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      Gold Nanocomposite Bioink for Printing 3D Cardiac Constructs

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          Abstract

          <p class="first" id="P3">Bioprinting is the most convenient microfabrication method to create biomimetic three-dimensional (3D) cardiac tissue constructs, which can be used to regenerate damaged tissue and provide platforms for drug screening. However, existing bioinks, which are usually composed of polymeric biomaterials, are poorly conductive and delay efficient electrical coupling between adjacent cardiac cells. To solve this problem, we developed a gold nanorod (GNR) incorporated gelatin methacryloyl (GelMA)-based bioink for printing 3D functional cardiac tissue constructs. The GNR concentration was adjusted to create a proper microenvironment for the spreading and organization of cardiac cells. At optimized concentration of GNR, the nanocomposite bioink had a low viscosity, similar to pristine inks, which allowed for the easy integration of cells at high densities. As a result, rapid deposition of cell-laden fibers at a high resolution was possible, while reducing shear stress on the encapsulated cells. In the printed GNR constructs, cardiac cells showed improved cell adhesion and organization when compared to the constructs without GNRs. Furthermore, the incorporated GNRs bridged the electrically resistant pore walls of polymers, improved the cell-to-cell coupling, and promoted synchronized contraction of the bioprinted constructs. Given its advantageous properties, this gold nanocomposite bioink may find wide application in cardiac tissue engineering. </p><p id="P4"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/25779a35-a585-4008-8f86-59b496178418/PubMedCentral/image/nihms920195u1.jpg"/> </div> </p><p id="P5">We have developed a gold nanorod-incorporated gelatin methacryloyl-based bioink for printing of three-dimensional cardiac tissue constructs. The rapid deposition of the cell-laden fibers at a high resolution was achieved, while reducing the shear stress on the encapsulated cells. The incorporated gold nanorods improved the electrical propagation between cardiac cells and promoted their functional improvement in the printed cardiac construct. </p>

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          Most cited references23

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          Carbon-nanotube-embedded hydrogel sheets for engineering cardiac constructs and bioactuators.

          We engineered functional cardiac patches by seeding neonatal rat cardiomyocytes onto carbon nanotube (CNT)-incorporated photo-cross-linkable gelatin methacrylate (GelMA) hydrogels. The resulting cardiac constructs showed excellent mechanical integrity and advanced electrophysiological functions. Specifically, myocardial tissues cultured on 50 μm thick CNT-GelMA showed 3 times higher spontaneous synchronous beating rates and 85% lower excitation threshold, compared to those cultured on pristine GelMA hydrogels. Our results indicate that the electrically conductive and nanofibrous networks formed by CNTs within a porous gelatin framework are the key characteristics of CNT-GelMA leading to improved cardiac cell adhesion, organization, and cell-cell coupling. Centimeter-scale patches were released from glass substrates to form 3D biohybrid actuators, which showed controllable linear cyclic contraction/extension, pumping, and swimming actuations. In addition, we demonstrate for the first time that cardiac tissues cultured on CNT-GelMA resist damage by a model cardiac inhibitor as well as a cytotoxic compound. Therefore, incorporation of CNTs into gelatin, and potentially other biomaterials, could be useful in creating multifunctional cardiac scaffolds for both therapeutic purposes and in vitro studies. These hybrid materials could also be used for neuron and other muscle cells to create tissue constructs with improved organization, electroactivity, and mechanical integrity.
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            Controlling Shear Stress in 3D Bioprinting is a Key Factor to Balance Printing Resolution and Stem Cell Integrity.

            A microvalve-based bioprinting system for the manufacturing of high-resolution, multimaterial 3D-structures is reported. Applying a straightforward fluid-dynamics model, the shear stress at the nozzle site can precisely be controlled. Using this system, a broad study on how cell viability and proliferation potential are affected by different levels of shear stress is conducted. Complex, multimaterial 3D structures are printed with high resolution. This work pioneers the investigation of shear stress-induced cell damage in 3D bioprinting and might help to comprehend and improve the outcome of cell-printing studies in the future.
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              Surface chemistry and aspect ratio mediated cellular uptake of Au nanorods.

              Gold nanorods (Au NRs) have been recognized as promising materials for biomedical applications, like sensing, imaging, gene and drug delivery and therapy, but their toxicological issues are still controversial, especially for the Au NRs synthesized with seed-mediated method. In this study, we investigated the influence of aspect ratio and surface coating on their toxicity and cellular uptake. The cellular uptake is highly dependent on the aspect ratio and surface coating. However, the surface chemistry has the dominant roles since PDDAC-coated Au NRs exhibit a much greater ability to be internalized by the cells. The present data demonstrated shape-independent but coating-dependent cytotoxicity. Both the CTAB molecules left in the suspended solution and on the surface of Au NRs were identified as the actual cause of cytotoxicity. CTAB can enter cells with or without Au NRs, damage mitochondria, and then induce apoptosis. The effects of surface coating upon toxicity and cellular uptake were also examined using Au NRs with different coatings. When Au NRs were added into the medium, the proteins were quickly adsorbed onto the Au NRs that made the surface negatively charged. The surface charge may not directly affect the cellular uptake. We further demonstrated that the amount of serum proteins, especially for BSA, adsorbed on the Au NRs had a positive correlation with the capacity of Au NRs to enter cells. In addition, we have successfully revealed that the cationic PDDAC-coated Au NRs with an aspect ratio of 4 possess an ideal combination of both negligible toxicity and high cellular uptake efficiency, showing a great promise as photothermal therapeutic agents. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Advanced Functional Materials
                Adv. Funct. Mater.
                Wiley
                1616301X
                March 2017
                March 2017
                January 17 2017
                : 27
                : 12
                : 1605352
                Affiliations
                [1 ]Biomaterials Innovation Research Center; Department of Medicine; Brigham and Women's Hospital; Harvard Medical School; Cambridge MA 02139 USA
                [2 ]Harvard-MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology; Cambridge MA 02139 USA
                [3 ]Department of Cardiac Surgery; Zhongshan Hospital; Fudan University; Shanghai 200032 China
                [4 ]Wyss Institute for Biologically Inspired Engineering; Harvard University; Boston MA 02115 USA
                [5 ]Department of Developmental BioEngineering; University of Twente; Enschede Overijssel 7522 NB The Netherlands
                [6 ]Divisions of Genetics and Cardiovascular Medicine; Department of Medicine; Brigham and Women's Hospital; Harvard Medical School; Boston MA 02115 USA
                [7 ]Department of Electrical and Computer Engineering; King Abdulaziz University; Jeddah 21569 Saudi Arabia
                [8 ]Department of Bioindustrial Technologies; College of Animal Bioscience and Technology; Konkuk University; Seoul 143-701 Republic of Korea
                [9 ]Department of Physics; King Abdulaziz University; Jeddah 21569 Saudi Arabia
                Article
                10.1002/adfm.201605352
                6181228
                30319321
                4a5ae0ba-61b8-4f55-aebd-90f35753d1c9
                © 2017

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

                http://onlinelibrary.wiley.com/termsAndConditions

                http://onlinelibrary.wiley.com/termsAndConditions

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