul 1996;12(3):265-78. [Medline].
Milstein CF, Akst LM, Hicks MD, Abelson TI, Strome M. Long-term effects of micronized AlloDerm injection for unilateral vocal fold paralysi. Laryngoscope. Sep 2005;115 (9):1691-1696.
Papel ID, Mabrie DC. Deprojecting the nasal profile. Otolaryngol Clin North Am. Feb 1999;32(1):65-87. [Medline].
Pearl AW, Woo P, Ostrowski R, Mojica J, Mandell DL, Costantino P. A preliminary report on micronized AlloDerm injection laryngoplasty. Larynoscope. June 2002;112(6):990-996. [Medline].
Romo T 3rd, Sclafani AP, Falk AN, Toffel PH. A graduated approach to the repair of nasal septal perforations. Plast Reconstr Surg. Jan 1999;103(1):66-75. [Medline].
Rosen CA, Gartner-Schmidt J, Casiano R, Anderson TD, Johnson F, Remacle M, et al. Vocal fold augmentation with calcium hydroxylapatite: twelve-month report. Laryngoscope. May 2009;119 (5):1033-1041. [Medline].
Tan M, Woo P. Injection laryngoplasty with micronized dermis: a 10-year experience with 381injections in 344 patients. Laryngoscope. Dec 2010;120 (12):2460-2466. [Medline].
Print
