Neurite extension and In vitro myelination within three-dimensional modified fibrin matrices

Régis Pittier, Fabrice Sauthier, Jeffrey A. Hubbell, Heike Hall

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

The deposition of fibrin clots in vivo occurs after injury in the peripheral nervous system and their removal correlates with nerve regeneration. Fibrin clots provide a provisional matrix for invading cells, induce wound healing, and become proteolytically removed by regenerating tissue. Here, neurite extension and in vitro myelination were studied within three-dimensional fibrin matrices that were covalently modified with the sixth Ig-like domain of cell adhesion molecules L1 containing N-terminal transglutaminase substrate sequences (TG-L1Ig6) for covalent incorporation into fibrin matrices. TG-L1Ig6 is a specific receptor for αvβ3-integrin involved in neurite extension of PC12 cells and dorsal root ganglion neurons (DRGs). Neurite extension of PC12 cells depended on interactions between cell surface αvβ3 and RGD-sites provided by TG-L1Ig6. In addition, matrix properties such as fibrin crosslink density and matrix degradation by serine proteases were crucial. No involvement of matrix metalloproteinases was found. DRG neurite extension in native fibrin matrices was retarded as compared to neurite extension within L1Ig6-modified and laminin-1-containing matrices. Moreover, myelinated structures were almost exclusively found in TG-L1Ig6-modified and laminin-1-containing matrices. These results indicate that potential use of three-dimensional matrices in a biomaterials-based healing device to induce and/or help in vivo nerve regeneration requires specific structural and biological signals.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalJournal of Neurobiology
Volume63
Issue number1
DOIs
StatePublished - Apr 1 2005

Keywords

  • αvβ3 integrin
  • Fibrin matrix
  • In vitro myelination
  • Nerve regeneration
  • Sixth Ig-like domain of cell adhesion molecule (L1Ig6)

ASJC Scopus subject areas

  • Neuroscience(all)

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