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      Tailoring the Interface of Biomaterials to Design Effective Scaffolds

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          Abstract

          Tissue engineering (TE) is a multidisciplinary science, which including principles from material science, biology and medicine aims to develop biological substitutes to restore damaged tissues and organs. A major challenge in TE is the choice of suitable biomaterial to fabricate a scaffold that mimics native extracellular matrix guiding resident stem cells to regenerate the functional tissue. Ideally, the biomaterial should be tailored in order that the final scaffold would be (i) biodegradable to be gradually replaced by regenerating new tissue, (ii) mechanically similar to the tissue to regenerate, (iii) porous to allow cell growth as nutrient, oxygen and waste transport and (iv) bioactive to promote cell adhesion and differentiation. With this perspective, this review discusses the options and challenges facing biomaterial selection when a scaffold has to be designed. We highlight the possibilities in the final mold the materials should assume and the most effective techniques for its fabrication depending on the target tissue, including the alternatives to ameliorate its bioactivity. Furthermore, particular attention has been given to the influence that all these aspects have on resident cells considering the frontiers of materiobiology. In addition, a focus on chitosan as a versatile biomaterial for TE scaffold fabrication has been done, highlighting its latest advances in the literature on bone, skin, cartilage and cornea TE.

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          RGD and other recognition sequences for integrins.

          Proteins that contain the Arg-Gly-Asp (RGD) attachment site, together with the integrins that serve as receptors for them, constitute a major recognition system for cell adhesion. The RGD sequence is the cell attachment site of a large number of adhesive extracellular matrix, blood, and cell surface proteins, and nearly half of the over 20 known integrins recognize this sequence in their adhesion protein ligands. Some other integrins bind to related sequences in their ligands. The integrin-binding activity of adhesion proteins can be reproduced by short synthetic peptides containing the RGD sequence. Such peptides promote cell adhesion when insolubilized onto a surface, and inhibit it when presented to cells in solution. Reagents that bind selectively to only one or a few of the RGD-directed integrins can be designed by cyclizing peptides with selected sequences around the RGD and by synthesizing RGD mimics. As the integrin-mediated cell attachment influences and regulates cell migration, growth, differentiation, and apoptosis, the RGD peptides and mimics can be used to probe integrin functions in various biological systems. Drug design based on the RGD structure may provide new treatments for diseases such as thrombosis, osteoporosis, and cancer.
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            Vascular-specific growth factors and blood vessel formation.

            A recent explosion in newly discovered vascular growth factors has coincided with exploitation of powerful new genetic approaches for studying vascular development. An emerging rule is that all of these factors must be used in perfect harmony to form functional vessels. These new findings also demand re-evaluation of therapeutic efforts aimed at regulating blood vessel growth in ischaemia, cancer and other pathological settings.
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              Capturing complex 3D tissue physiology in vitro.

              The emergence of tissue engineering raises new possibilities for the study of complex physiological and pathophysiological processes in vitro. Many tools are now available to create 3D tissue models in vitro, but the blueprints for what to make have been slower to arrive. We discuss here some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment, and the methods for implementing them. We emphasize applications that involve epithelial tissues for which 3D models could explain mechanisms of disease or aid in drug development.
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                Author and article information

                Journal
                J Funct Biomater
                J Funct Biomater
                jfb
                Journal of Functional Biomaterials
                MDPI
                2079-4983
                21 August 2018
                September 2018
                : 9
                : 3
                : 50
                Affiliations
                [1 ]Centro Universitario di Odontoiatria, Università degli Studi di Parma, Via Gramsci 14, 43126 Parma, Italy; andrea.toffoli@ 123456unipr.it (A.T.); giulia.ghiacci@ 123456gmail.com (G.G.); guidomaria.macaluso@ 123456unipr.it (G.M.M.)
                [2 ]Dipartimento di Medicina e Chirurgia, Università degli Studi di Parma, Via Gramsci 14, 43126 Parma, Italy
                Author notes
                [* ]Correspondence: ludovica.parisi@ 123456unipr.it ; Tel.: +39-0521-906742
                Author information
                https://orcid.org/0000-0003-1641-7743
                https://orcid.org/0000-0003-2203-3092
                Article
                jfb-09-00050
                10.3390/jfb9030050
                6165026
                30134538
                e9d39a8d-123d-4803-bb9a-4a11ec81e436
                © 2018 by the authors.

                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
                : 08 August 2018
                : 17 August 2018
                Categories
                Review

                tissue engineering,biomaterials,chitosan
                tissue engineering, biomaterials, chitosan

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