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WIREs Nanomed Nanobiotechnol
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Tissue scaffolds for skin wound healing and dermal reconstruction

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Abstract One of the major applications of tissue‐engineered skin substitutes for wound healing is to promote the healing of cutaneous wounds. In this respect, many important clinical milestones have been reached in the past decades. However, currently available skin substitutes for wound healing often suffer from a range of problems including wound contraction, scar formation, and poor integration with host tissue. Engineering skin substitutes by tissue engineering approach has relied upon the creation of three‐dimensional scaffolds as extracellular matrix (ECM) analog to guide cell adhesion, growth, and differentiation to form skin‐functional and structural tissue. The three‐dimensional scaffolds can not only cover wound and give a physical barrier against external infection as wound dressing, but also can provide support both for dermal fibroblasts and the overlying keratinocytes for skin tissue engineering. A successful tissue scaffold should exhibit appropriate physical and mechanical characteristics and provide an appropriate surface chemistry and nano and microstructures to facilitate cellular attachment, proliferation, and differentiation. A variety of scaffolds have been fabricated based on materials ranging from naturally occurring ones to those manufactured synthetically. This review discusses a variety of commercial or laboratory‐engineered skin substitutes for wound healing. Central to the discussion are the scaffolds/materials, fabrication techniques, and their characteristics associated with wound healing. One specifically highlighted emerging fabrication technique is electrospinning that allows the design and fabrication of biomimetic scaffolds that offer tremendous potential applications in wound healing of skin. WIREs Nanomed Nanobiotechnol 2010 2 510–525 This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

Acellular skin substitutes: (A) appearance of Alloderm native tissue (Reprinted with permission from Ref 20. Copyright 2010 emedicine.com), (B) SEM micrograph of the surface (Reprinted with permission from Ref 24. Copyright 1981 Elsevier). (C) Integra® template with silicon layer in situ (Reprinted with permission from Ref 25. Copyright 2006 Elsevier). and (D) Porous sponge‐like collagen–glycosaminoglycans structure of Integra®. (Reprinted with permission from Ref 26. Copyright 2007 http://www.ilstraining.com/idrt/idrt/brs_it_03.html).

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Schematic illustration of layer‐by‐layer dermal reconstruction using nanofibrous scaffold. (Reprinted with permission from Ref 130. Copyright 2009 Mary Ann Liebert, Inc. Publishers).

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Electrospinning and electrospun nanofibers. (A) Schematic diagram of the electrospinning setup, (B) collagen nanofibers, (reprinted with permission from Ref 99. Copyright 2007 John Wiley & Sons, Inc.), scale bar = 100 nm, (C) PVA/AgNO3 nanofiber, (reprinted with permission from Ref 98. Copyright 2002 ACS), (D) core–shell polycaprolactone/ collagen nanofiber with the insert of the coaxial spinner, (reprinted with permission from Ref 100. Copyright 2005 ACS), and (E) polycaprolactone/gelatin nanofiber scaffold collected with Tegaderm™ membrane. (Reprinted with permission from Ref 101. Copyright 2007 Elsevier).

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Polyglactin mesh (A), Dermagraf® as received from a pack (B), dermal fibroblasts cultured on polyglactin mesh (C), and collagen‐hybridized polyglactin mesh (D), collagen promotes adhesion and growth of fibroblasts after 5 days of culture (A, C, D reprinted with permission from Ref 86. Copyright 2004 Expert Review of Medical Devices, and B reprinted with permission from Ref 86. Copyright 2004 Expert Review of Medical Devices).

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Optical microscopic photographs of collagen thread mesh (A), reinforced collagen sponge with collagen mesh (B), SEM micrographs of collagen sponge reinforced by collagen mesh (C), and the fibroblasts growing and filling the collagen mesh (D). (Reprinted with permission from Ref 54. Copyright 2008 Springer).

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Bilayered skin substitutes: (A) Apligraf® (Reprinted with permission from Ref 7. Copyright 2008 Elsevier). (B) Comparison of Apligraf® and natural human skin; Apligraf® exhibits similar structure as the natural skin. (Reprinted with permission from Ref 36. Apligraf®).

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