Multifunctionalized Electrospun Silk Fibers Promote Axon Regeneration in the Central Nervous System

Authors

  • Corinne R. Wittmer,

    1. Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA
    Current affiliation:
    1. C.R.W. and T.C. contributed equally to this work.
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  • Thomas Claudepierre,

    1. Department of Ophthalmology and Eye Hospital, Faculty of Medicine, University of Leipzig, Liebigstrasse 10-14, D-04103 Leipzig, Germany
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  • Michael Reber,

    1. CNRS UPR 3212, University of Strasbourg, Institute of Cellular and Integrative Neurosciences, 67084 Strasbourg Cedex, France
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  • Peter Wiedemann,

    1. Department of Ophthalmology and Eye Hospital, Faculty of Medicine, University of Leipzig, Liebigstrasse 10-14, D-04103 Leipzig, Germany
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  • Jonathan A. Garlick,

    1. Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA
    2. Division of Cancer Biology and Tissue Engineering, Department of Oral and Maxillofacial Pathology, Tufts University, School of Dental medicine, 55 Kneeland Street, Boston, MA 02111, USA
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  • David Kaplan,

    1. Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA
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  • Christophe Egles

    Corresponding author
    1. Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA
    2. Division of Cancer Biology and Tissue Engineering, Department of Oral and Maxillofacial Pathology, Tufts University, School of Dental medicine, 55 Kneeland Street, Boston, MA 02111, USA
    3. Université de Technologie de Compiègne CNRS UMR 6600: BioMécanique et BioIngénierie Centre de Recherche, BP 20529 Rue Personne de Roberval, 60205 Compiègne, France
    • Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
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Abstract

The repair of central nerves remains a major challenge in regenerative neurobiology. Regenerative guides possessing critical features such as cell adhesion, physical guiding and topical stimulation are needed. To generate such a guide, silk-protein materials are prepared using electrospinning. Silk is selected for this study due to its biocompatibility and its ability to be electrospun for the formation of aligned biofunctional nanofibers. The addition of brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) or both to the electrospun fibers enables enhanced function without impact to the structure or the surface morphology. Only a small fraction of the loaded growth factors is released over time, allowing the fibers to continue to provide these factors to cells for extended periods. The entrapped factors remain active and available to the cells, as rat retinal ganglion cells (RGCs) exhibit longer axonal growth when in contact with the biofunctionalized fibers. Compared with unfunctionalized fibers, the growth of neurites increases 2-fold on fibers containing BDNF, 2.5-fold on fibers containing CNTF and almost 3-fold on fibers containing both factors. The results demonstrate the potential of aligned and functionalized electrospun silk fibers to promote nerve growth in the central nervous system, underlying the great potential of complex biomaterials in neuroregenerative strategies following axotomy and nerve-crush traumas.

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