Sustained release of neurotrophin-3 via calcium phosphate-coated sutures promotes axonal regeneration after spinal cord injury

J Neurosci Res. 2016 Jul;94(7):645-52. doi: 10.1002/jnr.23730. Epub 2016 Mar 26.

Abstract

Because of the dynamics of spinal cord injury (SCI), the optimal treatment will almost certainly be a combination approach to control the environment and promote axonal growth. This study uses peripheral nerve grafts (PNGs) as scaffolds for axonal growth while delivering neurotrophin-3 (NT-3) via calcium phosphate (CaP) coatings on surgical sutures. CaP coating was grown on sutures, and NT-3 binding and release were characterized in vitro. Then, the NT-3-loaded sutures were tested in a complete SCI model. Rats were analyzed for functional improvement and axonal growth into the grafts. The CaP-coated sutures exhibited a burst release of NT-3, followed by a sustained release for at least 20 days. Functionally, the rats with PNGs + NT-3-loaded sutures and the rats treated with PNGs scored significantly higher than controls on day 56 postoperatively. However, functional scores in rats treated with PNGs + NT-3-loaded suture were not significantly different from those of rats treated with PNGs alone. Cholera toxin subunit B (CTB) labeling rostral to the graft was not observed in any controls, but CTB labeling rostral to the graft was observed in almost all rats that had had a PNG. Neurofilament labeling on transverse sections of the graft revealed that the rats treated with the NT-3-loaded sutures had significantly more axons per graft than rats treated with an NT-3 injection and rats without NT-3. These data demonstrate that PNGs serve as scaffolds for axonal growth after SCI and that CaP-coated sutures can efficiently release NT-3 to increase axonal regeneration. © 2016 Wiley Periodicals, Inc.

Keywords: RRID:AB_2532999; RRID:AB_2535788; RRID:AB_641021; calcium phosphate coating; neurotrophin-3; peripheral nerve grafts; regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects*
  • Calcium Phosphates / chemistry*
  • Cholera Toxin / pharmacology
  • Delayed-Action Preparations
  • Female
  • Graft Survival / drug effects
  • Nerve Regeneration / drug effects*
  • Neurofilament Proteins / metabolism
  • Neurotrophin 3 / administration & dosage*
  • Neurotrophin 3 / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / therapy*
  • Sutures*
  • Tissue Scaffolds

Substances

  • Calcium Phosphates
  • Delayed-Action Preparations
  • Neurofilament Proteins
  • Neurotrophin 3
  • Cholera Toxin