Use of Collagen-glycosaminoglycan Silicone Bilayer Matrix for Closure of Post-Mohs Micrographic Surgery Defects on the Nose: A 5-case Series

There are over 5 million cases of skin cancers reported in the United States annually.¹ MMS has proven its utility and accuracy for resecting cutaneous tumors.² A retrospective analysis of the National Ambulatory Medical Care Survey for patient visits associated with MMS from 1995 to 2010 showed a low percentage (mean, 10.0%) with an upward trend of skin cancers managed with this technique.³ MMS was most commonly used for the head and neck region. Demographic groups receiving MMS at higher rates included African Americans (44.2%) and patients aged 75 to 84 years (12.4%).³ Most of the defects created by cancer resection require some form of surgical repair. Several types of reconstructions can be used following MMS: linear repair, flaps, skin grafts, and secondary intention.⁴ The choice of the reconstruction will depend on the type, location, and size of the defect; the patient’s profile; and the surgeon’s skills and preferences.⁵ In a retrospective analyses of 975 medical records of patients undergoing MMS for skin cancer, linear closure was the most common repair (39%) in most histological subtypes and anatomical locations studied.⁶ In clinical centers where an MMS service is available, reconstruction may be done immediately after resection because tumor clearance is provided instantly with on-the-table analysis during the procedure.^7-9

Nose surgical wounds can be challenging, even for most experienced dermatological surgeons. Obtaining consistent and cosmetically satisfactory results for nasal reconstruction following resection of nasal carcinomas is more complex than anticipated. This is due to the paucity of available skin for remodeling, the difficulty of obtaining an acceptable skin match through autograft, the complex shape and anatomical function of the nose, and the effect of the nose on the overall appearance of the face. Dr. Frederick Menick, a highly regarded specialist in nasal reconstruction who pioneered the use of vascular lining combined with delayed primary cartilage grafts in full-thickness defects of the nose, has reported and reviewed clinical cases of increasing composite complexity over the years.^10,11 However, for the majority of plastic surgeons and dermatologists who face large volumes of reconstructive cases of less invasive defects, the options are full-thickness skin grafts, local flaps and healing by secondary intention.^12-16 Reconstruction in this setting has been inconsistent in achieving a cosmetic and aesthetically acceptable nasal defect reconstruction.^17,18

MMS is particularly suited for resecting cutaneous tumors of the eyes, ears, nose, and lips because it minimizes the size of the wound and consequent distortions at these critical sites.¹⁹ Following MMS, tumor location can influence the closure type choice. In a 2020 study by Brandão et al, nose defects presented at 39% higher frequency of other closure types, such as flap modalities rather than linear repairs, when compared with defects in other anatomic sites after MMS.⁶ These options are not always feasible because of limitations in donor tissues, defect shape or size, oncologic issues, or patient preference. The population requiring repair of the nose following cancer resection is commonly in the fourth through eighth decade of life, with many having multiple chronic health issues that contribute to healing difficulties. This population seeks a simple, minimally invasive, 1-stage procedure with cosmetically satisfactory results.

Integra Bilayer Wound Matrix (BWM; Integra LifeSciences, Princeton, NJ) is a bioengineered xenogenic bilayer dermal matrix composed of a layer of cross-linked type I bovine collagen derived from adult Achilles tendon, glycosaminoglycans (chondroitin-6-sulfate) derived from shark cartilage, and a silicone layer.^20,21 BWM is applied to the wound in a 2-stage procedure.²² First, the dermal matrix is placed over the excised and debrided wound. Second, after 3 to 4 weeks, when neovascularization is achieved and the neodermis is being formed, the silicone layer is removed and replaced by a split-thickness skin graft.²³ Two-stage procedures are generally conducted on patients with large defects who would benefit from a secondary skin graft. If possible, single-stage procedures through epithelialization offer the opportunity to avoid multiple operations and reduce donor-site morbidity.^24,25 Over the years, BWM has been used to manage a broad range of partial and full-thickness wounds from combat casualty injuries, dog-bite injuries, traumatic degloving injuries, donor site coverage, tendon coverage, slow-to-heal wounds, and cancer resection, particularly after MMS.^26-40

At one time, skin grafts, flaps, and healing by secondary intention may have been considered the only options for reconstruction of dermatologic malignancies, but the use of dermal matrices, particularly BWM, has been shown to be a reliable and less-invasive alternative.^41-46 Current literature regarding the use of this technique for reconstructing the nose is scarce, particularly after MMS.⁴⁷ This case series reports the outcomes in 5 adult patients whose wounds were managed using BWM for reconstruction on the nose after MMS. Reconstruction using BWM enables a single-stage process and epithelialization (after removal of the silicone layer) of the nose, which has resulted in satisfactory cosmetic outcomes.

The study was conducted following the principles outlined in the Declaration of Helsinki. All patients were informed of the pros and cons of the use of BWM for the management of their wounds and signed a consent approving or rejecting such information. All patients gave informed written consent for the use of the data collected, including the publication of photographs. Patient selection for this procedure was determined by providing the product at no cost or at low cost if the patient had the means to pay a reduced fee; the aim was to provide the patient with a cosmetic result similar to that of a skin graft, regardless of morbidity.

All procedures were performed in the clinic under local anesthesia on an outpatient basis. The lesions were excised using MMS technique. Following resection and confirmation of negative margins, BWM was placed over the wounds. The sheet of dermal matrix was fixed in place using 4-0 nonabsorbable monofilament polypropylene stitches (for ease of use) with simple interrupted sutures. A bolster, consisting of folded Adaptic nonadherent gauze (3M; St. Paul, MN), was applied over the silicone and secured with silk sutures (which were minimally reactive for the short time they were used). The bolster remained in place for up to 2 weeks, or until the silicone layer detached. The incorporation of the dermal matrix to the wound bed was assessed regularly; when the color of the dermal matrix had progressed from pink through pale yellow and finally to peach, a well-vascularized neodermis was revealed.²³ Once the silicone was removed, a hydrocolloid dressing was applied to cover the wound and changed every 3 days.

Case 1

A 71-year-old male was treated at the clinic for a BCC of the left nasal lateral sidewall. The patient was a heavy smoker with no other comorbidities. Due to smoking history, he was a poor candidate for a pedicle or rotation flap. He underwent MMS on the nose, requiring 4 stages of excisions before being cleared. Removal of the tumor was complicated due to the poorly defined clinical tumor borders, large size, and clinical area critical for tissue conservation. The resulting post-MMS defect measured 2.8 cm × 2.2 cm (Figure 1A). The patient was seen at the next available appointment the following day for closure and placement of the BWM over the wound (Figure 1B). Vascularization of the dermal matrix was achieved 13 days after placement, at which time the silicone layer had detached spontaneously and was removed (Figure 1C). Dermal matrix incorporation to the wound bed was 100%. The wound was subsequently allowed to epithelialize. Time for complete healing occurred 11 weeks after dermal matrix placement (Figure 1D). The patient did not adhere to medical advice and continued to smoke; however, no infections or postoperative complications were noted. Despite his poor adherence to medical advice and advanced age which possibly impacted the cosmetic outcome, the wound healed. The patient was satisfied with the final appearance despite contour irregularities and alar rim notching; he did not desire additional scar revision.

Case 2

A 47-year-old male was treated at the clinic for a BCC of the right nasal ala. He had a history of hypertension and was a former smoker. On further evaluation, the patient’s tumor demonstrated aggressive infiltrative histology. Removal of the tumor was complicated by poorly defined clinical tumor borders, large size, clinical area critical for tissue conservation, and tumor occurring in a location of prior radiation. The patient underwent MMS on the nose with 2 stages of excisions before being cleared. The final defect size measured 2.5 cm × 1.5 cm; the wound extended through the lower lateral cartilage (Figure 2A). Placement of the BWM took place 12 days after MMS (Figure 2B). Placement of BWM was delayed while staff obtained authorization from the patient’s insurance for the application of the dermal matrix. During this time, granulation tissue partially filled the wound and the BWM was applied over the granulation tissue. Vascularization of the dermal matrix was achieved 3 weeks after placement, at which time the silicone layer detached spontaneously and was removed (Figure 2C). Dermal matrix incorporation to the wound bed was 100%. The wound was subsequently allowed to epithelialize and was fully healed 4 weeks after the BWM placement; there was noted to be a small area of thickened scar at the anterior edge of the healed wound (Figure 2D). The patient adhered to medical advice, and no infections or postoperative complications were noted. The patient reported complete satisfaction with contour, texture, and cosmetic outcome.

Case 3

A 78-year-old female with a history of hypertension was treated at the clinic for a BCC to the nasal dorsum. She underwent MMS on the nose. Removal of the patient’s tumor was complicated by poorly defined clinical tumor borders and clinical area critical for tissue conservation. She underwent 3 stages of excisions before being cleared. The final defect size measured 2.0 cm × 1.7 cm (Figure 3A). The procedure was delayed to verify the patient’s insurance coverage, and the placement of BWM was performed 6 days after MMS (Figure 3B). Vascularization of the dermal matrix was achieved 3 weeks after placement, at which time the silicone layer detached spontaneously and was removed. Dermal matrix incorporation to the wound bed was 100%. The wound was subsequently allowed to epithelialize. Time to healing occurred 4 weeks after dermal matrix placement (Figure 3C and 3D). The patient adhered to medical advice, and no infections or postoperative complications were noted. Although there were some early contour irregularities to the epithelialized result, these irregularities became less noticeable after the passage of time. The patient reported complete satisfaction with the clinical outcome.

Case 4

A 50-year-old male was treated at the clinic for a BCC to the left medial canthus of the nose. The patient had a history of hypertension and was a former smoker. He underwent MMS on the nose, which required 3 stages of excisions before being cleared. Removal of the patient’s tumor was complicated by poorly defined clinical tumor borders and clinical area critical for tissue conservation. The final defect measured 2.0 cm × 1.5 cm (Figure 4A). The procedure to cover the wound was delayed while staff obtained authorization from the patient’s insurance, and the placement of BWM was performed 2 weeks after MMS (Figure 4B). Vascularization of the dermal matrix was achieved 3 weeks after placement, at which time the silicone layer detached spontaneously and was removed (Figure 4C). Dermal matrix incorporation to the wound bed was 100%. The wound was subsequently allowed to epithelialize. Time to healing occurred 5 weeks after dermal matrix placement (Figure 4D). The patient adhered to medical advice, and no infections or postoperative complications were noted. The patient approved the final result despite hypertrophic scarring and epicanthal fold, which was treated with triamcinolone injection; no further surgery was undertaken.

Case 5

A 73-year-old male was treated at the clinic for a BCC to the left alar lobule of the nose. The patient had a history of hypertension and gastroesophageal reflux disease. He underwent MMS on the nose, which required 4 stages of excisions before being cleared. Removal of the patient’s tumor was complicated by the depth of the tumor. The final defect measured 1.8 cm × 0.8 cm × 0.3 cm (depth to adipose tissue to cartilage; Figure 5A). On the day of MMS, 3 stacked layers of BWM were placed over the wound bed; the silicone layers were removed from the BWM before stacking except for the superficial layer (Figure 5B). Vascularization of the dermal matrices was achieved 7 days after placement, at which time the silicone layer detached spontaneously (Figure 5C). Dermal matrix incorporation to the wound bed was 100%. The wound was subsequently allowed to epithelialize. Time to healing occurred 4 weeks after placement of the dermal matrix (Figure 5D). The patient adhered to medical advice, and no infections or postoperative complications were noted. The patient reported complete satisfaction with the results.

The authors undertook a clinical evaluation to explore the outcome of single-stage reconstruction, through epithelialization, following use of BWM in patients after MMS on the nose. Five patients (1 female and four male; age range, 47-78 years; Table 1) with significant nasal defects following MMS were treated in an outpatient setting. Pathologic evaluation revealed 5 BCCs. None of the patients had a defect extending into the nasal cavity. In all cases, the dermal matrices integrated fully into the wound bed, and complete healing occurred within 11 weeks after matrix placement without a need for additional grafting. For these 5 patients, the incorporation of the dermal matrix to the wound bed was not affected by the patients’ profiles (eg, age, sex, comorbidities, and wound characteristics). Of note, this case series included patients with limited comorbidities (Table 1) and in patient 2, the tumor occurred in a location of prior radiation. There were no complications, such as hematoma, seroma, infection, or bleeding. The reconstructions remained stable, and the patients were satisfied with the cosmetic outcomes. In all 5 cases, full-thickness skin grafting was not performed given the patients’ satisfaction with their postoperative course and results, avoiding potential revision surgeries.

BWM was chosen as an initial stage in these patients because this population of patients seeks a simple, minimally invasive, 1-stage procedure through epithelialization that offers cosmetically satisfactory results. While at one time flaps, skin grafts, and healing by secondary intention may have been considered the only options for reconstruction of dermatologic malignancies after MMS, the use of BWM has shown to be a reliable and less-morbid alternative. These results show the anatomical location of the defects favored using BWM post-MMS in a single-stage procedure and epithelialization. Additionally, many of the patients receive anticoagulant therapy; a single surgical site with minimal invasion leads to lower risk of anti-coagulation complications.

The clinical features of the final healed tissue suggested that the single procedural use of BWM allowed the efficient formation of a neodermis and an effective epithelialization, after removal of the silicone layer. The routine way to use BWM is a 2-stage process.^22,23 Other studies, however, have reported the use of BWM in a single-stage process through healing by epithelialization or in conjunction with skin grafting.^25,25,48 In this case series, the delayed thin/ultra-thin skin autograft procedure was not necessary due to the small defect sizes.As a result, the silicone layer was left to detach spontaneously, which occurred between 7 days and 3 weeks after dermal matrix placement. The wounds were left to heal by epithelialization; time to healing ranged from 4 to 11 weeks after dermal matrix placement for defects ranging from 1.44 cm² to 6.16 cm² (from 1.8 cm × 0.8 cm to 2.8 cm × 2.2 cm; Table 2). The use of BWM in a single-stage process through epithelialization, after silicone layer removal, led to satisfactory cosmetic results.

Stacking dermal matrices is a means to obtain enough volume for reconstruction.⁴⁹ The stacking of BWMs serially has been reported to address defects over the palm of the hand in terms of depth, leading to excellent wound healing, coverage, and full range of motion.⁵⁰ In Patient 5 (wound defect 1.8 cm × 0.8 cm × 0.3 cm), due to the desire to provide additional soft tissue bulk, sheets of BWM were stacked concomitantly over the wound. Utilization of the BWM, either standalone or with stacking, has appeared to allow for healing in a rapid fashion, particularly for larger defects. Patients uniformly were pleased when offered an alternative to harvesting skin from a donor site.

In patients 1, 2, 3, and 4, the dermal matrix was applied on a different day of the MMS procedure: the following day, 12 days after surgery, 6 days after surgery, and 2 weeks after surgery, respectively. In patient 5, BWM was applied to the excised wound on the day of the MMS procedure (Table 2). The reasons for the delays between the MMS procedure and the placement of the dermal matrix were specific to the patient population studied. In these cases, reconstruction was delayed for some patients due to limited appointment availability or to obtain authorization from the patient’s insurance for the dermal matrix. In patients who have undergone MMS, reconstruction may be done immediately after resection as tumor clearance is provided instantly.^7-9 Hence, the probable optimal timing of placement of BWM in patients whose cutaneous tumor is managed with MMS is to apply the dermal matrix to the excised wound immediately after resection once tumor clearance is confirmed.

The outcomes in this case series show that using BWM in a single-stage procedure through epithelialization on the nose post-MMS offers several advantages over skin grafting. BWM appears to minimize any contour deformity that might otherwise result from using a skin autograft to reconstruct the wound, and there is no donor site morbidity. Skin grafts to the nose have variable outcomes in terms of graft take and appearance. In all patients, the authors observed less notable color differences between the healed and surrounding tissues than a skin graft, which often presents a different skin color. Furthermore, BWM can be applied with the patient under local anesthesia and the need for multiple procedures can be avoided; see also Seth et al (2019).⁴⁷ The anatomical location of the defect also favors the use of BWM in single-stage procedure through epithelialization, due to the complex shape and anatomical function of the nose and the effect of the nose on the overall appearance of the face.

The data from this case series support the use of BWM for the management of nose defects post-MMS, whereas the data on dermal matrices and cellular and tissue-based products for managing MMS wounds remain limited and their usage is not well guided.^{42,44,45,47,51} Additional research is needed and should include conducting an ad hoc prospective study. Future directions will involve stem cell-based therapies or growth factors in combination with the BWM to augment skin repair.

There are limitations to using BWM in a single-stage procedure through epithelialization in patients who have undergone MMS. The patients in this case series had wounds that were left to heal by epithelialization and required frequent dressing changes, which is a prolonged process that was acceptable to and well tolerated by the patients. This tolerance may relate to patients’ preference and compliance to avoid additional surgery if a satisfactory cosmetic result could be achieved by using BWM.²⁵

Another limitation of using BWM is its associated financial costs. These costs must be balanced against the costs of an autologous reconstruction and patient outcomes. In these instances, BWM was applied in an outpatient setting, which also saved operating room time and anesthesia costs. Likely, these financial savings offset the material cost. In addition, the use of BWM has an initial steep learning curve for surgeons. The material is also not without risk of complications, such as infection, hematoma and seroma formation, and premature separation of the silicone layer.^52,53

Nasal defects are singularly difficult to reconstruct due to a paucity of available tissues for local reconstruction.  In an aging population with multiple comorbidities, simple is always better. This case series reported on outcomes of 5 adult patients whose wounds were managed using BWM for reconstruction of the nose post-MMS. This strategy enabled a single-stage procedure in an outpatient setting and stable reconstruction that resulted in satisfactory cosmetic outcomes without further autografting needed for closure. More immediate postoperative care was needed, but the long-term cosmetic results were uniformly satisfactory. This brief experience using BWM suggests this material may be an excellent medium for addressing these issues.