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      Protein/polysaccharide-based scaffolds mimicking native extracellular matrix for cardiac tissue engineering applications : Protein/Polysaccharide scaffolds for cardiac tissue engineering

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          Abstract

          <p class="first" id="P1">Tissue engineering has emerged as a viable approach to treat disease or repair damage in tissues and organs. One of the key elements for the success of tissue engineering is the use of a scaffold serving as artificial extracellular matrix (ECM). The ECM hosts the cells and improves their survival, proliferation, and differentiation, enabling the formation of new tissue. Here, we propose the development of a class of protein/polysaccharide-based porous scaffolds for use as ECM substitutes in cardiac tissue engineering. Scaffolds based on blends of a protein component, collagen or gelatin, with a polysaccharide component, alginate, were produced by freeze-drying and subsequent ionic and chemical crosslinking. Their morphological, physicochemical, and mechanical properties were determined and compared with those of natural porcine myocardium. We demonstrated that our scaffolds possessed highly porous and interconnected structures, and the chemical homogeneity of the natural ECM was well reproduced in both types of scaffolds. Furthermore, the alginate/gelatin (AG) scaffolds better mimicked the native tissue in terms of interactions between components and protein secondary structure, and in terms of swelling behavior. The AG scaffolds also showed superior mechanical properties for the desired application and supported better adhesion, growth, and differentiation of myoblasts under static conditions. The AG scaffolds were subsequently used for culturing neonatal rat cardiomyocytes, where high viability of the resulting cardiac constructs was observed under dynamic flow culture in a microfluidic bioreactor. We therefore propose our protein/polysaccharide scaffolds as a viable ECM substitute for applications in cardiac tissue engineering. </p>

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          Collagens—structure, function, and biosynthesis

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            A liver-on-a-chip platform with bioprinted hepatic spheroids.

            The inadequacy of animal models in correctly predicting drug and biothreat agent toxicity in humans has resulted in a pressing need for in vitro models that can recreate the in vivo scenario. One of the most important organs in the assessment of drug toxicity is liver. Here, we report the development of a liver-on-a-chip platform for long-term culture of three-dimensional (3D) human HepG2/C3A spheroids for drug toxicity assessment. The bioreactor design allowed for in situ monitoring of the culture environment by enabling direct access to the hepatic construct during the experiment without compromising the platform operation. The engineered bioreactor could be interfaced with a bioprinter to fabricate 3D hepatic constructs of spheroids encapsulated within photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. The engineered hepatic construct remained functional during the 30 days culture period as assessed by monitoring the secretion rates of albumin, alpha-1 antitrypsin, transferrin, and ceruloplasmin, as well as immunostaining for the hepatocyte markers, cytokeratin 18, MRP2 bile canalicular protein and tight junction protein ZO-1. Treatment with 15 mM acetaminophen induced a toxic response in the hepatic construct that was similar to published studies on animal and other in vitro models, thus providing a proof-of-concept demonstration of the utility of this liver-on-a-chip platform for toxicity assessment.
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              Exploring and engineering the cell surface interface.

              Cells are inherently sensitive to local mesoscale, microscale, and nanoscale patterns of chemistry and topography. We review current approaches to control cell behavior through the nanoscale engineering of materials surfaces. Far-reaching implications are emerging for applications including medical implants, cell supports, and materials that can be used as instructive three-dimensional environments for tissue regeneration.
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                Author and article information

                Journal
                Journal of Biomedical Materials Research Part A
                J. Biomed. Mater. Res.
                Wiley
                15493296
                March 2018
                March 2018
                November 20 2017
                : 106
                : 3
                : 769-781
                Affiliations
                [1 ]Department of Civil and Industrial Engineering; University of Pisa, Largo Lucio Lazzarino; Pisa 56126 Italy
                [2 ]Division of Engineering in Medicine, Department of Medicine; Brigham and Women's Hospital, Harvard Medical School; Boston Massachusetts 02139
                [3 ]Harvard-MIT Division of Health Sciences and Technology; Cambridge Massachusetts 02139
                Article
                10.1002/jbm.a.36272
                5845858
                29052369
                3e409117-9af7-4112-be4f-254f7d766127
                © 2017

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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