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Skin Substitutes for Chronic Wounds

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Skin Substitutes for Chronic Wounds Resident CoRneR State-of-the-Art Wound Healing: Skin Substitutes for Chronic Wounds George Han, MD, PhD The care of chronic wounds represents an impor- not achieve adequate healing for chronic wounds, it tant and evolving area of dermatology. With a may be necessary to pursue other approaches. It has rising prevalence of chronic wounds bearing been estimated that chronic ulcers occur in up to notable effects on patient morbidity including 1.3% of the US adult population, mostly in the lower amputations, appropriate and effective inter- extremities.2,3 With the vast majority of amputations vention to treat these debilitating wounds can directly resulting from nonhealing ulcers in the legs,4 make a significant clinical impact. In recent appropriate and effective intervention can have a years, several advanced bioactive wound dress- substantial clinical impact. In recent years, numer- ings have been developedCUTIS to specifically treat ous advanced wound dressings have been developed chronic nonhealing wounds. These wound dress- specifically to treat chronic nonhealing wounds. ings encompass a wide range of products con- Because dermatologists will treat these patients, it is taining synthetic matrix scaffolds, animal-derived important for us to become familiar with these skin matrices, and human tissue. With several of these substitutes, which may become a more integral part wound dressings, randomized controlled trials of our armamentarium in caring for chronic wounds. (RCTs) have demonstrated improvement in wound Wound healing normally progresses through dis- healing;Do furthermore, cost-effectiveness Not studies tinct phases,Copy with the ultimate goal of reestablishing have suggested that these products may reduce barrier function and the structures normally found in the overall cost of treating a chronic wound. intact skin. Several mechanisms exist whereby wound Familiarity with these products and their appropri- healing does not progress, often due to underlying ate use may be helpful to dermatologists treating factors such as arteriovenous insufficiency, diabetes chronic wounds. mellitus, nutritional deficiency, infection, or physical Cutis. 2014;93:E13-E16. factors (ie, pressure ulcers). Some of these underlying conditions are straightforward to treat; for example, in the case of infection, antibiotics and active wound he care of chronic wounds is a challenging dressings containing silver, betaine, polyhexameth- topic and a growing area for clinical and ylene biguanide, or other antimicrobial substances research interest within dermatology. A review can help promote wound healing. However, many of T ® of wound care was presented in a Cutis resident cor- the other pathways to chronic wound physiology are ner column last year.1 When routine wound care does much more difficult to manage, with the underlying factor often being insufficient delivery of oxygen and nutrients to the wound.5 It is well known from the literature on burn wounds that a large nonhealing wound has direct effects on the body’s metabolism, From Albert Einstein College of Medicine/Montefiore Medical increasing the cardiac index and total body oxygen Center, New York, New York. The author reports no conflict of interest. consumption to levels comparable with other con- 6 Correspondence: George Han, MD, PhD ditions (eg, hyperthyroidism). As a result, kerati- ([email protected]). nocytes at the wound edge are no longer able to WWW.CUTIS.COM VOLUME 93, JANUARY 2014 E13 Copyright Cutis 2014. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Resident Corner successfully migrate centripetally to heal the wound and instead proliferate in place, forming a thick Skin Substitutes for Wound Healing hyperkeratotic layer that serves as the hallmark of a chronic wound edge.7 Synthetic skin substitutes have Wound Dressing Manufacturer been used to treat chronic wounds, not only forming Acellular Human Dermis a dressing to cover the ulcerated wound base but also actively participating in the wound healing process AlloDerm LifeCell Corporation with the addition of growth factors or cytokines that may directly stimulate angiogenesis or reepithelializa- AlloSkin AlloSource tion. In the early 1980s, the field of bioactive wound dressings started with cultured skin cells, which were DermACell Arthrex, Inc then applied to the wounds or tissue-engineered skin GammaGraft Promethean substitutes; this technology, which emerged from treating burn wounds when it was impractical or LifeSciences, Inc impossible to harvest enough graft tissue to treat the Graftjacket Kinetic Concepts, Inc burn, has evolved considerably since that time. This review will focus on tissue-engineered skin substi- Matrix HD RTI Surgical, Inc tutes and their application in the treatment of chro- nic wounds. TheraSkin Soluble Systems, LLC Synthetic Skin Substitutes Animal Derived A bioprosthetic skin substitute generally refers to a Biobranea Smith & Nephew, Inc material consisting of a biologically derived substance that may be combined with another material to allow Endoformb Hollister Wound for its application to a wound. There currently are Care LLC more than 50 skin substitutes on the market, with many more under development.CUTIS These skin substi- EZ Derma Mölnlycke Health Care tutes represent a biocompatible extracellular matrix template that allows for the migration of cells from Integraa Integra LifeSciences neighboring, ostensibly healthy tissue, encompassing Corporation either biomaterial (ie, noncellular matrices contain- b ing important proteins but no cellular components Oasis Wound Matrix Smith & Nephew, Inc derived from cadaveric, animal, or synthetic sources) PriMatrixb TEI Biosciences or cellularDo (ie, tissues harvested Not from human or ani- Copy mal origin) categories of products. However, there are TransCytea,c Smith & Nephew, Inc materials that contain components of each. Overall, these dressings are expensive to manufacture and Human Derived apply, which to some degree has prevented their Apligraf Organogenesis, Inc widespread adoption, but they remain useful and even cost effective in selected situations. Dermagraft Shire Regenerative Acellular Human Dermis—Acellular human der- Medicine, Inc mis products generally are derived from cadaveric skin tissue that has been treated with various deter- aUses a synthetic matrix coated with animal collagen gents, enzymes, and antibacterial and/or antimicro- or polypeptides. bUses an animal-derived extracellular matrix. bial agents to ensure that there is no immunogenicity cTransCyte also contains neonatal fibroblasts. or potential harm. These materials serve as biocom- patible scaffolds for cellular and vascular growth into the wound bed and allow for secondary tissue regeneration. Additionally, they can contain colla- gen, elastin, proteoglycans, and other proteins, which may in turn modulate the wound healing process. animal-derived extracellular matrix or a synthetic Examples of acellular human dermis wound dressings matrix coated with animal collagen or polypeptides, are provided in the Table. mostly porcine and/or bovine (Table). Both materi- Animal-Derived Matrix or Material—Several als aim to provide structural support in the form of a companies have taken the approach of using an matrix on which new tissue and vasculature can form E14 CUTIS® WWW.CUTIS.COM Copyright Cutis 2014. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Resident Corner while providing proteins and/or growth factors that extracellular matrix, which has been shown to sig- can modulate wound healing. nificantly (P.05) improve the proportion of wounds Human-Derived Products—Materials that incorpo- healed at 12 weeks in multiple studies.16-18 Some rate fibroblasts derived from human sources, generally other products have been tested in smaller trials, and from neonatal foreskin tissue, have been an inter- ongoing studies are being conducted. It has not been esting development in the field of skin substitutes. proven if these results can be extended to similar skin One such product, Dermagraft (Shire Regenerative substitutes, but the outlook is encouraging. Ideally, Medicine, Inc), also incorporates an extracellular further research will generate an environment in matrix and a bioabsorbable polyglactin mesh. The which several products are available and can compete major benefit is that the fibroblasts are able to directly on a cost-efficient basis to allow for more widespread generate growth factors, collagen, cytokines, and application of these novel skin substitutes. glycosaminoglycans to contribute to healing in the wound environment. This approach has proven quite Cost-effectiveness efficacious in treating wounds such as diabetic foot Numerous studies analyzing the cost of chronic ulcers8; however, a few theoretical yet unproven risks wound treatment with biosynthetic skin substitutes include rejection of and hypersensitivity to this mate- have been conducted. Given the substantial eco- rial due to trace amounts of bovine serum. nomic burden of chronic wounds in general, includ- The other major skin substitute in this class is ing costly inpatient admissions, skilled nursing for Apligraf (Organogenesis, Inc), an allogenic, cultured, dressing changes, and material costs, it is important bilayered skin equivalent. With this material, a der- to note that marked improvement in overall heal- mal layer
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