Silk Hydrogels as Soft Substrates for Neural Tissue Engineering

Authors

  • Amy M. Hopkins,

    1. Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
    2. Institute of Bioengineering, School of Life Sciences and Institute for Chemical Sciences and Engineering, School of Basic Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
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  • Laura De Laporte,

    1. Institute of Bioengineering, School of Life Sciences and Institute for Chemical Sciences and Engineering, School of Basic Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
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  • Federico Tortelli,

    1. Institute of Bioengineering, School of Life Sciences and Institute for Chemical Sciences and Engineering, School of Basic Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
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  • Elise Spedden,

    1. Department of Physics and Astronomy and Center for Nanoscopic Physics, Tufts University, Medford, MA 02155, USA
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  • Cristian Staii,

    1. Department of Physics and Astronomy and Center for Nanoscopic Physics, Tufts University, Medford, MA 02155, USA
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  • Timothy J. Atherton,

    1. Department of Physics and Astronomy and Center for Nanoscopic Physics, Tufts University, Medford, MA 02155, USA
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  • Jeffrey A. Hubbell,

    1. Institute of Bioengineering, School of Life Sciences and Institute for Chemical Sciences and Engineering, School of Basic Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
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  • David L. Kaplan

    Corresponding author
    1. Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA
    • Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.

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Abstract

There is great need for soft biomaterials that match the stiffness of human tissues for tissue engineering and regeneration. Hydrogels are frequently employed for extracellular matrix functionalization and to provide appropriate mechanical cues. It is challenging, however, to achieve structural integrity and retain bioactive molecules in hydrogels for complex tissue formation that may take months to develop. This work aims to investigate mechanical and biochemical characteristics of silk hydrogels for soft tissue engineering, specifically for the nervous system. The stiffness of 1 to 8% silk hydrogels, measured by atomic force microscopy, is 4 to 33 kPa. The structural integrity of silk gels is maintained throughout embryonic chick dorsal root ganglion (cDRG) explant culture over 4 days whereas fibrin and collagen gels decrease in mass over time. Neurite extension of cDRGs cultured on 2 and 4% silk hydrogels exhibit greater growth than softer or stiffer gels. Silk hydrogels release <5% of neurotrophin-3 (NT-3) over 2 weeks and 11-day old gels show maintenance of growth factor bioactivity. Finally, fibronectin- and NT-3-functionalized silk gels elicit increased axonal bundling suggesting their use in bridging nerve injuries. These results support silk hydrogels as soft and sustainable biomaterials for neural tissue engineering.

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