BACKGROUND

Normal healthy skin provides a protective barrier against microbes, water loss, and ultraviolet light damage; helps with thermoregulation; and provides tactile sensations. Wounds are disruptions of the skin’s structural and functional integrity and normally transition through distinct phases of healing until the skin’s structure and function are restored. Chronic wounds have failed to pass through the normal healing process. Patients with chronic wounds, such as diabetic foot ulcers and venous leg ulcers, experience loss of function, pain, wound recurrence, and significant morbidity. Care for chronic wounds involves removing necrotic tissue, applying dressings that maintain a moist wound environment, treating wound infections, and restoring blood flow to the wound site. If these procedures fail to restore the healing process, additional therapies may be considered.

PURPOSE

This Technical Brief describes the various products commercially available in the United States that may be considered skin substitutes, examines systems used to classify skin substitutes, identifies and assesses the clinical literature evaluating skin substitutes published since the 2012 AHRQ report , and suggests the best practices that may be part of any future studies evaluating skin substitutes.

METHODS

We performed a systematic search of the published literature (EMBASE, MEDLINE, PubMed, CINAHL) and grey literature since 2012. We received scientific packets from manufacturers during AHRQ’s call for Supplemental Evidence and Data for Systematic Reviews (SEADS) from March 25 to April 29, 2019. We searched for systematic reviews/meta-analyses, randomized controlled trials (RCTs), and prospective nonrandomized comparative studies examining commercially available skin substitutes in individuals with diabetic foot ulcers, venous leg ulcers, pressure ulcers, and arterial leg ulcers. We extracted data on clinical outcomes, such as complete wound healing, healing rate, and recurrence. We compared study eligibility criteria and outcomes measured between included studies and ongoing clinical trials registered in ClinicalTrials.gov to identify trends in the field. We interviewed Key Informants with expertise in chronic wound care to help identify classification systems to categorize the skin substitutes, guide study eligibility criteria, describe limitations in the current field, and recommend best practices for designing future studies.

FINDINGS

We identified 76 commercially available skin substitutes and categorized them based on the Davison-Kotler classification system. Sixty-eight (89%) were categorized as acellular dermal substitutes, mostly replacements from human placental membranes and animal tissue sources. Three systematic reviews and 22 RCTs examined use of 16 distinct skin substitutes, including acellular dermal substitutes, cellular dermal substitutes, and cellular epidermal and dermal substitutes in diabetic foot ulcers, pressure ulcers, and venous leg ulcers. Twenty-one ongoing clinical trials (all RCTs) examined an additional nine skin substitutes with similar classifications. Studies rarely reported clinical outcomes, such as amputation, wound recurrence at least 2 weeks after treatment ended, or patient-related outcomes, such as return to function, pain, exudate, and odor. The lack of studies examining the efficacy of most skin substitute products and the need for better-designed and -reported studies providing more clinically relevant data in this field are this Technical Brief’s clearest implications.