Efficacy of Epidermal Skin Grafts Over Complex, Chronic Wounds in Patients With Multiple Comorbidities

Background. Epidermal skin grafting presents an alternative to traditional autografts since only epidermal skin is harvested from the donor site. Split-thickness skin grafts are associated with difficulties at the donor site, including excessive pain, delayed healing, fluid loss, and unsatisfactory cosmetic results — all exacerbated in patients with comorbidities. A new automated epidermal harvesting tool (CelluTome Epidermal Harvesting System, KCI, an Acelity company, San Antonio, TX) involves concurrent application of heat and suction to normal skin to produce epidermal grafts. This article outlines the author’s experience using this automated epidermal harvesting tool to harvest epidermal grafts and apply them on 23 chronic lower extremity wounds of patients with multiple comorbidities. Methods and Materials. Vacuum and heat were applied until epidermal microdomes were formed (30-45 minutes); an epidermal microdome array was collected onto a transfer dressing and applied over the wound. Results. The automated harvesting tool yielded viable epithelium with every use. In addition to the epidermal skin graft, 16 of 23 wounds (70%) received adjunctive wound treatment, including negative pressure wound therapy, hyperbaric oxygen therapy, and/or regenerative tissue matrix. The average reepithelialization rate was 88.1% during a mean follow-up period of 76.4 days; no use of an anesthetic/operating room was required for the procedure. All donor sites were completely healed within 2 weeks without complications or scarring. Conclusion. Epidermal skin grafting provided a simplified, office-based grafting option with no donor site morbidity, and assisted in closure or size reduction of chronic wounds in this series.

Split-thickness skin grafts (STSG) are commonly used in burn reconstruction and to close both chronic and acute surgical wounds. However, STSGs involve a painful harvesting procedure that typically necessitates use of anesthesia and an operating room, as the dermatome harvester raises the graft in the plane between the papillary (superficial) and reticular (deep) dermis, leaving the sensory nerves and dermal appendages of the reticular dermis exposed. Leaving these appendages behind aids with regrowth and donor site healing, yet it causes significant postoperative pain. In addition, healing is often delayed by donor site bleeding, infection, and pruritis.¹ In some cases, STSGs result in a visible, and even pathologic, scar. 

Epidermal skin grafting offers an alternative to traditional autografts when only epidermis is needed for superficial wounds. Because only the epidermal skin layer is harvested from the donor site, epidermal skin grafting avoids many of these donor site complications. In addition, anesthesia and an operating suite are not needed, which is particularly advantageous to the wound center patient who presents a high surgical risk, is often on anticoagulation medications, and suffers from multiple chronic medical conditions.

Epidermal grafting using suction blisters on normal human skin was pioneered by Kiistala and Mustakallio² in 1964, and later applied by Falabella³ to treat the stigmata of vitiligo. Since then, autologous suction blister epidermal grafting (SBEG) has become an established technique for treatment of recalcitrant, stable vitiligo and other secondary leukodermas.^4,5 More recently, there have been a few reports^6-8 of SBEG used to treat hard-to-heal wounds, including burns and lower extremity ulcers. 

Suction blister epidermal grafting techniques induce a plane of cleavage through the epidermis at the lamina lucida, which has been associated with irregular hemidesmosome disruption as well as the formation of cytoplasmic vacuoles within many keratinocytes.⁹ The basic structure of the epidermis remains intact and the dermis remains undisturbed.⁹ Success of epidermal grafting thus depends upon precise separation at the dermal-epidermal (DE) junction and transfer of the entire, intact basal layer to the recipient site. 

Traditionally, SBEG has involved a negative pressure apparatus producing -300 to -500 mm Hg of pressure to normal skin to promote the formation of multiple epidermal blisters and has been achieved with various instruments including: syringes and a 3-way stopcock, suction pump and suction cups with a 1-way check valve, and an oil rotary vacuum pump with a manometer connected to suction cups. Blisters are typically removed with scissors or a scalpel and then secured over the prepared recipient site.¹⁰ Conventional SBEG techniques have been described as cumbersome, time-consuming, and inconsistent.^5,8 Larger syringes may take hours to create blisters, and smaller syringes produce blisters that may be difficult to maneuver.^.11 Syringe methods can also require multiple sittings, and inadequate handling of the graft can lead to tearing and improper orientation, causing graft failure. Use of these manual suction methods has thus been somewhat limited in clinical practice due to lack of an automated, standardized, and reproducible technique.

An automated epidermal harvesting system (CelluTome Epidermal Harvesting System, KCI, an Acelity company, San Antonio, TX) is now commercially available for harvesting epidermal skin grafts in an office or outpatient setting. This epidermal harvesting system consists of a reusable control unit, reusable vacuum head, and disposable harvester. Both heat and suction are applied concurrently to normal skin to induce epidermal microdome formation. Microdomes are harvested by activating a handle that sets the harvester blade in motion, and a transparent thin film dressing is used to collect and transfer epidermal grafts onto the recipient site. 

Up to 128 epidermal microdomes can be harvested with the system within 30–45 minutes, and no surgical training is needed.^10,12 The automated epidermal harvesting system has been shown to obtain uniformly viable autologous microdomes at the dermal-epidermal junction with minimal pain and donor site healing in 2–3 weeks.^12,13 This case series reports the author’s experience using this automated epidermal harvesting system for harvesting epidermal grafts for placement over lower extremity wounds in a wound center population.

Patient and wound characteristics. A retrospective record review was performed of consecutive outpatients who received at least 1 epidermal graft harvested with the automated harvesting system between April 1, 2014 and October 21, 2014. All patients were at least 18 years of age and demonstrated recipient sites that were optimized for skin graft closure. Recipient wound beds demonstrated healthy granulation devoid of bacterial infection. Patients with active soft tissue infection or untreated osteomyelitis, active malignancy in the wound bed, poorly controlled or uncontrolled lymphedema, peripheral arterial disease with untreated but correctable disease, worsening/unstable venous stasis disease, and wounds with bare tendon and bone — devoid of peritenon and periosteum, respectively — were excluded from the review. Wounds that did not initially present as optimized were thoroughly cleaned with sterile saline and a gauze 4 in x 4 in pad prior to graft placement and debrided as needed and wound etiologies were addressed. 

Wounds that met criteria were selected for epidermal grafting. The epidermal grafting procedure was explained to each patient and informed written consent obtained. Any complaints of pain, intolerance to the harvesting procedure or subsequent bolster dressing, or any desire to abort the grafting procedure at any time allowed the patient to continue standard wound therapy or an alternative procedure to facilitate wound closure. Noncompliant patients were included in the analyzed data set.

Epidermal graft harvesting. The patient’s inner thigh was prepped as a donor site by clipping hair as necessary; surgical clippers (not razors) were used to avoid epidermal trauma and lessen the chances of infection from abrasions. The donor site was then cleansed with 70% isopropyl alcohol. A sterile harvester was secured around the prepared inner thigh, and the vacuum head was snapped onto the harvester with tubing facing up. The automated system was initiated and the vacuum ( -400 to -500 mm Hg) and heat (37°C to 41°C) were applied to the donor site until epidermal microdomes were formed. Development of epidermal microdomes was observed through the window of the harvester head (Figure 1). 

When it was determined via visual observation that epidermal microdomes were fully formed, the vacuum head was detached from the harvester and an adhesive thin film dressing (Tegaderm, 3M, St. Paul, MN) or nonadhering silicone dressing (Adaptic Touch, Systagenix, an Acelity company, San Antonio, TX) was inserted into the harvester. Microdomes were harvested by activating the harvester’s blue handle to set the blade in motion. A 5 cm x 5 cm epidermal microdome array was collected on the transfer dressings and transferred onto the recipient site. A bolster overlay dressing or negative pressure wound therapy (NPWT) system with a black foam dressing (V.A.C. Therapy and V.A.C GranuFoam Dressing, KCI, an Acelity company, San Antonio, TX) was placed over the epidermal graft to secure it in place. 

The donor site was covered with an adhesive transparent film, which was removed after 24 hours. After 1 week, the transfer dressing was removed from the recipient site and percent reepithelialization was noted during the follow-up period. All wounds were dressed and analyzed at weekly intervals by the same plastic surgeon.

Epidermal microdomes formed after 30–45 minutes with the epidermal harvesting system and were placed on 23 chronic wounds in 22 patients — 7 females, 15 males, with an average age of 61.6 years. Multiple comorbidities were present in 20 of 22 patients (Table 1). Wound locations and types are listed in Table 2. Nineteen wounds received 1 epidermal graft and 4 received 2 grafts; time between the 2 epidermal grafts was 35 days for the 4 wounds that underwent a second application. 

Several wounds were treated with adjunctive therapies including regenerative tissue matrix (Graftjacket, Wright Medical Technology, Inc, Memphis, TN) (n = 6), NPWT (n = 11), and hyperbaric oxygen therapy (n = 9) (Table 3). Five patients received regenerative tissue matrix at least 3 weeks prior to epidermal graft placement, and 1 patient received regenerative tissue matrix 1 month after initial epidermal skin graft placement, prior to regrafting. 

Varying levels of patient noncompliance were reported in 6 patients. In 2 patients, complete graft loss occurred due to patient noncompliance. Of these 2 patients, 1 was noncompliant with lymphedema therapy and refused pressure wraps; the second patient removed the NPWT system and avulsed the epidermal graft. Because graft failure in these cases was largely caused by patient noncompliance, these 2 records were not included in the final analysis. Average reepithelialization rate of the remaining 21 wounds was 88.1% during a mean follow-up time of 76.4 days. Reepithelialization rates are summarized in Table 4. No use of anesthetic or an operating room was required for the procedure. All donor sites were completely healed within 2 weeks without complications or scarring. 

Three cases from the analyzed dataset are detailed further and included to illustrate the use of epidermal grafting for lower limb wound closure.

Case study 1. A 67-year-old female presented with a nonhealing ischemic ulcer with an exposed Achilles tendon 2 weeks following a revascularization procedure (Figure 2A). The patient had a history of peripheral arterial disease, ongoing tobacco use, and noncompliance with wound care therapy. The patient’s right medial thigh was prepared with alcohol and the epidermal harvesting system was used to obtain an epidermal graft. The epidermal microdomes were secured to an adhesive film dressing, harvested, and then transferred to the granulating recipient bed on the posterior calf. Sheets of regenerative tissue matrix were placed over areas of exposed Achilles tendon and bolstered in place with a nonadherent silicone dressing and posterior splint (Figure 2B). Reepithelialization occurred over the wound and tendon within 6 weeks of epidermal grafting and regenerative tissue matrix (RTM) (Figure 2C). 

Case Study 2. An 85-year-old male presented with a dehisced surgical wound with indwelling hardware and exposed tendon on the dorsal aspect of the foot (Figure 3A). The patient had a history of dementia and noncompliance. The wound was debrided and cleaned, and an epidermal skin graft was harvested and placed over it. A nonadhering silicone layer was used to bolster the graft (Figure 3B), and the patient was immobilized in a posterior splint. After 7 days, the silicone layer was removed. The wound was fully reepithelialized 3 weeks postepidermal graft placement (Figure 3C). 

Case Study 3. A 63-year-old male with a history of stage IV melanoma of his plantar foot (Breslow depth 1.6 cm) and Campisi stage III lymphedema of his corresponding lower extremity with bulky inguinal and pelvic lymphadenopathy underwent wide excision and pelvic lymphadenectomy, creating a 4 cm x 5 cm plantar defect (Figure 4A). The RTM was placed intraoperatively to cover the exposed periosteum and peritenon and encourage granulation (Figure 4B). Two months after placement of the RTM, an epidermal skin graft was harvested in the outpatient clinic and placed over the wound (Figure 4C). One month postepidermal skin graft placement, the ulcer was 100% reepithelialized (Figure 4D). 

In this case series, the commercially available automated epidermal harvesting system produced uniform epidermal skin grafts for use over chronic lower extremity wounds. The average reepithelialization rate was 88.1% during an average follow-up of 2.5 months. Approximately half of the wounds in this series closed completely, and a 50% to 99% size reduction was documented in the remaining wounds. There were no observed donor site complications or notable scarring during the duration of the study, and all donor sites were healed by 2 weeks. 

This 22-patient retrospective analysis represents the largest consecutive patient series to date describing the use of epidermal grafting in a variety of wound types. Use of epidermal grafting via the new epidermal harvesting system has been described in several smaller case series.^14-16 Serena et al¹⁴ reported the outcomes of 7 patients with longstanding lower extremity wounds that were treated with epidermal grafts followed by a 2-layer compression. Of the 7 wounds, 6 improved or achieved complete closure in 4 weeks. One 2-year-old thigh wound failed to demonstrate improvement, which may have been due to an inability to secure the graft.¹⁴ Another pilot series by Gabriel et al¹⁵ described epidermal grafts in 4 patients with 4 wounds: a heat burn to a radiated breast, scalp melanoma excision site, chronic diabetic foot wound, and a wound created after removal of a sacral tattoo.¹⁵ A 100% reepithelialization occurred in 3 of 4 wounds. A 50% reepithelialization and wound size reduction was noted for the remaining 8-year-old chronic diabetic foot wound at the 2-month follow-up. All donor sites healed completely without scarring.¹⁵  

Use of epidermal skin grafts has also been reported in a series of 5 patients with recalcitrant lower extremity ulcers diagnosed as pyoderma gangrenosum.¹⁶ Absorbent foam was applied over the epidermal grafts, followed by compression. Three of the wounds achieved 100% reepithelialization — the first at 5 weeks, second at 7, and third at 12. The other 2 patients showed a reduction in ulcer size of 64% and 99%, respectively, within 8 weeks. All patients reported minimal pain associated with the procedure, and all donor sites healed within 1 week.¹⁶ The data in this report are similar to these smaller case series with respect to wound closure rates and donor site healing times.  

The exact mechanisms of epidermal graft incorporation are not known. Costanzo et al⁷ postulated that a major effect appears to be a stimulation of epithelialization from the edge of the ulcer with a visible translucent epidermal outgrowth. Other authors^14-16 reported that epidermal grafts did not appear to “take” to underlying granulation tissue, but rather, reepithelialization occurred from the wound edges. Costanzo et al⁷ suggested this wound-edge effect could be mediated by growth factors produced by grafted keratinocytes. Indeed, a recent in vitro examination of epidermal grafts obtained with the epidermal harvesting system showed that migratory basal layer keratinocytes and melanocytes were proliferative in culture. Examination of intact microdome roofs from healthy human samples (n = 3) demonstrated viable basal cells actively secreted key growth factors important for modulating wound healing responses, including vascular endothelial growth factor, hepatocyte growth factor, granulocyte colony-stimulating factor, platelet-derived growth factor, and transforming growth factor alpha.¹³ 

As with STSG, proper patient selection and compliance are key elements in successful epidermal grafting. Patient selection, graft harvesting, and follow-up examinations were performed by a single board-certified plastic surgeon, well experienced with performing both split- and full-thickness skin grafts. As with all grafts, wound bed coaptation, infection management, hemostasis, and maintenance of a proper graft environment are key factors in graft take. This author observed epidermal grafts to be most successful under conditions of drainage and exudate control and patient compliance, with adjunctive NPWT to assist granulation and control fluid before graft placement as well as a bolster following placement. Avoiding contact with the dermal layer during epidermal harvesting resulted in minimal to no bleeding, minimal to no scarring, and minimal donor site pain in these patients. This study failed to quantify pain, as this was beyond the scope of this feasibility study; however no patients verbalized any complaints of pain, no harvests were halted due to complaints of pain, and no local anesthesia was required. 

Though all grafts and follow-up examinations were performed by a single surgeon for the sake of standardization, no specialized surgical training is required for this technique. However, consistency in clinical care did lead to some key wound observations and modification of protocol. For example, the transfer dressing used with the system must facilitate easy transfer of the microdomes in the proper orientation to the recipient site without tearing or avulsing the microdomes. The author initially used an adhesive thin film dressing fenestrated with a 16-gauge needle to transfer the microdomes from the harvester to the wound; however, it was found with this dressing that the wounds appeared too moist and macerated when the bolster was removed at 1 week. A nonadhering silicone transfer dressing allowed better moisture control, was easier to use and remove, and was more permeable. It also performed well under a NPWT bolster. 

These study results have all the limitations of a retrospective case series, including patient and treatment selection biases, lack of a control group, and potential inaccuracies in medical records data. Larger, controlled studies are needed to quantify the effects of epidermal grafting and to determine the types of wounds that would most benefit from the procedure, as well as examine the efficacy of epidermal grafting as compared to allografts and other biologic alternatives.

Epidermal grafting played an integral role in the wound healing strategy for patients in this series with refractory open wounds. The new epidermal grafting technique provided a safe, simplified grafting option with low donor-site morbidity; it presented a viable alternative to surgery in outpatient clinics and wound centers for patients who were high-risk for surgery secondary to medical comorbidities and coagulopathies. This study supports other study observations to date of little to no pain and no complications with the harvesting procedure. Epidermal skin grafts offer an alternative to STSG, allografts, and other biologic dressings when only the epidermal layer is needed to treat a chronic, recalcitrant wound.

The author thanks Karen Beach (Acelity) for her editorial assistance in preparing this manuscript.

Affiliation: Alon Aesthetics Plastic Surgery, San Antonio, TX

Correspondence:
Regina M. Fearmonti, MD
Alon Aesthetics Plastic Surgery
San Antonio, TX
FearmontiPlasticSurgery@gmail.com 

Disclosure: The author is a consultant for KCI, an Acelity company, but received no financial assistance for this study.