Best‐practice algorithms for the use of a bilayered living cell therapy (Apligraf^®) in the treatment of lower‐extremity ulcers

Abstract

Tissue-engineered skin substitutes such as Apligraf have emerged over the past 20 years as among the most carefully studied and efficacious of the advanced wound modalities. These products have been proven as effective enhancements to general wound care, promoting wound closure particularly in instances where conventional wound care fails. Marketed for hard-to-heal wounds since 1998, Apligraf has become part of standard wound care in many wound centers across the United States. Despite this situation, few general wound care guidelines incorporate advanced and active wound-healing technologies, such as tissue-engineered skin products. Because of this deficiency, appropriate patient selection and proper use of these product remain largely unaddressed within the general wound care community. Here, we describe the development of guidelines surrounding optimal use of the bilayered living cell therapy, Apligraf, in the treatment of the two types of lower extremity ulcers for which the product is FDA approved: venous leg ulcer and diabetic foot ulcer. The guidelines detailed in this article focus on the identification and selection of patients who are at risk for failure of standard wound care therapy and thus appropriate for Apligraf treatment. The intended audience for these guidelines is the general wound care practitioner, for whom the developed treatment algorithms and accompanying figure legends should provide practical, user-friendly direction simplifying both patient selection and appropriate use of Apligraf within the context of good wound-healing practice.

Correction of Hypoxia, a Critical Element for Wound Bed Preparation Guidelines: TIMEO2 Principle of Wound Bed Preparation

“…[35][36][37][38] Originally, the technique was 29,30,53,55,56,69,76 developed for use in neonatology, 39 but it is now commonly used in pediatric intensive care units, 40 plastic surgery, 41 vascular surgery, 42 anesthesiology, 43 orthopedics, 44 and hyperbaric medicine. 45 Tissue oxygenation and perfusion data are collected to identify the presence of tissue hypoxia, responders to hyperoxia, and adequacy of perfusion. 35,46 Although several tests intended to identify significant wound hypoxia have been used, including ankle brachial index, skin perfusion pressure, and laser Doppler flow, transcutaneous oxygen is the most useful 43 for predicting the failure of a wound to heal, for predicting healing of planned amputation, for predicting response to HBO treatment, as well as for evaluating success of revascularization.…”

Scientific and industrial status of tissue engineering

“…Due to higher rate of chronic skin ulcers, the commercial value of the products that are licensed for treatment of this condition is higher than others (Jones et al, 2002). Therefore, various products are available for management of chronic skin ulcers including Apligraf (Organogenesis, USA) (Eaglstein and Falanga, 1997;Cavorsi et al, 2006;Curran and Plosker, 2002), Dermagraft (Smith and Nephew, UK and Advanced Tissue Sciences, USA) (Marston, 2004;Omar et al, 2004;Gentzkow et al, 1996), EpiDex (Euroderm, Germany) (Tausche et al, 2003), Epibase (Laboratoires Genévrier, France) (Vaillant, 2002;Soler, 2002), Myskin (CellTran, UK) (Moustafa et al, 2004), OrCel (Ortec, USA) (Still et al, 2003), BioSeed-S (BioTissue Technologies, Germany) (Johnsen et al, 2005), Hyalograft 3D, and Laserskin, (all by Fidia Advanced Biopolymers, Italy) (Caravaggi et al, 2003). The products that are marketed for cosmetic surgery applications include BioSeed-M (BioTissue Technologies AG, 2002) and MelanoSeed (both by BioTissue Technologies AG, Germany) (Westerhof et al, 2001).…”

Cost-Effectiveness of Three Adjunct Cellular/Tissue-Derived Products Used in the Management of Chronic Venous Leg Ulcers

“…In addition, the choice of bandage therapy (four-layer or short-stretch) did not materially affect healing times, recurrence rates, pain, or health-related quality of life. Because compression therapies offer only moderate benefit with recalcitrant VLUs, in recent years, alternative avenues have explored advanced therapeutics using cellular and/or tissue-derived products (CTPs) such as extracellular matrix (ECM; OASIS) [20], human skin equivalent (HSE; Apligraf) [21][22][23], and living skin equivalent (LSE; Dermagraft) [24][25][26][27]. Specifically, studies using CTPs focus on alleviating the stasis of wounds stuck in the inflammatory phase by supplying various biological factors, reducing levels of unwanted cytokines or enzymes (such as matrix metalloproteinases), and/or creating a temporary ECM (which results in granulation) [28].…”