Aligned neurite outgrowth and directed cell migration in self-assembled monodomain gels

Abstract Regeneration of neural tissues will require regrowth of axons lost due to trauma or degeneration to reestablish neuronal connectivity. One approach toward this goal is to provide directional cues to neurons that can promote and guide neurite growth. Our laboratory previously reported the fo...

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Bibliographic Details
Published inBiomaterials Vol. 35; no. 1; pp. 185 - 195
Main Authors Berns, Eric J, Sur, Shantanu, Pan, Liuliu, Goldberger, Joshua E, Suresh, Sunitha, Zhang, Shuming, Kessler, John A, Stupp, Samuel I
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.01.2014
Subjects
Advanced Basic Science
Alignment
Animals
Anisotropic gel
Cell Movement
Cells, Cultured
Dentistry
Gels
Mice
Microscopy, Electron, Scanning
Microscopy, Electron, Transmission
Nanofibers
Neurite growth
Neurites
Oligopeptides
Patch-Clamp Techniques
Peptide amphiphile
Self assembly
Synaptic Transmission
Tissue Scaffolds
Self assembly
Peptide amphiphile
Alignment
Neurite growth
Anisotropic gel
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Summary:Abstract Regeneration of neural tissues will require regrowth of axons lost due to trauma or degeneration to reestablish neuronal connectivity. One approach toward this goal is to provide directional cues to neurons that can promote and guide neurite growth. Our laboratory previously reported the formation of aligned monodomain gels of peptide amphiphile (PA) nanofibers over macroscopic length scales. In this work, we modified these aligned scaffolds specifically to support neural cell growth and function. This was achieved by displaying extracellular matrix (ECM) derived bioactive peptide epitopes on the surface of aligned nanofibers of the monodomain gel. Presentation of IKVAV or RGDS epitopes enhanced the growth of neurites from neurons encapsulated in the scaffold, while the alignment guided these neurites along the direction of the nanofibers. After two weeks of culture in the scaffold, neurons displayed spontaneous electrical activity and established synaptic connections. Scaffolds encapsulating neural progenitor cells were formed in situ within the spinal cord and resulted in the growth of oriented processes in vivo . Moreover, dorsal root ganglion (DRG) cells demonstrated extensive migration inside the scaffold, with the direction of their movement guided by fiber orientation. The bioactive and macroscopically aligned scaffold investigated here and similar variants can potentially be tailored for use in neural tissue regeneration.
Bibliography:These authors contributed equally to this work.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2013.09.077