• Open Access

A Fast pH-Switchable and Self-Healing Supramolecular Hydrogel Carrier for Guided, Local Catheter Injection in the Infarcted Myocardium

Authors

  • Maartje M. C. Bastings,

    1. Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
    2. Laboratory of Chemical Biology, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
    Current affiliation:
    1. These authors contributed equally to this work.
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  • Stefan Koudstaal,

    1. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, PO Box 85.500, 3508 GA Utrecht, The Netherlands
    2. Interuniversity Cardiology Institute of the Netherlands (ICIN), PO Box 19258, 3501 DG Utrecht, The Netherlands
    Current affiliation:
    1. These authors contributed equally to this work.
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  • Roxanne E. Kieltyka,

    1. Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
    2. Laboratory of Chemical Biology, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
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  • Yoko Nakano,

    1. Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
    2. Laboratory of Chemical Biology, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
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  • A. C. H. Pape,

    1. Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
    2. Laboratory of Chemical Biology, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
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  • Dries A. M. Feyen,

    1. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, PO Box 85.500, 3508 GA Utrecht, The Netherlands
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  • Frebus J. van Slochteren,

    1. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, PO Box 85.500, 3508 GA Utrecht, The Netherlands
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  • Pieter A. Doevendans,

    1. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, PO Box 85.500, 3508 GA Utrecht, The Netherlands
    2. Interuniversity Cardiology Institute of the Netherlands (ICIN), PO Box 19258, 3501 DG Utrecht, The Netherlands
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  • Joost P. G. Sluijter,

    1. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, PO Box 85.500, 3508 GA Utrecht, The Netherlands
    2. Interuniversity Cardiology Institute of the Netherlands (ICIN), PO Box 19258, 3501 DG Utrecht, The Netherlands
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  • E. W. Meijer,

    1. Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
    2. Laboratory of Chemical Biology, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
    3. Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
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  • Steven A. J. Chamuleau,

    Corresponding author
    1. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, PO Box 85.500, 3508 GA Utrecht, The Netherlands
    2. Interuniversity Cardiology Institute of the Netherlands (ICIN), PO Box 19258, 3501 DG Utrecht, The Netherlands
    • Steven A. J. Chamuleau, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, PO Box 85.500, 3508 GA Utrecht, The Netherlands.

      Patricia Y. W. Dankers, Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands

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  • Patricia Y. W. Dankers

    Corresponding author
    1. Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
    2. Laboratory of Chemical Biology, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands
    • Steven A. J. Chamuleau, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, PO Box 85.500, 3508 GA Utrecht, The Netherlands.

      Patricia Y. W. Dankers, Institute for Complex Molecular Systems, Eindhoven University of Technology, PO Box 513, 5600 MB Eindhoven, The Netherlands

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Abstract

Minimally invasive intervention strategies after myocardial infarction use state-of-the-art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH-switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1-m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self-healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model.

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