Affinity-based release of glial-derived neurotrophic factor from fibrin matrices enhances sciatic nerve regeneration

Matthew D. Wood, Amy M. Moore, Daniel A. Hunter, Sami Tuffaha, Gregory H. Borschel, Susan E. Mackinnon, Shelly E. Sakiyama-Elbert

Research output: Contribution to journalArticlepeer-review

Abstract

Glial-derived neurotrophic factor (GDNF) promotes both sensory and motor neuron survival. The delivery of GDNF to the peripheral nervous system has been shown to enhance regeneration following injury. In this study, we evaluated the effect of affinity-based delivery of GDNF from a fibrin matrix in a nerve guidance conduit on nerve regeneration in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated which received GDNF or nerve growth factor (NGF) with the delivery system within the conduit, control groups excluding one or more components of the delivery system, and nerve isografts. Nerves were harvested 6 weeks after treatment for analysis by histomorphometry and electron microscopy. The use of the delivery system (DS) with either GDNF or NGF resulted in a higher frequency of nerve regeneration vs. control groups, as evidenced by a neural structure spanning the 13 mm gap. The GDNF DS and NGF DS groups were also similar to the nerve isograft group in measures of nerve fiber density, percent neural tissue and myelinated area measurements, but not in terms of total fiber counts. In addition, both groups contained a significantly greater percentage of larger diameter fibers, with GDNF DS having the largest in comparison to all groups, suggesting more mature neural content. The delivery of GDNF via the affinity-based delivery system can enhance peripheral nerve regeneration through a silicone conduit across a critical nerve gap and offers insight into potential future alternatives to the treatment of peripheral nerve injuries.

Original languageEnglish (US)
Pages (from-to)959-968
Number of pages10
JournalActa Biomaterialia
Volume5
Issue number4
DOIs
StatePublished - May 2009
Externally publishedYes

Keywords

  • Drug delivery
  • Growth factor
  • Nerve guidance conduit
  • Peripheral nerve graft
  • Tissue engineering

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Fingerprint Dive into the research topics of 'Affinity-based release of glial-derived neurotrophic factor from fibrin matrices enhances sciatic nerve regeneration'. Together they form a unique fingerprint.

Cite this