Versatility in the Use of Cadaveric Skin Grafts for Wound Management

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The use of cadaveric skin grafts for burn management has been widely described since it was included in protocols in Philadelphia, Pennsylvania, United States, in 1980.¹ Cadaveric skin grafts provide biological coverage of wounds that serves as a scaffold for the patient's cells to develop a neodermis, while reducing fluid and protein loss, inflammation, pain, and risk of infection, and accelerating wound healing.² This process improves the quality of the wound bed, thus preparing it to receive an autologous skin graft.³

The benefits of the biological coverage of wounds have led to the extension of the use of cadaveric skin grafts for the management of acute and chronic wounds of different etiologies. The current article describes the experience at a single institution of using cadaveric skin grafts in the management of wounds of diverse etiologies.

A retrospective chart review was performed of patients with non-burn wounds of different etiologies that were managed with cadaveric skin grafts followed by subsequent autologous STSG from May 2017 through May 2022 in the Plastic and Reconstructive Surgery Department of German Hospital, Buenos Aires, Argentina. Patients whose wounds were caused by burns were excluded.

Clinical data such as age, sex, comorbidities, etiology, wound location and size, engraftment percentage, and complications were obtained from patients' electronic charts. All patients were informed of the pros and cons of the use of cadaveric skin for the management of their wounds and signed a consent form acknowledging receipt of this information and agreeing to such treatment. All patients gave informed consent for the use of the data collected, including images. The study was conducted following the principles outlined in the Declaration of Helsinki. The affected BSA was calculated based on Pulaski and Tennison's rule of nines, first described in 1949.⁴

All patients underwent an initial surgical procedure under general anesthesia in which the wound was debrided with a scalpel to remove devitalized tissue from the wound surface until vital tissue was reached (Figure 1A, B). The wounds were then covered with cadaveric skin graft obtained from the tissue bank at Hospital Garrahan, Buenos Aires, Argentina.

At the skin bank the initial processing after harvesting the skin consists of washing and soaking the skin in antibiotic solution for 24 hours.⁵ Secondary processing consists of washing the cadaveric skin in saline solution to remove the antibiotic solution, then immersing it in cryopreserving solution (85% glycerol) and packing it in sealed containers for cryopreservation at −80°C. In the final processing stage, the skin is irradiated with gamma rays (25 kGy).⁵

In the current study, the allografts were fixed with titanium staples (Figure 1C). Wound dressings were prepared with silver sulfadiazine gauze, and compression was achieved by placing various standard unpacked gauzes over the silver sulfadiazine gauze and fixing and compressing these against the wound with 2-0 nylon sutures placed at the edges of the graft or with NPWT (XLR8 Plus Negative Pressure Wound Therapy Pump; Genadyne Biotechnologies, Inc). The device was set at −125 mm Hg of intermittent pressure for 5 minutes at 7-minute intervals.

After the cadaveric skin graft had taken to the wound bed, a second procedure was done under general anesthesia to partially remove the cadaveric skin graft (Figure 1D) by scraping it with a scalpel to detach any portion of the skin graft that had not taken to the wound bed and revitalize the neodermis. In cases in which the surface of the neodermis was not considered sufficiently vascularized to take the STSG, it was removed completely. The wound bed was then covered with 0.020-inch STSG obtained with an electric dermatome to replace the epidermal layer lost during epidermolysis (Figure 1E). The STSG was fixed with titanium staples, and the dressings were managed in the same way as in the previous step involving allograft fixation (ie, silver sulfadiazine gauze compressive dressing or NPWT). The STSG donor sites were managed with silver sulfadiazine gauze dressing, which was changed every 48 hours for the first 2 weeks.

After both procedures the dressings were changed every 72 to 96 hours, at which time the wounds were evaluated for epidermolysis, vascularization, and engraftment percentage, as well as for the presence of hematoma, seroma, exudate, and perilesional inflammation. The engraftment percentages used for analysis were those noted 15 days after each procedure. The engraftment percentage was calculated using a transparent grid of 1-cm × 1-cm squares that was placed over the wound. This method was used to calculate the total wound surface in square centimeters, the surface of the graft take in square centimeters, and the engraftment percentage.

In cases in which NPWT was used, this therapy was suspended 7 days after STSG.

The statistical analysis of the results was performed using Stata (version 14.2; StataCorp LLC). Quantitative data were evaluated using the t test. Categorical data were evaluated using the Fisher exact test. The statistical significance level was set at .05.

The study included a total of 25 patients with acute and chronic non-burn wounds of different etiologies that the authors of the current manuscript managed with cadaveric skin grafts and subsequent STSG. The mean patient age was 70.12 years (range, 26–97 years). There were 14 female patients (56%) and 11 male patients (44%). All patients presented with comorbidities, which are described in Table 1. The etiology of the wounds was as follows: venous leg ulcer in 7 patients (28%), traumatic in 5 (20%), multifactorial or unknown in 4 (16%), arterial ulcer in 2 (8%), neoplastic in 2 (8%), infectious in 2 (8%), pressure injury in 2 (8%), and diabetes in 1 (4%).

The mean affected BSA was 1.87% (range, 0.25%–8%). The most frequent location affected was the lower limb, in 16 patients (64%), followed by the talus in 4 patients (16%), the foot in 2 (8%), the scalp in 1 (4%), the forearm in 1 (4%), and the perineum in 1 (4%). NPWT was used in 11 patients (44%).

The mean engraftment percentage of the cadaveric skin graft 15 days after engraftment was 96.6% (range, 70%–100%). The mean time between the cadaveric skin graft and STSG was 32.4 days (range, 12–110 days), with a median of 25 days. The mean engraftment percentage of the STSG 15 days after engraftment was 90.6% (range, 60%–100%). All patients exhibited improvement in local edema and inflammation, reduced secretions, and reduced pain after treatment, as well as acceptable cosmetic results (Figures 1-3).

Two patients (8%) presented with complications related to their wounds and wound management during follow-up. One patient (patient 5) presented with ulcers in both lower limbs resulting from diabetic microangiopathy (affected BSA, 8%). After STSG, the patient experienced delayed healing of the donor area (bilateral thighs), which resolved completely with use of topical acetic acid and vitamin A cream after 4 weeks. Patient 21 presented with a lesion in the left foot of infectious origins (affected BSA, 0.25%), which evolved with hypertrophic scarring that was managed with pressure therapy with silicone sheets. No patients required revision surgery.

The first report on the use of allografts for the management of burns was published by Pollock⁶ in 1871. He grafted his own skin together with that of the patient to manage a burn. In 1980, May and DeClement established the first protocols for the processing and use of cadaveric skin grafts for the management of acute burns.¹ In 1881, Girdner⁷ used cadaveric skin grafts for the management of burns for the first time. Since then, cadaveric skin grafts have been widely used for the management of burns with very good results, which encouraged their use in the management of wounds of other etiologies.

The cadaveric skin graft provides a scaffold of extracellular matrix that promotes wound healing by stimulating migration of the patient's own cells, which create a neodermis² and accelerate the wound healing process.^8,9 Biological coverage of the wound bed reduces the loss of fluids, proteins, and electrolytes by reducing wound exudate, and it protects the wound from desiccation and reduces local pain.¹⁰ This improves the wound bed quality prior to definitive reconstruction,³ resulting in improved cosmesis and functional long-term results, thereby increasing the patient's quality of life.²

The processing of cadaveric skin with glycerol and radiotherapy removes the donor's cells from the skin, resulting in an acellular tissue with low immunogenic potential, thus reducing the chances of rejection.¹ If the skin is not processed adequately and its cellular component remains, when the allograft is vascularized by the host 3 to 4 weeks after grafting, an immune response is generated by the host that rejects the cadaveric skin.¹¹ Processed cadaveric skin graft consists of the extracellular component of the dermis, but without its antigenic capacity; thus, it can be incorporated as part of the extracellular matrix of the neodermis. This neodermis improves the wound bed conditions to receive the STSG.¹² The dermal component may be used as a permanent skin substitute, but the epidermis of the cadaveric skin graft is always lost after graft placement due to epidermolysis; thus, the epidermal layer must be replaced with STSG to complete wound closure and replace all layers of the lost skin.

In the current study, NPWT was used in 11 patients (44%). NPWT aids wound healing by enabling the skin grafts to come into closer contact with the wound bed, potentially improving graft take. Use of NPWT reduces the risk of infection, removes wound secretions and inflammatory factors, promotes fibroblast proliferation, and increases vascularization of the graft.^13,14 The differences between patients who received NPWT and those who received silver sulfadiazine gauze and compressive dressing are noted in Table 2. There was no statistically significant difference between groups based on age, sex, or wound etiology. The affected BSA was greater in the group that received NPWT. The mean allograft take and STSG take was greater in the group that did not receive NPWT; however, these values were not statistically significant. The mean number of days from placement of the cadaveric skin graft to STSG was lower in the group that received NPWT, but the difference was not statistically significant. Shen et al¹⁵ compared the efficacy of NPWT with conventional mechanical fixation of skin grafts and found the overall survival rate of full-thickness skin grafts to be significantly higher in the NPWT group than in the conventional dressing group (88.2% and 57.7%, respectively). Overall STSG survival rates were also greater in the NPWT group, but these values were not statistically significant. The infection rate was lower and fewer complications occurred among patients who received NPWT.

Comparison of the experience in engraftment percentage in the current study with other studies was difficult due to heterogeneity in patient population, etiology, and anatomical location of the injuries, as well as the lack of reporting on engraftment percentage in other studies. Two authors of the current study previously published their experience using cadaveric skin in the management of 22 lower limb ulcers of vascular and traumatic origin, with an average allograft engraftment percentage of 90.9%.¹⁶ Integra Dermal Regeneration Template (Integra LifeSciences Corp) was used to complement allograft treatment in 6 patients; the average skin autograft engraftment percentage was 73.9%. In 1999, Snyder and Simonson¹⁷ reported a greater than 90% average engraftment of all skin grafts used over meshed allografts for the management of lower limb wounds of various origins, an engraftment percentage slightly less than the average reported in the current study. However, only 35% of the patients in Snyder and Simonson¹⁷ received STSG, with the remainder healing by secondary intention. The autologous STSG engraftment percentage was not reported. In a study published in 2001, Munster et al¹⁸ reported an 88% engraftment rate with the use of AlloDerm (AbbVie) and a simultaneous meshed STSG for the management of full-thickness burns. Ryssel et al¹⁹ managed severe burns with MatriDerm (MedSkin Solutions Dr. Suwelack AG), a bovine-based type I, III, and V collagen and elastin-based dermal substitute, and simultaneous STSG; they reported an 83.4% engraftment percentage. Anderson et al²⁰ used meshed STSG in the management of diabetic ulcers in the lower extremity and reported a mean 97% engraftment rate (range, 40%–100%). Barbul et al²¹ performed a retrospective matched cohort study to evaluate the effectiveness of a bioactive split-thickness human allograft compared with standard of care in the management of diabetic ulcers. There was a statistically significant difference in overall healing rate between the control group and the study group (55.9% and 66.8%, respectively). Gurtner et al²² performed a retrospective matched cohort study of lower extremity wounds of multiple etiologies, comparing a bioactive human skin allograft with standard of care. Wounds in the study group were more likely to close compared with wounds in the control group (68.3% and 60.3%, respectively), particularly wounds with exposed structures (64% and 50.4%, respectively) and with a lower recurrence at 6 months (24.9% and 28.3%, respectively). The control group was 2.75 times more likely to require amputation than the treatment group.

Dermal substitutes have been used in the management of chronic wounds. ADM is a dermal substitute derived from autologous and allogenic tissues that undergo a cell removal process to obtain the dermal matrix.²³ ADM is effective for tissue regeneration and wound healing.²⁴ Kim et al²⁵ performed a randomized prospective trial comparing paste-type ADM with standard wound care in patients with full-thickness wounds of multiple etiologies. After 12 weeks, complete wound healing occurred in 76.3% of the patients in the study group, compared with 30.6% in the control group. Brigido²⁶ performed a prospective randomized controlled trial using a human acellular regenerative tissue matrix in patients with full-thickness diabetic ulcers of the lower extremity. At 16 weeks, 85.7% of the patients in the study group had achieved full wound closure, compared with 28.6% of the patients in the control group. ADM provides a favorable environment for cellular proliferation and vascularization, which promote wound healing by a self-regeneration process.^27,28 Interactions between the ADM and the wound bed may result in wound healing by granulation and epithelialization.²⁹

The management of exposed tendons with autologous skin grafts is complex, because the exposed tendon does not provide a quality wound bed that favors graft take. Three patients included in the current study had lower extremity wounds with exposure of the Achilles tendon. With the engraftment of the cadaveric skin graft it was possible to improve the quality of the wound bed, which enabled successful STSG. Hsu et al³⁰ reported an overall success rate of 88.1% in a retrospective case series of 65 patients with acute or chronic wounds with exposed bone or tendon treated with NPWT combined with artificial dermis (Terudermis; Terumo Corp) and second-stage STSG.

The presence of comorbidities tends to compromise graft take. All the patients in the current study had comorbidities: high blood pressure (44%), immunosuppression (36%), diabetes (24%), smoking (16%), systemic oncologic disease (4%), obesity (4%), and other comorbidities (56%). Patients with multiple comorbidities are at risk of decreased graft take and of developing new wounds over time. Management with flaps is associated with increased morbidity of the donor area, longer operating time, and a longer hospital stay.³¹ In addition, the donor area cannot be used for subsequent reconstructions. Despite the high incidence of comorbidities in the current study, a high mean engraftment percentage was obtained (96.6% for cadaveric skin graft and 90.6% for STSG). Cadaveric skin graft can also be used to predict the potential take of an autologous skin graft,^14,32 which can aid in avoiding the risk of generating a donor site for an STSG that has a high possibility of not taking. Cadaveric skin graft with subsequent STSG is a simple and safe alternative with decreased morbidity for the treatment of elderly patients with multiple comorbidities who may require multiple reconstructions of new wounds over time.

The complication rate in the current study was 8% (2 patients). In 1 case, the patient experienced delayed healing of the donor area (bilateral thighs), which resolved completely with topical acetic acid and vitamin A cream. Another patient evolved with hypertrophic scarring which was treated with pressure therapy with silicone sheets.

One limitation of the current study is its retrospective nature. In addition, the small sample size does not allow for determination of statistical significance either when comparing patients who received NPWT with those who did not or when comparing different wound etiologies. The study also lacked a control group in which STSG was applied directly to the wound bed without using cadaveric skin, which would have allowed comparison of engraftment percentages with these 2 techniques.

Cadaveric skin graft followed by subsequent STSG is a simple, safe, and effective alternative for the management of complex wounds of diverse etiologies, with a mean engraftment percentage of 96.6% for cadaveric skin and 90.6% for STSG in the current study. Cadaveric skin graft can be used as an intermediate step in wound reconstruction to evaluate the potential take of an STSG while simultaneously improving the quality of the wound bed by providing biological coverage. In the current study, NPWT did not increase graft take significantly. This technique for use of cadaveric skin graft with subsequent STSG is particularly useful in patients with multiple comorbidities who are at risk of recurrence and of developing multiple wounds during their lifetime, because it minimizes morbidity at the donor site, which can then be reused. Further studies are needed to determine whether a statistically significant difference in engraftment percentage exists between NPWT use or not and to compare results of the use of cadaveric skin grafts in different wound etiologies.

Authors: Lucila M. Olivera Whyte, MD; Matías E. Izquierdo, MD; Diana M. Gutiérrez Pachón, MD; Juan Achával Rodríguez, MD; and Gustavo E. Prezzavento, MD

Affiliation: German Hospital, Buenos Aires, Argentina

Disclosure: G.P. is a speaker for Promedon-Integra LifeSciences for Argentina. The remaining authors disclose no financial or other conflicts of interest. No funding was received for this work.

Ethics: All patients provided informed consent for inclusion before they participated in the study, and patients whose photographs were used in the manuscript provided written consent for their use. The study was conducted in accordance with the Declaration of Helsinki.

Manuscript Accepted: July 1, 2024

Correspondence: Lucila M. Olivera Whyte, MD; German Hospital, 1640 Pueyrredón Avenue, Buenos Aires City, C1118AAT, Argentina; lolivera@hospitalaleman.com