Incorporation of heparin-binding peptides into fibrin gels enhances neurite extension: An example of designer matrices in tissue engineering

Shelly E. Sakiyama, Jason C. Schense, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

The goal of this work was to improve the potential of fibrin to promote nerve regeneration by enzymatically incorporating exogenous neurite-promoting heparin-binding peptides. The effects on neurite extension of four different heparin-binding peptides, derived from the heparin-binding domains of antithrombin III, neural cell adhesion molecule and platelet factor 4, were determined. These exogenous peptides were synthesized as bi-domain peptide chimeras, with the second domain being a substrate for factor XIIIa. This coagulation transglutaminase covalently bound the peptides within the fibrin gel during coagulation. The heparin-binding peptides enhanced the degree of neurite extension from embryonic chick dorsal root ganglia through 3- dimensional fibrin gels, and the extent of enhancement was found to correlate positively with the heparin-binding affinity of the individual domains. The enhancement could be inhibited by competition with soluble heparin, by degradation of cell-surface proteoglycans, and by inhibition of the covalent immobilization of the peptide. These results demonstrate an important potential role for proteoglycan-binding components of the extracellular matrix in neurite extension and suggest that fibrin gels modified with covalently bound heparin-binding peptides could serve as a therapeutic agent to enhance peripheral nerve regeneration through nerve guide tubes. More generally, the results demonstrate that the biological responses to fibrin, the body's natural wound healing matrix, can be dramatically improved by the addition of exogenous bioactive peptides in a manner such that they become immobilized during coagulation. - Sakiyama, S. E., Schense, J. C., Hubbell, J. A. Incorporation of heparin-binding peptides into fibrin gels enhances neurite extension: An example of designer matrices in tissue engineering.

Original languageEnglish
Pages (from-to)2214-2224
Number of pages11
JournalFASEB Journal
Volume13
Issue number15
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

tissue engineering
neurites
fibrin
heparin
Neurites
Tissue Engineering
Fibrin
Tissue engineering
Heparin
Gels
gels
peptides
Peptides
Coagulation
coagulation
Nerve Regeneration
Proteoglycans
proteoglycans
protein-glutamine gamma-glutamyltransferase
nerve tissue

Keywords

  • Antithrombin III
  • Neural cell adhesion molecule
  • Platelet factor 4
  • Regeneration

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Incorporation of heparin-binding peptides into fibrin gels enhances neurite extension : An example of designer matrices in tissue engineering. / Sakiyama, Shelly E.; Schense, Jason C.; Hubbell, Jeffrey A.

In: FASEB Journal, Vol. 13, No. 15, 01.01.1999, p. 2214-2224.

Research output: Contribution to journalArticle

Sakiyama, Shelly E. ; Schense, Jason C. ; Hubbell, Jeffrey A. / Incorporation of heparin-binding peptides into fibrin gels enhances neurite extension : An example of designer matrices in tissue engineering. In: FASEB Journal. 1999 ; Vol. 13, No. 15. pp. 2214-2224.
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