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      Tissue engineering of skin and regenerative medicine for wound care

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          Engineering of biologic skin substitutes has progressed over time from individual applications of skin cells, or biopolymer scaffolds, to combinations of cells and scaffolds for treatment, healing, and closure of acute and chronic skin wounds. Skin substitutes may be categorized into three groups: acellular scaffolds, temporary substitutes containing allogeneic skin cells, and permanent substitutes containing autologous skin cells. Combined use of acellular dermal substitutes with permanent skin substitutes containing autologous cells has been shown to provide definitive wound closure in burns involving greater than 90% of the total body surface area. These advances have contributed to reduced morbidity and mortality from both acute and chronic wounds but, to date, have failed to replace all of the structures and functions of the skin. Among the remaining deficiencies in cellular or biologic skin substitutes are hypopigmentation, absence of stable vascular and lymphatic networks, absence of hair follicles, sebaceous and sweat glands, and incomplete innervation. Correction of these deficiencies depends on regulation of biologic pathways of embryonic and fetal development to restore the full anatomy and physiology of uninjured skin. Elucidation and integration of developmental biology into future models of biologic skin substitutes promises to restore complete anatomy and physiology, and further reduce morbidity from skin wounds and scar. This article offers a review of recent advances in skin cell thrapies and discusses the future prospects in cutaneous regeneration.

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          CRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes.

          The CRISPR-Cas9 RNA-guided DNA endonuclease has contributed to an explosion of advances in the life sciences that have grown from the ability to edit genomes within living cells. In this Review, we summarize CRISPR-based technologies that enable mammalian genome editing and their various applications. We describe recent developments that extend the generality, DNA specificity, product selectivity, and fundamental capabilities of natural CRISPR systems, and we highlight some of the remarkable advancements in basic research, biotechnology, and therapeutics science that these developments have facilitated.
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            PPAR gamma gene--a review.

            Peroxisome proliferator-activated receptor gamma (PPARγ) has been the focus of intense research because ligands for this receptor have emerged as potent insulin sensitizers used in the treatment of type 2 diabetes. There have been described three PPAR isotypes α, δ and γ which have an integrated role in controlling the expression of genes playing key roles in the storage and mobilization of lipids, in glucose metabolism, in morphogenesis and inflammatory response. Recent advances include the discovery of novel genes that are regulated by PPARγ, which helps to explain how activation of this adipocyte predominant transcription factor regulates glucose and lipid homeostasis. Increased levels of circulating free fatty acids and lipid accumulation in non-adipose tissue have been implicated in the development of insulin resistance. This situation is improved by PPARγ ligands, which promotes fatty acid storage in fat deposits and regulates the expression of adipocyte-secreted hormones that impacts on glucose homeostasis. So the net result of the pleiotropic effects of PPARγ ligands is improvement of insulin sensitivity. This review highlights the roles that PPAR gamma play in the regulation of gene expression of multiple diseases including obesity, diabetes and cancer and highlights the gene isolation transformation role. Further studies are needed for the transformation of PPAR gamma gene in plants and evaluate in animals for the treatment of type 2 diabetes.
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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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                Author and article information

                Contributors
                +1-513-872-6080 , steven.boyce@uc.edu
                alalley@shrinent.org
                Journal
                Burns Trauma
                Burns Trauma
                Burns & Trauma
                BioMed Central (London )
                2321-3868
                2321-3876
                24 January 2018
                24 January 2018
                2018
                : 6
                : 4
                Affiliations
                [1 ]ISNI 0000 0001 2179 9593, GRID grid.24827.3b, Department of Surgery, , University of Cincinnati, ; P.O. Box 670558, Cincinnati, Ohio 45267-0558 USA
                [2 ]ISNI 0000 0004 0449 6752, GRID grid.415832.9, Research Department, , Shriners Hospitals for Children, ; Cincinnati, Ohio USA
                Author information
                http://orcid.org/0000-0002-7683-7646
                Article
                103
                10.1186/s41038-017-0103-y
                6040609
                30009192
                6219ea16-3575-4079-8fff-8a8713d4787e
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 18 September 2017
                : 12 December 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100011781, Shriners Hospitals for Children;
                Award ID: 85200
                Funded by: FundRef http://dx.doi.org/10.13039/100000005, U.S. Department of Defense;
                Award ID: W81XWH-13-2-0052
                Funded by: National Institutes of Health (US)
                Award ID: 1R21AR064341-01A1
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                burns,cell therapy,skin substitute,tissue engineering,wound closure,scar,regenerative medicine

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