Clinical Experience and Best Practices Using Epidermal Skin Grafts on Wounds

Over the years, autologous skin grafting has been used extensively to achieve wound closure, optimize a functional scar, and improve aesthetic outcomes for the patient. Although a vast majority of the literature is on the use of full-thickness and split-thickness skin grafts, epidermal skin grafts (ESGs) have emerged as a viable option in the reconstructive ladder when only the epidermal layer is needed. These grafts are distinct from other types of autologous skin grafts in that they can be harvested without anesthesia and leave minimal or no scarring at the donor site. In order to explore the use of ESGs in the continuum of primary wound closure, a multidisciplinary expert panel convened in October 2014, in Las Vegas, NV, to review the scientific basis and clinical uses of epidermal grafting. This publication provides an overview of epidermal grafting, recommendations for graft application, and potential roles for its use in wound care and closure.

Autologous grafting remains a critical component of the reconstructive ladder for both acute and chronic wounds, and the procedure can be performed in a variety of settings, including in the operating room (OR) and wound care clinic.¹ While grafts are typically considered for their mechanical function as skin transplants, they may also serve as a biological stimulus for healing.² Regardless of the mechanism of action, the goals of performing autologous skin grafting include wound closure with the restoration of missing or damaged skin and, depending on the type of graft used, optimization of functional and aesthetic outcomes. Achievement of these goals may heal wounds and ease a patient’s physical and emotional pain.

Grafts are often categorized by the depth of the donor skin transferred. Full-thickness skin grafts (FTSGs) contain the entire epidermis and dermis with preservation of the adnexal structures. Full-thickness skin grafts can prevent wound contracture due to the depth of skin transplanted, which may lead to improved aesthetic or cosmetic outcome. However, drawbacks of using FTSGs include the need for primary closure and potential scarring at the donor site. Due to the amount (ie, thickness) of tissue transferred, the recipient area must be able to sustain the donor skin; thus, an indeterminate percentage of successful engraftment may occur. Local or regional anesthesia is typically needed during harvesting.

Split-thickness skin grafts (STSGs) contain the epidermis and partial-thickness dermis containing only part of the adnexal structures. Typically, STSGs do not prevent wound contracture. Therefore, as opposed to a goal of aesthetic enhancement of the healed wounds, the major goal of STSGs is to restore the functional integrity of the skin in the recipient site. However, drawbacks of the procedure include some donor site scarring, pain, and the need for anesthesia. However, due to their relative thinness compared to FTSGs, STSGs are preferable for compromised recipient sites (eg, most chronic wounds). Often, there is a high percentage of initial successful engraftment, but a number of STSGs may fail over time, especially in high-pressure areas, such as the plantar foot, based on author experience.

Epidermal skin grafts (ESGs) consist of only the epidermal layer of the skin and provide epidermal cells (eg, keratinocytes and melanocytes) to the recipient area. They do not prevent wound contracture and, therefore, like STSGs, the major goal of epidermal grafting is to restore the functional integrity of the skin in the recipient site. However, distinct from other forms of skin grafting, ESGs do not require anesthesia to harvest, cause minimal or no scarring, and thus, leave little or no donor site morbidity.^3,4 While graft take by epithelialization may occur, stimulation of healing is often observed, as indicated by the improved wound bed appearance and wound closure.^2-5

A new technique for epidermal harvesting has recently been developed that allows donor site harvesting to be easily performed in settings other than the OR. This development eliminates the risk of anesthesia-related complications and makes epidermal grafting more practical and less expensive to obtain. Epidermal skin grafts offer an alternative to traditional autografts when only the epidermis is needed and use only a minimal amount (ie, thickness) of autologous tissue from the donor site. Good wound bed preparation (ie, adequate granulation tissue formation and management of bioburden) is necessary for reepithelialization to be able to occur with the use of ESGs.⁶ These grafts are also dependent upon the recipient environment to determine their eventual phenotypic state.

An expert panel of physicians from various fields (ie, podiatry, plastic surgery, dermatology, and wound care centers), convened in October 2014 to review the scientific basis and clinical uses of epidermal grafting. The purpose of this paper is to discuss the position of epidermal grafting in the continuum of primary closure. Additionally, this publication provides an overview of epidermal grafting and its potential roles in wound care and closure. The authors have also provided cases demonstrating the successful use of ESGs over various wound types.

In addition to dividing skin grafts based on the thickness of the skin harvested, skin grafts can also be categorized based on the technique of donor site harvesting. Free-hand methods, such as pinch or punch grafting—in which skin is harvested using a scalpel, other type of blade, or a punch biopsy tool—are typically employed when only a small graft is needed. When a larger amount of donor skin is harvested, powered dermatomes are used to increase efficiency. Often, these grafts are meshed prior to placement to expand the size of the graft and to allow any fluid or exudate in the recipient site to escape through the interstices so as not to compromise graft-wound bed interaction.

Various methods of transferring epidermis (often in addition to dermal tissue) have been developed and expanded throughout the years since Jacques-Louis Reverdin first used small, full-thickness skin pieces as grafts for wound healing in 1869.⁷ In 1964, Kiistala and colleagues⁸ introduced suction blister epidermal grafting (SBEG) as a method for obtaining epidermal sheets. The technique has since been modified and expanded for use on depigmented lesions and wounds,⁹ including treatment of vitiligo,^10-14 lesions of chronic discoid lupus erythematosus,¹⁵ and acute and chronic wounds.^16-21 The clinical success of SBEG has led to other epidermal grafting techniques, such as cultured epidermal autografts (created when an epidermal graft is grown in the lab from keratinocytes) for use over burns and wounds.^22,23 The results from these early experiences have demonstrated SBEG to be cost effective and cause minimal donor site discomfort and morbidity. Unfortunately, SBEG methods historically lacked reliability or reproducibility and were cumbersome and time consuming. This is because the methods used for harvesting the epidermal skin included syringes, 3-way connectors, vacuum pumps,^16-19 suction cups and pumps,^20,21,24 and thermal-regulated suction chambers connected to vacuum sources.^25,26

Recently, an automated, minimally invasive tool (CelluTome Epidermal Harvesting System, KCI, an Acelity company, San Antonio, TX) for harvesting ESGs has been developed that combines suction at slightly increased temperatures to consistently harvest epidermis. The system consists of a control unit, vacuum head, and harvester. The harvester is positioned on the skin surface of a selected extremity, usually the thigh, and secured with a hook and loop fastener strap; the vacuum head is then applied to the harvest site. After microdome formation and harvesting, an adhesive dressing is used to transfer the grafts to the recipient site. These ESGs have shown in a study of healthy volunteers (n = 15) to contain viable cells after separation within the lamina lucida at the dermal/epidermal junction and to secrete growth factors important for wound healing. Keratinocytes and melanocytes from these grafts proliferated in culture, and type IV collagen has been found to be present in these grafts.^27,28 In addition, minimal donor site morbidity is caused by the procedure. In the same study, donor sites healed with minimal irritation and 76%-100% of donor sites had the same appearance as the surrounding skin by 14 days post harvesting.²⁷ There was minimal discomfort during harvesting of the epidermal microdomes without the use of anesthesia.²⁷Table 1 and continued summarizes the literature on the use of epidermal grafting over wounds.

Interestingly, a comparison of donor sites showed that 1 harvested by pinch grafting (Figure 1A) had visible injury, while those harvested by the automated epidermal harvesting system (Figures 1B-1D) had minimal injury (R. S. Kirsner, MD, unpublished data). Furthermore, dermoscopy images (Figure 2) showed healing of a single microdome harvested with the epidermal harvesting system on day 2 (R. S. Kirsner, MD, unpublished data). 

An approach to wound closure that includes the use of ESGs is proposed in Figure 3. This begins with a thorough assessment of the patient and wound²⁹ to assure comorbidities are addressed and the patient has requisite ability to heal, such as adequate nutrition, vascular supply, and absence of soft tissue infection or osteomyelitis, which will allow for optimization of patient outcomes. Established wound bed preparation and standard care (eg, compression and offloading) treatment protocols for wounds, such as diabetic foot ulcers (DFUs) and venous leg ulcers, are recommended to initially prepare the wound bed for ESGs. 

The criteria for a graftable wound bed should include the following: adequate granulation tissue formation to support living cell therapy, controlled drainage, and controlled bioburden. After ESGs have been chosen as the wound closure strategy, periodic assessments should occur to determine whether goals of therapy (eg, complete healing, stimulus to healing, limb preservation, and significant wound size reduction) have been met.

The following information provides guidance on applying ESGs and is based on the experience of the expert panel (Table 2). 

Prior to application of epidermal skin grafts. Critical to the success of epidermal grafting, wounds should be properly selected for grafting. Grafts may not be as effective in highly proteolytic or inflammatory wound environments; therefore, wound bed preparation is of utmost importance and should include debridement, infection management, and reduction of bioburden. While often not feasible, ideally, quantitative or semiquantitative wound cultures would help guide appropriate time to apply ESGs, but conceptually, wound bacterial burden should be minimized prior to applying ESGs, and a significant amount of granulation tissue should also be present.

Application of epidermal skin grafts. No pretreatment is required at the donor site. The donor site may be warmed and/or moistened prior to applying the harvesting device to speed up time to microdome formation. These warming/moistening techniques may be helpful in young patients and in individuals with darkly pigmented skin. The harvested microdomes can be transferred using a film dressing that is pierced several times or a nonadherent silicone dressing, both of which can help manage wound exudate and prevent shifting of the grafts from the wound bed. Skin adhesives may also be used around the periwound when using the film dressing. Double-density ESGs may be created by cutting the transfer dressing and reorienting it over the harvest, so that all microdomes are on the dressing, which can then be applied over the wound.

Secondary dressings can, and should, be used over the wound after application of ESGs. These secondary dressings include compression and bolstering materials (eg, foam dressings, gauze wraps), compression wraps, and offloading devices including total contact casting depending on the wound etiology and location. The purpose of the bolster is to keep the transfer dressing in contact with the wound, increase the surface area contact, and help prevent shearing. Negative pressure wound therapy (NPWT) (V.A.C. Therapy, KCI, an Acelity company, San Antonio, TX) can also be used to improve graft/wound bed contact.

After application of epidermal skin grafts. For at least 1 week, ESGs should not be disturbed in any way and primary dressings should not be removed, although secondary dressings can be changed within 1 week, if needed. At the first few weekly dressing changes, debridement should not be performed, unless there is any negative change in the wound bed appearance, such as excessive maceration, infection, or necrosis. Given the thinness of the graft, graft take may occur but may not be visible for up to 3 weeks after application.

Case study 1. A 52-year-old male patient presented to San Francisco General Hospital (San Francisco, CA) with a soft tissue foot infection (Figure 4A). After presentation, the patient was found to be a severe diabetic. The wound was initially debrided (Figure 4B) and NPWT was applied periodically for approximately 2 weeks (Figure 4C). At this time, a STSG was applied over the wound (Figure 4D). However, at 3 weeks postapplication, the STSG sloughed off the wound (Figure 4E) and alginate dressings were then applied. The patient refused a second STSG application; therefore, ESGs were applied (Figure 4F). At 3 weeks postapplication of ESGs, a second application occurred (Figure 4G). Figure 4H shows the closed wound at 6 weeks after second application. 

Case study 2. The patient was a 61-year-old male with diabetes and cellulitis who presented to Columbus Podiatry and Surgery Inc (Columbus, OH) with a traumatic injury to the right leg (Figure 5A). The wound had been present for 14 weeks with previous treatments including an Unna boot and NPWT. Epidermal skin grafts were harvested from the patient’s thigh and transferred to the wound site using a film dressing. A bolster dressing using gauze and a self-adherent wrap was used to hold the ESGs in place. During the 3 weeks postgrafting, the wound showed improvement in healing (Figures 5B-D). A second application of ESGs was then applied (Figure 5E). At 5 weeks after the second application of ESGs, the wound was closed (Figure 5F). Figure 5G shows the donor site 1 week after harvesting, and Figure 5H shows the donor site 3 weeks postharvesting. 

Case study 3. The patient was a 90-year-old male who presented to the University of Miami Hospital Wound Center (Miami, FL) with a postsquamous cell carcinoma excision. He had a past history of venous insufficiency with percutaneous mechanical thrombectomy compression and bilayered living cellular construct. He presented with an ulcer of 4-month duration (Figure 6A) with prior treatment of compression, zinc sulfate, pentoxifylline, and arginine. Epidermal skin grafts were harvested from the thigh and applied over the wound site. A foam dressing was used as a bolster over the ESGs. At 4 weeks postapplication, epithelialization around the wound edges was observed (Figure 6B). At 10 weeks postapplication, the wound was fully closed (Figure 6C). 

Case study 4. A nondiabetic patient presented to St. Luke’s-Roosevelt Hospital Center (New York, NY) with a heavily infected vasculitic wound with no ischemia and minimal venous insufficiency; however, the lateral leg ulcer was very painful. The patient was taken to the OR, and the wound was debrided. Instillation therapy was used for 7 days, followed by application of an acellular human dermis bolstered with standard NPWT for 4 days (Figure 7A). After 6 weeks of additional wound bed preparation, ESGs were applied (Figure 7B). The wound showed improvement and some epithelialization was observed (Figure 7C). A second application of ESGs occurred at 35 days after initial application (Figure 7D). The wound continued to heal and showed further epithelialization over the following weeks (Figures 7E-7G). At approximately 17 weeks following the second application of ESGs, the wound was closed (Figure 7H). 

Case study 5. The patient was a 59-year-old male who presented to Mount Nittany Wound Center (State College, PA) with a wound on the plantar surface of the right foot. There was periwound erythema with significant slough and necrotic tissue present on the wound base. The patient had been seen by other physicians 3 weeks prior with past treatments of antibiotics, debridements, and standard gauze dressings. The patient’s medical history reported atrial fibrillation, hyperlipidemia, hypertension, colitis, diabetes, hypothyroidism, and bladder cancer. After examination at the wound clinic, diagnosis was a Wagner grade 2 DFU (Figure 8A), and extensive debridement was performed to remove slough, subcutaneous tissue, and necrotic tissue (Figure 8B). Negative pressure wound therapy was initiated at -125 mm Hg continuous pressure. After 1 week, granulation tissue was present in the wound (Figure 8C) and continued to increase after 4 weeks of NPWT (Figure 8D). At 10 weeks, NPWT was discontinued, and the wound was fully granulated (Figure 8E). Two weeks later, the wound was prepared for epidermal graft application (Figure 8F). At 1 week postapplication, epidermal buds were present within the wound (Figure 8G). At 2 weeks postapplication, epithelialization was noted (Figure 8H). At 3 weeks postapplication, epithelialization had increased (Figure 8I). At 4 weeks postapplication, the DFU was closed (Figure 8J). 

Skin grafting has been used for centuries to help heal wounds. New grafting tools have been developed, and a novel device is now available that allows for consistent harvesting of autologous epidermis without the use of anesthesia in settings other than the OR. Early experience with epidermal grafting has been positive. Benefits include the ability to treat a variety of wound types, harvest additional ESGs due to limited, if any, donor site morbidity, and reapply autologous skin as needed; however, unanswered questions remain.

A study of 48 patients showed that ESGs assumed the phenotype of the recipient site where they were placed, while STSGs and FTSGs did not.² The study found palmoplantar wounds (n = 14) that healed with epidermal sheet grafts had histology and keratin protein expression comparable to unwounded plantar skin, while FTSGs and STSGs used for 34 other palmoplantar wounds retained the characteristics of the donor site (n = 17 for nonpalmoplantar skin and
n = 17 for palmoplantar skin) from which they were harvested.³⁰ Given the durability of a cohort of palmoplantar wounds closed with epidermal sheet grafts, these wounds may have better long-term outcomes than wounds closed by other methods.³⁰

A key question concerning epidermal grafting is whether the tissue donated (ie, keratinocytes, melan-ocytes, or collagen IV) remains in the wound bed or is used as a substrate to stimulate surrounding tissue to close the wound. Clinicians must keep in mind this may be dependent on the characteristics of the recipient wound site. In the highly prepared wound, the cells may persist, while in a less-prepared wound, they may act in a more sacrificial fashion, secreting growth factors and other cellular signals to improve wound healing. It is possible to use animal (ie, porcine) models with radiolabeling of the donor site prior to harvesting and then following the implantation site to help clarify this question.

Additionally, validating ease of use and patient satisfaction with epidermal grafting would be of interest. Studies evaluating optimal transfer dressing (ie, adhesive, nonadherent silicone, or foam dressing) also warrant further study. For example, a foam dressing may be more appropriate for exudative wounds, while an adhesive dressing may be preferable for low-drainage wounds.

The authors suggest that ESGs are clinically useful in 2 different manners. One way to envision use of ESGs is in a fashion similar to STSGs, such as in case study 5, as a single application that works to reepithelialize the wound and provide coverage. The combination of graft take and stimulus to healing could be envisioned in a well-prepared chronic wound such as case study 3, or in an acute postsurgical wound such as case study 1. Alternatively, due to ease of harvesting, low donor site morbidity, and patient comfort, ESGs may be used in a serial application as seen in case studies 2 and 4. While the optimal frequency of reapplication is not clear, early reapplication prior to 1 month may not allow visualization of graft take. With serial use, the early applications may function as wound bed preparation, and the final graft may reepithelialize the wound. Moreover, since there is minimal-to-no donor site morbidity, the use of ESGs does not “burn any bridges” or preclude the use of a STSG or a more complex procedure at a later time. This represents a different algorithm of care.

While this manuscript has provided some early guidelines for epidermal grafting, the eventual goal of the clinician and the underlying wound type will determine the timing and frequency of epidermal graft application. Similar to STSGs, the technique used and the application indication are likely to vary greatly among physicians. Controlled clinical studies with larger patient populations are warranted to determine efficacy and cost effectiveness of epidermal grafting in different wound types.

The authors would like to thank Julissa Ramos and Ricardo Martinez from Acelity for manuscript support and preparation.

Affiliations: ¹Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, FL; ²Charcot and Reconstructive Foot Program, St. Luke’s Hospital, Quakertown, PA; ³Columbus Podiatry and Surgery Inc, Columbus, OH; ⁴Department of Vascular Surgery, Mount Sinai Roosevelt Hospital, New York, NY; ⁵St. John Health System, Tulsa, OK; ⁶Central Texas Wound Healing Associates, Killeen, TX; ⁷Department of Plastic Surgery at Rhode Island Hospital, Providence, RI; ⁸Valley Presbyterian Hospital, Los Angeles, CA; ⁹Mount Nittany Center for Wound Care, State College, PA; and ¹⁰San Francisco General Hospital, San Francisco, CA

Correspondence:
Robert S. Kirsner, MD, PhD
Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine
1600 NW 10th Ave, RMSB, Room 2023-A, Miami, Florida 33136
RKirsner@med.miami.edu

Disclosure: The authors all have a consulting agreement with Acelity, but received no funding for the article.