Introduction

Living skin equivalent (LSE)*, or tissue-engineered skin, is a bilaminar structure of epithelium cultured upon a dermal equivalent. Clinically, it has characteristics that closely resemble a skin graft. As such, it is used in the capacity of a prefabricated skin graft. LSE is currently approved by the FDA for chronic wounds, specifically certain diabetic foot ulcers (DFU) and venous stasis ulcers (VSU).1–3 As clinical experience broadens with LSE, physicians across the country are reporting its use in the treatment of other, “off-label” wounds beyond those approved by the FDA, such as acute excisional wounds4,5 (including Mohs surgery), epidermolysis bullosa,6 and other dermatologic conditions, such as ulcerative sarcoidosis,7 necrobiosis lipoidica,8 and pyoderma gangrenosum.9 Most of these reports have been case reports or small series. The authors have experienced a broadening of indications for LSE within their own practice and have found LSE particularly useful in avulsion injuries and certain salvage situations (those situations where an autologous graft or flap has experienced necrosis). However, learning how to properly select wounds for management with tissue engineered skin and learning proper post-application dressing management are processes acquired with time and experience.

Materials and Methods

The medical records of 58 patients treated with 84 separate LSE grafts were reviewed retrospectively. This represents a three-year experience with LSE (January 1999 through July 2001). Living skin equivalent is a bilaminar skin equivalent produced by seeding a type I bovine collagen matrix with human fibroblasts. Upon this, human keratinocytes are then cultured and allowed to stratify and cornify. The result is a bilayered living tissue with dermis and epithelial components. Of the 58 patients treated, 41 were treated for indications other than venous stasis disease or diabetic foot ulcer. These are “off-label” applications and make up the study population. Seventy-seven percent of our applications were for alternate applications; whereas, 23 percent were for VSU or DFU. The etiology of each wound treated is as follows (Figure 1):
• 30-percent traumatic
• 23-percent salvage
• 21-percent venous stasis ulcer (VSU)
• 8-percent burn
• 7-percent iatrogenic
• 5-percent pressure ulcer
• 4-percent other
• 2-percent diabetic foot ulcer (DFU).

The location of application within the alternate-use subset was as follows (Figure 2):
• 56-percent lower extremity
• 27-percent trunk
• 15-percent upper extremity
• 2-percent head and neck.

Within the alternate application group, the age range of patients was 19 years to 92 years. Of these patients, 54 percent had two or more significant systemic comorbidities. In fact, 22 percent were chronic systemic steroid users, 24 percent had diabetes, and 27 percent were active smokers. Eighty-six percent of these wounds had failed a physician-supervised, conservative regimen of wound care. The average wound age at the time of LSE treatment was 94 days.

Results

Seventy-eight percent of all wounds in the alternate application group healed completely. Twelve percent of wounds healed by at least 50 percent (partial wound healing) and ten percent exhibited minimal (< 50%) or no healing (Figure 3). No wounds were worse (larger or more painful), and no instances of wound infection occurred. Average time to complete healing was 8.9 weeks.

Discussion

The authors have found tissue-engineered skin to be an effective wound treatment for wounds in addition to those for which it carries FDA approval (diabetic foot ulcers and venous stasis ulcers). Small series of alternate uses have been published in the past, but no broad-range clinical experiences are currently available.