Dehydrated Human Amnion/Chorion Membrane Allograft for Postoperative Wounds Following Mohs Micrographic Surgery: A Retrospective Comparative Evaluation

MMS is a surgical technique that has transformed the management of dermatologic neoplasms.¹ This procedure involves the removal of the target lesion and assessment of the margins to ensure that all cancerous cells are removed,² and it preserves the largest amount of healthy tissue and provides the highest cure rate.³ MMS is especially well suited for tumors located at sensitive anatomic sites such as the nose, ears, scalp, and chest; even so, tumors at such sites can pose significant challenges for the Mohs surgeon.⁴ Tissue preservation is particularly important to maximize functional and aesthetic outcomes; however, obtaining clear surgical margins, especially at high tension and in inelastic areas, can result in significant post-excisional defects that can be difficult to suture.⁵ In such cases, secondary intention healing is sometimes preferred, but alternative solutions might be even better suited. 

One potential method to preserve the anatomy and reduce the need for meticulous wound care is the use of dHACM allograft (EpiFix; MiMedx Group, Inc), a cellular- and/or tissue-based product that stimulates endogenous wound healing pathways.^6,7 In several randomized, multicenter clinical trials, dHACM allografts were found to have superior effectiveness in enhancing the healing process and reducing the mean healing time compared with standard wound care alone.⁸ Most studies examined dHACM allografts primarily in the management of chronic diabetic and venous ulcers of the lower extremity.^7,9 There is a paucity of literature on the use of dHACM allograft in post-MMS defects.¹⁰

This pilot study aimed to evaluate the efficacy of dHACM allografts for wound closure following MMS compared with secondary intention healing. The authors hypothesized that postoperative outcomes with dHACM allografts would have a statistically significant advantage over secondary intention healing alone and would reduce the mean time of healing.

This retrospective, case-control study included 310 male and female patients with a diagnosis of either basal cell carcinoma or squamous cell carcinoma who presented to the clinic from 2018 through 2023 for elective MMS. EHRs were searched and relevant information analyzed.

All patients who underwent MMS and completed all recommended follow-up appointments were considered eligible for inclusion. Patients with incomplete data, those who received additional management after primary treatment (eg, sutures), and those using medications that could delay the healing process (eg, corticosteroids, cytotoxic antineoplastic drugs, immunosuppressive agents, anticoagulants) were excluded. Similarly, patients with an active acute skin infection or dermatologic conditions with a skin barrier defect (eg, atopic dermatitis, ichthyosis, irritant contact dermatitis, allergic contact dermatitis, generalized erythroderma) were also excluded because these conditions hinder the normal wound healing process.

Upon evaluation of EHR, wounds were identified based on location, size, and depth, and photographs were analyzed. Wound depth was rated by the Mohs surgeon (N.E.) on a modified scale created by the dermatology research fellows (S.M., A.O.). The scale was inspired by the Bates-Jensen Wound Assessment Tool (grade 1, no break in skin surface; grade 2, superficial, or shallow crater; grade 3, deep crater, or visualization of tissue layers; grade 4, visualization of supporting structures).¹¹ All wounds in the present study were grade 2 or 3.

Based on the eligibility criteria, 40 patients were selected to constitute the cases (dHACM allograft) and 40 patients were selected as control subjects (secondary intention healing). To begin, the selected control subjects were matched based on the size and site of post-MMS defects, after which subjects were matched based on depth (Figure 1).

Patients in the dHACM allograft cohort received up to 5 applications every 2 weeks, in addition to nonadherent dressings and standard wound care. An appropriately sized graft was selected to match the size of the defect, hydrated with 0.9% saline, and placed in the wound bed (Figure 2). In the control group, the wound was left to heal by secondary intention and was hydrated with a medicated ointment with panthenol and glycerin to minimize scarring. Patients in both cohorts were instructed to cover the wound with the same pressure dressing consisting of gauze and surgical tape, and to wash the area with fragrance-free soap and water once daily. Subjects in both cohorts were followed every 2 weeks for wound assessment and cleaning, and for taking photographs. Debridement was performed as necessary for any unhealed cases. Only 2 patients from each cohort required this intervention every other week, and there were no notable differences in pain and hemostasis between treatment groups.

The dermatologic surgeon (N.E.) and 2 dermatology research fellows (S.M., A.O.) graded aesthetic outcomes based on the photographs. Cosmesis was scored on a 2-point scale (1 = “excellent-to-good” meaning no scar, or a fine-line scar; 2 = “fair-to-poor” meaning hypertrophic, keloid, or contracture scar). 

Data were analyzed using the open-source SciPy software (version 1.10.1). Descriptive statistics were demonstrated as mean ± SD. Statistical differences were compared using a 1-sided Wilcoxon rank sum test. Results were considered statistically significant at P < .05.

Of the 310 patients who presented for elective MMS, 80 met the criteria for inclusion in the final analysis. A total of 40 patients (22 male, 18 female) were treated with dHACM allograft, and 40 patients (25 male, 15 female) constituted the control group. The mean age at treatment was 61.4 years in the treatment group and 63.2 years in the control group. The average time to complete healing was 5.2 weeks ± 2.4 in the dHACM allograft cohort and 6.5 weeks ± 2.7 in the control group (Table). Healing time was 80% faster following the application of dHACM than in similar wounds treated by secondary intention.

The Wilcoxon rank sum test was associated with a statistically significant effect (P = .01). Thus, the use of dHACM allografts for post-MMS defects was associated with a statistically significant reduction in time to complete healing compared with secondary intention healing. Additionally, there was no noticeable difference in cosmesis between groups based on the 2-point scale used. All wounds were graded as healed with a grade 1, “excellent-to-good” outcome in both cohorts.

dHACM allografts contain a large number of pro-angiogenic growth factors, chemokines, and cytokines, as well as an array of regulatory molecules.¹² These particular factors can positively influence processes critical for the 3 stages of wound healing: inflammation, angiogenesis, and extracellular matrix production and remodeling.¹³ According to Koob et al, dHACM allografts also stimulate human endothelial cells to produce growth factors and angiogenic cytokines.¹⁴ dHACM has the potential to enhance the initial signals provided by the allograft itself, presumably beyond its life span.¹⁴ Secondary intention healing offers numerous advantages for specific patients and wound types,¹⁵ but it may lengthen recovery time.¹⁶

The data in the current study show that dHACM allograft is effective in healing wounds post-MMS and reduces time to complete healing compared with healing by secondary intention in wounds of similar size, depth, and anatomic location. The outcomes of the current study are similar to those reported by Seaton et al,¹⁷ who reported improved cosmetic outcome and reduced time to wound closure in patients treated with amniotic tissue-derived allograft. However, those authors did not study patients with matched wound location, depth, and size; thus, direct comparison of wound closure rates among matched patients was not possible. Garoufalis et al¹⁸ investigated the role of dHACM in the management of nonhealing wounds of various etiologies and reported markedly expedited wound healing with dHACM. However, Wisco¹⁹ described a case series of patients with relatively superficial lower eyelid defects after MMS that were successfully repaired using dHACM allografts. Although the appearance of scars continues to improve even after a year,¹⁵ cosmetic outcomes were not assessed in any of these studies.

In the current study, there was a statistically significant association between reduced time to complete healing and the use of dHACM allograft in the management of post-MMS defects in specific sensitive anatomic areas. Average time to complete healing in the experimental group was 5.2 weeks ± 2.4 versus 6.5 weeks ± 2.7 in the control group (P = .01). Healing time following dHACM allograft application was 80% faster than that of similar wounds managed by secondary intention. Complete closure was observed in all patients in both cohorts.

While dHACM allograft has demonstrated promising efficacy in promoting wound healing and improving closure rates after MMS, the financial cost should be taken into account. The average wound size in the current study was 4.08 cm², and the cost of each application was estimated to be $651,²⁰ which calculates to an estimated daily cost of $46.5 for each biweekly application. The results of this study and the estimated cost of dHACM treatment suggest that the use of placental allograft in dermatologic surgery may optimize clinical results in a variety of circumstances in appropriately selected patients and wound anatomic locations.

This study has several limitations owing to its retrospective nature. The primary limitation was incomplete documentation for some patients, which reduced the sample size. Furthermore, undisclosed medical history, as well as factors such as functional or nutritional status, potentially may have influenced the outcomes of the study. Future studies should include a larger sample size and an unbiased panel to grade wound outcomes. A longer follow-up period is recommended in future studies because, as noted previously, scars continue to improve in appearance after even 1 year.

The current study provides evidence that dHACM promotes faster wound healing than secondary intention healing in wounds of similar size, depth, and anatomic site. However, there is no difference in aesthetic outcomes of wounds between dHACM and secondary intention healing. The authors of the current study believe that dHACM is a better alternative than traditional secondary intention healing in the management of postoperative wounds.

To the best of the authors’ knowledge, this is the first study to investigate the efficacy of dHACM in the rate of healing postoperative wounds following MMS. Future multicenter, controlled clinical trials are needed to achieve more accurate comparisons of dHACM allograft and secondary intention healing after MMS.