Neurotrophin-3 released from implant of tissue-engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury

J Biomed Mater Res A. 2018 Aug;106(8):2158-2170. doi: 10.1002/jbm.a.36414. Epub 2018 Apr 25.

Abstract

Spinal cord injury (SCI) normally results in cell death, scarring, cavitation, inhibitory molecules release, etc., which are regarded as a huge obstacle to reconnect the injured neuronal circuits because of the lack of effective stimulus. In this study, a functional gelatin sponge scaffold was used to inhibit local inflammation, enhance nerve fiber regeneration, and improve neural conduction in the canine. This scaffold had good porosity and modified with neurotrophin-3 (NT-3)/fibroin complex, which showed sustained release in vitro. After the scaffold was transplanted into canine spinal cord hemisection model, hindlimb movement, and neural conduction were improved evidently. Migrating host cells, newly formed neurons with associated synaptic structures together with functional blood vessels with intact endothelium in the regenerating tissue were identified. Taken together, the results demonstrated that using bioactive scaffold could establish effective microenvironment stimuli for endogenous regeneration, providing a potential and practical strategy for treatment of spinal cord injury. © 2018 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2158-2170, 2018.

Keywords: controlled artificial release system; inflammation; nerve fiber regeneration; neurotrophin-3; spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biocompatible Materials / pharmacology
  • Cell Movement / drug effects
  • Dogs
  • Evoked Potentials, Motor / drug effects
  • Female
  • Fibroins / pharmacology
  • Glial Fibrillary Acidic Protein / metabolism
  • Hindlimb / physiopathology
  • Inflammation / pathology*
  • Motor Activity* / drug effects
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology*
  • Nerve Regeneration* / drug effects
  • Neurotrophin 3 / pharmacology*
  • Prostheses and Implants
  • Spinal Cord / blood supply
  • Spinal Cord / drug effects
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology*
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry*

Substances

  • Biocompatible Materials
  • Glial Fibrillary Acidic Protein
  • Neurotrophin 3
  • Fibroins