The Use of Processed Allograft Dermal Matrix for Intraoral Resurfacing: An Alternative to Split-Thickness Skin Grafts

Background  The standard reconstruction of significant mucosal defects in head and neck surgery has been split-thickness skin grafting (STSG).

Objective  To examine the use of a commercially available acellular dermal matrix as an alternative to STSG to reduce the scarring and contracture inherent to meshed split-thickness autografting and avoid the additional donor site morbidity.

Patients and Methods  Twenty-nine patients with full-thickness defects of the oral cavity were included in this retrospective chart review. Candidate patients had their operative procedure performed at a tertiary care center during a 24-month period. Allograft dermal matrix, an acellular tissue-processed biomaterial, was applied to these intraoral defects. The defects were reconstructed with an acellular dermal graft matrix in the same technical fashion as with an autologous skin graft. Patients were evaluated for rate of "take," functional return time to reepithelialization, average surface area of graft, associated pain and discomfort, evidence of restrictive graft contracture, patient diagnosis, and graft location within the oral cavity. Any evidence of incomplete graft reepithelialization was considered grounds for graft failure, either complete or incomplete. Epithelialization and contracture were assessed during outpatient clinical examinations. Patient complaints with regard to discomfort at the graft bed were considered evidence of pain.

Results  Graft locations included 9 in the tongue (32%), 5 in the maxillary oral vestibule (17%), 4 in the mandible (14%), 4 in the floor of mouth (14%), 3 in the hard and/or soft palate (10%), 3 in the tonsil (10%), and 1 in the lip (3%). The overall rate of take was 90% with complete epithelialization noted on clinical evaluation within 4 weeks. Patients were followed up for an average of 8.6 months. The average grafted surface area was 25 cm². Pain or discomfort was noted in 3 patients (12%). One patient (4%) was noted to have clinical evidence of graft contracture.

Conclusions  Allograft dermal matrix was successful as a substitute to autologous STSG for resurfacing of intraoral defects. Allograft dermal matrix may be considered a useful reconstructive option for patients with oral mucosal defects.

NEOPLASTIC, tramatic, and inflammatory diseases of the oral cavity and oropharynx frequently result in significant defects that present reconstructive challenges. Regional and distant flaps restore bulk and preserve function. Split-thickness skin grafts (STSGs) are routinely used to cover the often significant mucosal defects arising from resections.

Conventional STSGs are associated with donor site morbidity, including pain, infection, and hypertrophic scar formation. In addition, full-thickness defects reconstructed with STSGs are associated with significant contracture resulting from a relative lack of dermis. Previous attempts at avoiding these sequelae with the use of allograft donor skin have been limited by their ultimate rejection after a short period of incorporation.¹

In this study, a series of patients underwent mucosal defect reconstruction with a newly developed commercially available acellular dermal matrix processed from human allograft skin. When used intraorally, this processed allograft skin (Alloderm, Lifecell Corporation, The Woodlands, Tex) demonstrated a high percentage of "take," with host cell infiltration and neovascularization, as well as epithelialization from surrounding tissues. There was no evidence of the cell-mediated immune response typically seen with allograft rejection. The acceptance of the allograft matrix (an acellular tissue-processed biomaterial acting as an immunologically inert dermal transplant [Lifecell Corporation]) is thought to result from the low immunogenicity of the acellular dermal components.^2,3

A retrospective review was conducted of patients who underwent operative resection of primary intraoral tumors during a 24-month period between 1996 and 1998 at a tertiary care center. Primary lesion locations included tongue, floor of mouth, maxilla, mandible, hard and/or soft palate, lip, and tonsil. All patients required reconstruction of significant full-thickness intraoral mucosal defects. Patients with a history of preoperative radiotherapy were excluded. The operative approach was multidisciplinary, involving both head and neck and plastic surgeons.

Mucosal defects were reconstructed with the allograft dermal matrix in the same technical fashion as with an autologous skin graft. Grafts were sutured into place using interrupted absorbable sutures, with bolster dressings applied as necessary.

Bolsters were removed following a graft incorporation period and the reconstructed area was examined at frequent intervals, including periodic clinic visits. Patient charts were studied for rate of take, associated pain and discomfort, evidence of graft contracture, average grafted area, mean follow-up time, and graft location within the oral cavity. Any evidence of unsuccessful graft epithelialization or graft sloughing was considered grounds for failure. Pain and discomfort were assessed on clinic visitation and considered significant if the patient experienced symptoms at the graft bed site. Contracture was also assessed on follow-up visits during examination of the grafted region, with attention to restriction of motion or altered function.

Histologic analysis was performed from a specimen obtained from the graft bed of a recipient patient 2 weeks following graft implantation. A representative sample was removed following administration of local anesthesia. The sample was then permanently fixed and examined using light microscopy following staining with hematoxylin-eosin.

Thirty patients were initially selected as study candidates. One patient was excluded due to the use of preoperative radiation. Figure 1 illustrates patient diagnosis at the time of resection and Figure 2 illustrates patient tumor location.

Table 1 demonstrates the outcomes of this study. Our observed rate of take was 90%, with 26 of the 29 patients exhibiting graft incorporation. Epithelialization was noted in all successful grafts within 4 weeks. The average grafted area was 25 cm². At the time of writing, patients had been followed up for an average of 8.6 months following graft placement. Some form of discomfort was experienced by 3 patients (12%). Contracture was noted in 1 patient (4%), which was in the setting of a tumor recurrence.

As can be seen in Figure 3, results of histologic analysis demonstrated graft epithelialization from surrounding tissues as well as host cell infiltration of the allograft dermis.

The optimal method of reconstruction for composite resection defects of the oral cavity is controversial. Larger defects may require microsurgical flap reconstruction while smaller defects may be repaired with STSG alone or allowed to granulate with contracture.⁴ Patients in this study underwent resection of intraoral lesions for a variety of reasons, ranging from dysplastic changes to advanced invasive carcinomas. Until recently, autologous STSG was used for the reconstruction of major mucosal defects. Split-thickness skin grafts were used for both definitive resurfacing and for coverage of muscular flaps.

Scarring and contracture are the major long-term sequelae of STSG for full-thickness defects in the absence of dermis. Scarring and contracture can ultimately result in a loss of function. Previous attempts at avoiding these sequelae with the use of allograft donor dermis have been limited by its immunogenetic properties. The relative availability of autologous skin tissue and the ease with which STSG has been utilized made it the standard of care at most institutions for the reconstruction of head and neck mucosal defects. The recent development of an acellular dermal matrix offers a new treatment option that may prevent the scarring and contracture typical of intraoral STSG and thus help preserve tissue function. As an added benefit, the allograft dermal matrix also avoids the morbidity associated with graft harvesting. Its efficacy in the management of full-thickness burns has been documented.^5-7

The immunogenetic response to allograft skin is directed primarily against the cells composing the epidermis as well as those within the dermis. Until recently, it has not been possible to remove these immunogenetic cells without disrupting the integrity of the remaining components of allograft dermis. Histologic analysis of porcine acellular allograft dermis used to reconstruct full-thickness defects have demonstrated that this matrix supports fibroblast infiltration, neovascularization, and keratinocyte migration from overlying STSG.² Our study suggests an analogous sequence of healing for human intraoral grafts, with the allograft dermis supporting epithelialization by the migration of peripheral cells and matrix-supported cell migration. Both of these processes are demonstrated in histologic analysis of a graft bed following incorporation. These findings are comparable to observed allograft incorporation into burned skin.⁸

Patients in this study had mucosal defects of varying sizes and at different locations within the oral cavity successfully repaired with allograft dermis. As mentioned previously, we excluded patients who had received preoperative radiation to reduce poor graft bed vascularity as a cause for graft failure.

Overall, our success rate is comparable to the 90% success rate quoted for conventional intraoral STSG. Taken together with the allograft matrix's ability to avoid donor site morbidity with low short-term scarring and contracture, these results support its use as a reconstructive option for patients with oral mucosal defects.

Accepted for publication July 16, 1998.

Presented as a poster at the Annual Meeting of the Society of Head and Neck Surgeons, Palm Beach, Fla, May 15-16, 1998.

Corresponding author: Craig D. Friedman, MD, Craniofacial Tissue Engineering, Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia, PA 19111.