Incorporation of chitosan microspheres into collagen-chitosan scaffolds for the controlled release of nerve growth factor

PLoS One. 2014 Jul 1;9(7):e101300. doi: 10.1371/journal.pone.0101300. eCollection 2014.

Abstract

Background: Artifical nerve scaffold can be used as a promising alternative to autologous nerve grafts to enhance the repair of peripheral nerve defects. However, current nerve scaffolds lack efficient microstructure and neurotrophic support.

Methods: Microsphere-Scaffold composite was developed by incorporating chitosan microspheres loaded with nerve growth factor (NGF-CMSs) into collagen-chitosan scaffolds (CCH) with longitudinally oriented microchannels (NGF-CMSs/CCH). The morphological characterizations, in vitro release kinetics study, neurite outgrowth assay, and bioactivity assay were evaluated. After that, a 15-mm-long sciatic nerve gap in rats was bridged by the NGF-CMSs/CCH, CCH physically absorbed NGF (NGF/CCH), CCH or nerve autograft. 16 weeks after implantation, electrophysiology, fluoro-gold retrograde tracing, and nerve morphometry were performed.

Results: The NGF-CMSs were evenly distributed throughout the longitudinally oriented microchannels of the scaffold. The NGF-CMSs/CCH was capable of sustained release of bioactive NGF within 28 days as compared with others in vitro. In vivo animal study demonstrated that the outcomes of NGF-CMSs/CCH were better than those of NGF/CCH or CCH.

Conclusion: Our findings suggest that incorporation of NGF-CMSs into the CCH may be a promising tool in the repair of peripheral nerve defects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chitosan*
  • Collagen*
  • Delayed-Action Preparations / therapeutic use
  • Drug Liberation
  • Male
  • Microspheres*
  • Nerve Growth Factor / administration & dosage*
  • Rats
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / injuries*

Substances

  • Delayed-Action Preparations
  • Collagen
  • Chitosan
  • Nerve Growth Factor

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (No. 30770571 and No. 30973052) and the National Hi-Tech Research and Development Program of China (863 Program) (No. 2002AA216101). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.