Neurite outgrowth in fibrin gels is regulated by substrate stiffness

Alan J. Man, Hillary E. Davis, Aki Itoh, Jonathan K Leach, Peter Bannerman

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Fibrin is a promising matrix for use in promoting nerve repair given its natural occurrence in peripheral nerve injuries, and the biophysical properties of this matrix can be regulated to modulate tissue regeneration. In this study, we examined the effect of physical and mechanical properties of fibrin gels on dorsal root ganglia (DRG) neurite extension. Increases in fibrinogen concentration increased the number of fibrin strands, resulting in decreased pore size and increased stiffness. Neurite extension was reduced when DRG explants were cultured within fibrin gels of increasing fibrinogen concentrations (from 9.5 to 141mg/mL). The addition of NaCl also increased the number of fibrin strands, reducing fiber diameter and porosity, while increasing mechanical strength, and reductions in neurite extension correlated with increases in NaCl content. We determined that neurite extension within fibrin gels is dependent on fibrinolysis and is mediated by the secretion of serine proteases and matrix metalloproteinases by entrapped DRGs, as confirmed by culturing cells in the presence of inhibitors against these enzymes and real-time-polymerase chain reaction. Taken together, the results of this study provide new insight into the effect of fibrin gel biophysical properties on neurite extension and suggest new opportunities to improve the efficacy of these materials when used as nerve guidance conduits.

Original languageEnglish (US)
Pages (from-to)2931-2942
Number of pages12
JournalTissue Engineering - Part A
Volume17
Issue number23-24
DOIs
StatePublished - Dec 1 2011

Fingerprint

Fibrin
Gels
Neurites
Stiffness
Substrates
Tissue regeneration
Spinal Ganglia
Polymerase chain reaction
Fibrinogen
Pore size
Strength of materials
Repair
Enzymes
Physical properties
Porosity
Peripheral Nerve Injuries
Diagnosis-Related Groups
Mechanical properties
Serine Proteases
Enzyme Inhibitors

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials
  • Medicine(all)

Cite this

Man, A. J., Davis, H. E., Itoh, A., Leach, J. K., & Bannerman, P. (2011). Neurite outgrowth in fibrin gels is regulated by substrate stiffness. Tissue Engineering - Part A, 17(23-24), 2931-2942. https://doi.org/10.1089/ten.tea.2011.0030

Neurite outgrowth in fibrin gels is regulated by substrate stiffness. / Man, Alan J.; Davis, Hillary E.; Itoh, Aki; Leach, Jonathan K; Bannerman, Peter.

In: Tissue Engineering - Part A, Vol. 17, No. 23-24, 01.12.2011, p. 2931-2942.

Research output: Contribution to journalArticle

Man, AJ, Davis, HE, Itoh, A, Leach, JK & Bannerman, P 2011, 'Neurite outgrowth in fibrin gels is regulated by substrate stiffness', Tissue Engineering - Part A, vol. 17, no. 23-24, pp. 2931-2942. https://doi.org/10.1089/ten.tea.2011.0030
Man, Alan J. ; Davis, Hillary E. ; Itoh, Aki ; Leach, Jonathan K ; Bannerman, Peter. / Neurite outgrowth in fibrin gels is regulated by substrate stiffness. In: Tissue Engineering - Part A. 2011 ; Vol. 17, No. 23-24. pp. 2931-2942.
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