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      A Concise Review on Tissue Engineered Artificial Skin Grafts for Chronic Wound Treatment: Can We Reconstruct Functional Skin Tissue In Vitro?

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          Abstract

          Chronic wounds occur as a consequence of a prolonged inflammatory phase during the healing process, which precludes skin regeneration. Typical treatment for chronic wounds includes application of autografts, allografts collected from cadaver, and topical delivery of antioxidant, anti-inflammatory, and antibacterial agents. Nevertheless, the mentioned therapies are not sufficient for extensive or deep wounds. Moreover, application of allogeneic skin grafts carries high risk of rejection and treatment failure. Advanced therapies for chronic wounds involve application of bioengineered artificial skin substitutes to overcome graft rejection as well as topical delivery of mesenchymal stem cells to reduce inflammation and accelerate the healing process. This review focuses on the concept of skin tissue engineering, which is a modern approach to chronic wound treatment. The aim of the article is to summarize common therapies for chronic wounds and recent achievements in the development of bioengineered artificial skin constructs, including analysis of biomaterials and cells widely used for skin graft production. This review also presents attempts to reconstruct nerves, pigmentation, and skin appendages (hair follicles, sweat glands) using artificial skin grafts as well as recent trends in the engineering of biomaterials, aiming to produce nanocomposite skin substitutes (nanofilled polymer composites) with controlled antibacterial activity. Finally, the article describes the composition, advantages, and limitations of both newly developed and commercially available bioengineered skin substitutes.

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          Most cited references170

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          Design and fabrication of human skin by three-dimensional bioprinting.

          Three-dimensional (3D) bioprinting, a flexible automated on-demand platform for the free-form fabrication of complex living architectures, is a novel approach for the design and engineering of human organs and tissues. Here, we demonstrate the potential of 3D bioprinting for tissue engineering using human skin as a prototypical example. Keratinocytes and fibroblasts were used as constituent cells to represent the epidermis and dermis, and collagen was used to represent the dermal matrix of the skin. Preliminary studies were conducted to optimize printing parameters for maximum cell viability as well as for the optimization of cell densities in the epidermis and dermis to mimic physiologically relevant attributes of human skin. Printed 3D constructs were cultured in submerged media conditions followed by exposure of the epidermal layer to the air-liquid interface to promote maturation and stratification. Histology and immunofluorescence characterization demonstrated that 3D printed skin tissue was morphologically and biologically representative of in vivo human skin tissue. In comparison with traditional methods for skin engineering, 3D bioprinting offers several advantages in terms of shape- and form retention, flexibility, reproducibility, and high culture throughput. It has a broad range of applications in transdermal and topical formulation discovery, dermal toxicity studies, and in designing autologous grafts for wound healing. The proof-of-concept studies presented here can be further extended for enhancing the complexity of the skin model via the incorporation of secondary and adnexal structures or the inclusion of diseased cells to serve as a model for studying the pathophysiology of skin diseases.
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            Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects.

            Since its discovery approximately 200 years ago, chitosan, as a cationic natural polymer, has been widely used as a topical dressing in wound management owing to its hemostatic, stimulation of healing, antimicrobial, nontoxic, biocompatible and biodegradable properties. This article covers the antimicrobial and wound-healing effects of chitosan, as well as its derivatives and complexes, and its use as a vehicle to deliver biopharmaceuticals, antimicrobials and growth factors into tissue. Studies covering applications of chitosan in wounds and burns can be classified into in vitro, animal and clinical studies. Chitosan preparations are classified into native chitosan, chitosan formulations, complexes and derivatives with other substances. Chitosan can be used to prevent or treat wound and burn infections not only because of its intrinsic antimicrobial properties, but also by virtue of its ability to deliver extrinsic antimicrobial agents to wounds and burns. It can also be used as a slow-release drug-delivery vehicle for growth factors to improve wound healing. The large number of publications in this area suggests that chitosan will continue to be an important agent in the management of wounds and burns.
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              Advances in Skin Regeneration Using Tissue Engineering

              Tissue engineered skin substitutes for wound healing have evolved tremendously over the last couple of years. New advances have been made toward developing skin substitutes made up of artificial and natural materials. Engineered skin substitutes are developed from acellular materials or can be synthesized from autologous, allograft, xenogenic, or synthetic sources. Each of these engineered skin substitutes has their advantages and disadvantages. However, to this date, a complete functional skin substitute is not available, and research is continuing to develop a competent full thickness skin substitute product that can vascularize rapidly. There is also a need to redesign the currently available substitutes to make them user friendly, commercially affordable, and viable with longer shelf life. The present review focuses on providing an overview of advances in the field of tissue engineered skin substitute development, the availability of various types, and their application.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                06 July 2020
                July 2020
                : 9
                : 7
                : 1622
                Affiliations
                Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki 1 Street, 20-093 Lublin, Poland; agata.przekora@ 123456umlub.pl ; Tel.: +48-81-448-7026
                Author information
                https://orcid.org/0000-0002-6076-1309
                Article
                cells-09-01622
                10.3390/cells9071622
                7407512
                32640572
                a03370d1-91d7-494b-a0db-5064c0f59690
                © 2020 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 May 2020
                : 21 June 2020
                Categories
                Review

                biomaterials,skin substitutes,nanocomposites,antibacterial skin grafts,epidermal skin grafts,dermal skin grafts,dermo-epidermal skin grafts,mesenchymal stem cells,skin appendages

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