Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene

L. Yao, W. Daly, B. Newland, S. Yao, W. Wang, B. K K Chen, N. Madigan, Anthony John Windebank, A. Pandit

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Functionalized biomaterial scaffolds targeted at improving axonal regeneration by enhancing guided axonal growth provide a promising approach for the repair of spinal cord injury. Collagen neural conduits provide structural guidance for neural tissue regeneration, and in this study it is shown that these conduits can also act as a reservoir for sustained gene delivery. Either a G-luciferase marker gene or a neurotrophin-3-encoding gene, complexed to a non-viral, cyclized, PEGylated transfection vector, was loaded within a multichannel collagen conduit. The complexed genes were then released in a controlled fashion using a dual release system both in vitro and in vivo. For evaluation of their biological performance, the loaded conduits were implanted into the completely transected rat thoracic spinal cord (T8-T10). Aligned axon regeneration through the channels of conduits was observed one month post-surgery. The conduits delivering neurotrophin-3 polyplexes resulted in significantly increased neurotrophin-3 levels in the surrounding tissue and a statistically higher number of regenerated axons versus the control conduits (P<0.05). This study suggests that collagen neural conduits delivering a highly effective non-viral therapeutic gene may hold promise for repair of the injured spinal cord.

Original languageEnglish (US)
Pages (from-to)1149-1157
Number of pages9
JournalGene Therapy
Volume20
Issue number12
DOIs
StatePublished - Dec 2013

Fingerprint

Spinal Cord Regeneration
Neurotrophin 3
Collagen
Regeneration
Genes
Axons
Biocompatible Materials
Luciferases
Spinal Cord Injuries
Transfection
Spinal Cord
Thorax
Growth

Keywords

  • 2-(Dimethylamino)ethyl methacrylate
  • neural conduits
  • non-viral gene delivery
  • spinal cord injury

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene. / Yao, L.; Daly, W.; Newland, B.; Yao, S.; Wang, W.; Chen, B. K K; Madigan, N.; Windebank, Anthony John; Pandit, A.

In: Gene Therapy, Vol. 20, No. 12, 12.2013, p. 1149-1157.

Research output: Contribution to journalArticle

Yao, L. ; Daly, W. ; Newland, B. ; Yao, S. ; Wang, W. ; Chen, B. K K ; Madigan, N. ; Windebank, Anthony John ; Pandit, A. / Improved axonal regeneration of transected spinal cord mediated by multichannel collagen conduits functionalized with neurotrophin-3 gene. In: Gene Therapy. 2013 ; Vol. 20, No. 12. pp. 1149-1157.
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