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Highly Elastic Micropatterned Hydrogel for Engineering Functional Cardiac Tissue

Authors

  • Nasim Annabi,

    1. Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
    2. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
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  • Kelly Tsang,

    1. Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
    2. Department of Materials Engineering, Monash University, Melbourne, Victoria, Australia
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  • Suzanne M. Mithieux,

    1. School of Molecular Bioscience, University of Sydney, Sydney, 2006, Australia
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  • Mehdi Nikkhah,

    1. Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
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  • Afshin Ameri,

    1. Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
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  • Ali Khademhosseini,

    Corresponding author
    1. Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
    2. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA
    • Ali Khademhosseini, Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA

      Anthony S. Weiss, School of Molecular Bioscience, University of Sydney, Sydney, 2006, Australia.

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  • Anthony S. Weiss

    Corresponding author
    1. School of Molecular Bioscience, University of Sydney, Sydney, 2006, Australia
    2. Charles Perkins Centre, University of Sydney, Sydney, 2006, Australia
    3. Bosch Institute, University of Sydney, Sydney, 2006, Australia
    • Ali Khademhosseini, Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139 USA

      Anthony S. Weiss, School of Molecular Bioscience, University of Sydney, Sydney, 2006, Australia.

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Abstract

Heart failure is a major international health issue. Myocardial mass loss and lack of contractility are precursors to heart failure. Surgical demand for effective myocardial repair is tempered by a paucity of appropriate biological materials. These materials should conveniently replicate natural human tissue components, convey persistent elasticity, promote cell attachment, growth and conformability to direct cell orientation and functional performance. Here, microfabrication techniques are applied to recombinant human tropoelastin, the resilience-imparting protein found in all elastic human tissues, to generate photocrosslinked biological materials containing well-defined micropatterns. These highly elastic substrates are then used to engineer biomimetic cardiac tissue constructs. The micropatterned hydrogels, produced through photocrosslinking of methacrylated tropoelastin (MeTro), promote the attachment, spreading, alignment, function, and intercellular communication of cardiomyocytes by providing an elastic mechanical support that mimics their dynamic mechanical properties in vivo. The fabricated MeTro hydrogels also support the synchronous beating of cardiomyocytes in response to electrical field stimulation. These novel engineered micropatterned elastic gels are designed to be amenable to 3D modular assembly and establish a versatile, adaptable foundation for the modeling and regeneration of functional cardiac tissue with potential for application to other elastic tissues.

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