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      In vitro and in vivo Biocompatibility of Alginate Dialdehyde/Gelatin Hydrogels with and without Nanoscaled Bioactive Glass for Bone Tissue Engineering Applications

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          Abstract

          In addition to good mechanical properties needed for three-dimensional tissue engineering, the combination of alginate dialdehyde, gelatin and nano-scaled bioactive glass (45S5) is supposed to combine excellent cellular adhesion, proliferation and differentiation properties, good biocompatibility and predictable degradation rates. The goal of this study was to evaluate the in vitro and in vivo biocompatibility as a first step on the way to its use as a scaffold in bone tissue engineering. In vitro evaluation showed good cell adherence and proliferation of bone marrow derived mesenchymal stem cells seeded on covalently crosslinked alginate dialdehyde-gelatin (ADA-GEL) hydrogel films with and without 0.1% nano-Bioglass ®(nBG). Lactate dehydrogenase (LDH)- and mitochondrial activity significantly increased in both ADA-GEL and ADA-GEL-nBG groups compared to alginate. However, addition of 0.1% nBG seemed to have slight cytotoxic effect compared to ADA-GEL. In vivo implantation did not produce a significant inflammatory reaction, and ongoing degradation could be seen after four weeks. Ongoing vascularization was detected after four weeks. The good biocompatibility encourages future studies using ADA-GEL and nBG for bone tissue engineering application.

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          Cell encapsulation in biodegradable hydrogels for tissue engineering applications.

          Encapsulating cells in biodegradable hydrogels offers numerous attractive features for tissue engineering, including ease of handling, a highly hydrated tissue-like environment for cell and tissue growth, and the ability to form in vivo. Many properties important to the design of a hydrogel scaffold, such as swelling, mechanical properties, degradation, and diffusion, are closely linked to the crosslinked structure of the hydrogel, which is controlled through a variety of different processing conditions. Degradation may be tuned by incorporating hydrolytically or enzymatically labile segments into the hydrogel or by using natural biopolymers that are susceptible to enzymatic degradation. Because cells are present during the gelation process, the number of suitable chemistries and formulations are limited. In this review, we describe important considerations for designing biodegradable hydrogels for cell encapsulation and highlight recent advances in material design and their applications in tissue engineering.
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            Bioactive Glass and Glass-Ceramic Scaffolds for Bone Tissue Engineering

            Traditionally, bioactive glasses have been used to fill and restore bone defects. More recently, this category of biomaterials has become an emerging research field for bone tissue engineering applications. Here, we review and discuss current knowledge on porous bone tissue engineering scaffolds on the basis of melt-derived bioactive silicate glass compositions and relevant composite structures. Starting with an excerpt on the history of bioactive glasses, as well as on fundamental requirements for bone tissue engineering scaffolds, a detailed overview on recent developments of bioactive glass and glass-ceramic scaffolds will be given, including a summary of common fabrication methods and a discussion on the microstructural-mechanical properties of scaffolds in relation to human bone (structure-property and structure-function relationship). In addition, ion release effects of bioactive glasses concerning osteogenic and angiogenic responses are addressed. Finally, areas of future research are highlighted in this review.
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              Alginate hydrogels as synthetic extracellular matrix materials.

              Alginate hydrogels are used extensively in cell encapsulation, cell transplantation, and tissue engineering applications. Alginates possess many favorable properties required in biomaterials, but are unable to specifically interact with mammalian cells. We have therefore covalently modified alginate polysaccharides with RGD-containing cell adhesion ligands utilizing aqueous carbodiimide chemistry. The chemistry has been optimized and quantified with reaction efficiencies reaching 80% or greater. The concentration of peptide available for reaction was then varied to create hydrogels with a range of ligand densities. Mouse skeletal myoblasts were cultured on alginate hydrogel surfaces coupled with GRGDY peptides to illustrate achievement of cellular interaction with the otherwise non-adhesive hydrogel substrate. Myoblasts adhere to GRGDY-modified alginate surfaces, proliferate, fuse into multinucleated myofibrils, and express heavy-chain myosin which is a differentiation marker for skeletal muscle. Myoblast adhesion and spreading on these GRGDY-modified hydrogels was inhibited with soluble ligand added to the seeding medium, illustrating the specificity of adhesion to these materials. Alginate may prove to be an ideal material with which to confer specific cellular interactive properties, potentially allowing for the control of long-term gene expression of cells within these matrices.
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                Author and article information

                Journal
                Materials (Basel)
                Materials (Basel)
                Materials
                Materials
                MDPI
                1996-1944
                March 2014
                06 March 2014
                : 7
                : 3
                : 1957-1974
                Affiliations
                [1 ]Department of Plastic and Hand Surgery, University Hospital of Erlangen, Friedrich Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany; E-Mails: Ulrike.Rottensteiner@ 123456uk-erlangen.de (U.R.); diana-dafinova@ 123456hotmail.de (D.D.); subharath@ 123456iith.ac.in (S.N.R.); Justus.Beier@ 123456uk-erlangen.de (J.P.B.); ulrich.kneser@ 123456bgu-ludwigshafen.de (U.K.); Raymund.Horch@ 123456uk-erlangen.de (R.E.H.)
                [2 ]Institute of Biomaterials, Department of Materials Science and Engineering, Friedrich Alexander University Erlangen-Nuremberg, 91058 Erlangen, Germany; E-Mails: bapi.sarker@ 123456ww.uni-erlangen.de (B.S.); domiheusinger@ 123456web.de (D.H.); rainer.detsch@ 123456ww.uni-erlangen.de (R.D.)
                [3 ]Department of Hand, Plastic and Reconstructive Surgery-Burns Centre, BG Trauma Centre Ludwigshafen and Department of Plastic Surgery, University of Heidelberg, 67071 Ludwigshafen, Germany
                [4 ]Department of Biomedical Engineering, Indian Institute of Technology, Hyderabad 502205, India
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Authors to whom correspondence should be addressed; E-Mails: andreas.arkudas@ 123456uk-erlangen.de (A.A.); aldo.boccaccini@ 123456ww.uni-erlangen.de (A.R.B.); Tel.: +49-9131-85-33277 (A.A.); +49-9131-85-28601 (A.R.B.); Fax: +49-9131-85-39327 (A.A.); +49-9131-85-28602(A.R.B.).
                Article
                materials-07-01957
                10.3390/ma7031957
                5453292
                28788549
                120e4008-d470-4e2d-bf3c-aa8b4b9424c5
                © 2014 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 license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 23 December 2013
                : 09 February 2014
                : 26 February 2014
                Categories
                Article

                alginate dialdehyde,gelatin,nano-bioglass®,tissue engineering,biocompatibility,mesenchymal stem cells

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