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      Dermal Matrices and Bioengineered Skin Substitutes: A Critical Review of Current Options

      research-article

      , MD , *†‡ , , MD, PhD, FCCP †‡ , , MRepSci, PhD *§¶ , , MDBS, FRACS *§¶

      Plastic and Reconstructive Surgery Global Open

      Wolters Kluwer Health

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          Abstract

          Background:

          Over recent decades, scientists and surgeons have collaborated to develop various bioengineered and synthetic products as an alternative to skin grafts. Despite the numerous articles and reviews written about dermal skin substitutes, there is no general consensus.

          Methods:

          This article reviews dermal skin scaffolds used in clinical applications and experimental settings. For scaffold evaluation, we focused on clinical and/or histological results, and conclusions are listed. Explanations for general trends were sought based on existing knowledge about tissue engineering principles and wound healing mechanisms.

          Results:

          Decellularized dermis seems to remain the best option with no other acellular scaffold being clinically proven to gain better results yet. In general, chemically cross-linked products were seen to be less effective in skin tissue engineering. Biocompatibility could be enhanced by preseeding substitutes with fibroblasts to allow some natural scaffold remodeling before product application.

          Conclusions:

          Skin substitutes are a useful tool in plastic and reconstructive surgery practices as an alternative to skin grafts. In the choice of substitute, the general plastic surgery principle of replacing like tissue with like tissue seems to be still standing, and products most resembling the natural dermal extracellular matrix should be preferred.

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          Most cited references 101

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          Biomedical applications of collagen.

          Collagen is regarded as one of the most useful biomaterials. The excellent biocompatibility and safety due to its biological characteristics, such as biodegradability and weak antigenecity, made collagen the primary resource in medical applications. The main applications of collagen as drug delivery systems are collagen shields in ophthalmology, sponges for burns/wounds, mini-pellets and tablets for protein delivery, gel formulation in combination with liposomes for sustained drug delivery, as controlling material for transdermal delivery, and nanoparticles for gene delivery and basic matrices for cell culture systems. It was also used for tissue engineering including skin replacement, bone substitutes, and artificial blood vessels and valves. This article reviews biomedical applications of collagen including the collagen film, which we have developed as a matrix system for evaluation of tissue calcification and for the embedding of a single cell suspension for tumorigenic study. The advantages and disadvantages of each system are also discussed.
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            Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering.

             L. Ma (2003)
            Porous scaffolds for skin tissue engineering were fabricated by freeze-drying the mixture of collagen and chitosan solutions. Glutaraldehyde (GA) was used to treat the scaffolds to improve their biostability. Confocal laser scanning microscopy observation confirmed the even distribution of these two constituent materials in the scaffold. The GA concentrations have a slight effect on the cross-section morphology and the swelling ratios of the cross-linked scaffolds. The collagenase digestion test proved that the presence of chitosan can obviously improve the biostability of the collagen/chitosan scaffold under the GA treatment, where chitosan might function as a cross-linking bridge. A detail investigation found that a steady increase of the biostability of the collagen/chitosan scaffold was achieved when GA concentration was lower than 0.1%, then was less influenced at a still higher GA concentration up to 0.25%. In vitro culture of human dermal fibroblasts proved that the GA-treated scaffold could retain the original good cytocompatibility of collagen to effectively accelerate cell infiltration and proliferation. In vivo animal tests further revealed that the scaffold could sufficiently support and accelerate the fibroblasts infiltration from the surrounding tissue. Immunohistochemistry analysis of the scaffold embedded for 28 days indicated that the biodegradation of the 0.25% GA-treated scaffold is a long-term process. All these results suggest that collagen/chitosan scaffold cross-linked by GA is a potential candidate for dermal equivalent with enhanced biostability and good biocompatibility.
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              A review of tissue-engineered skin bioconstructs available for skin reconstruction.

              Situations where normal autografts cannot be used to replace damaged skin often lead to a greater risk of mortality, prolonged hospital stay and increased expenditure for the National Health Service. There is a substantial need for tissue-engineered skin bioconstructs and research is active in this field. Significant progress has been made over the years in the development and clinical use of bioengineered components of the various skin layers. Off-the-shelf availability of such constructs, or production of sufficient quantities of biological materials to aid rapid wound closure, are often the only means to help patients with major skin loss. The aim of this review is to describe those materials already commercially available for clinical use as well as to give a short insight to those under development. It seeks to provide skin scientists/tissue engineers with the information required to not only develop in vitro models of skin, but to move closer to achieving the ultimate goal of an off-the-shelf, complete full-thickness skin replacement.
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                Author and article information

                Journal
                Plast Reconstr Surg Glob Open
                Plast Reconstr Surg Glob Open
                GOX
                Plastic and Reconstructive Surgery Global Open
                Wolters Kluwer Health
                2169-7574
                January 2015
                06 February 2015
                : 3
                : 1
                Affiliations
                From the [* ]O’Brien Institute Melbourne, Fitzroy, VIC, Australia; []Free University Brussels (VUB), Brussels, Belgium; []Department of Plastic and Reconstructive Surgery, University Hospital of Brussels (UZ Brussel), Brussels, Belgium; [§ ]Faculty of Health Sciences, Australian Catholic University, Fitzroy, VIC, Australia; and []Melbourne University Department of Surgery, St. Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia.
                Author notes
                Heidi Debels, MD, Department of Plastic and Reconstructive Surgery, University Hospital Brussels (UZ Brussel), Laarbeeklaan 101, 1090 Brussel, Belgium, E-mail: heidi.debels@ 123456vub.ac.be
                Article
                00008
                10.1097/GOX.0000000000000219
                4323388
                Copyright © 2015 The Authors. Published by Lippincott Williams & Wilkins on behalf of The American Society of Plastic Surgeons. PRS Global Open is a publication of the American Society of Plastic Surgeons.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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