About this item:

102 Views | 111 Downloads

Author Notes:

Corresponding Author: Ravi V. Bellamkonda Carol Ann and David D. Flanagan Chair in Biomedical Engineering Address: 3108 UA Whitaker Bldg, 313 Ferst Drive NE Atlanta, Georgia 30332-0535 Phone: 404.385.5038 Fax: 404-385-5044, ravi@gatech.edu

We would like to thank Dr. Balakrishna Pai, Dr. Tarun Saxena and Johnathan Lyon in the Bellamkonda Laboratory for helpful scientific and editorial discussions.

We would also like to thank Dr. Balakrishna Pai for generating the GFP-expressing RSC-96 Schwann cells used in the study.

Subjects:

Research Funding:

This work was supported by grants from the National Institutes of Health (NS44409, NS65109, 1R41NS06777-1).

Keywords:

  • Science & Technology
  • Technology
  • Engineering, Biomedical
  • Materials Science, Biomaterials
  • Engineering
  • Materials Science
  • Immunomodulation
  • Nerve regeneration
  • Macrophage
  • Cytokine
  • Scaffold
  • SPINAL-CORD-INJURY
  • RAT SCIATIC-NERVE
  • GROWTH-FACTOR
  • WALLERIAN DEGENERATION
  • SCHWANN-CELLS
  • HEMATOGENOUS MACROPHAGES
  • ENGINEERING STRATEGIES
  • GENE-EXPRESSION
  • SENSORY AXONS
  • STEM-CELLS

Effect of modulating macrophage phenotype on peripheral nerve repair

Tools:

Journal Title:

Biomaterials

Volume:

Volume 33, Number 34

Publisher:

, Pages 8793-8801

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Peripheral nerve repair across long gaps remains clinically challenging despite progress made with autograft transplantation. While scaffolds that present trophic factors and extracellular matrix molecules have been designed, matching the performance of autograft-induced repair has been challenging. In this study, we explored the effect of cytokine mediated 'biasing' of macrophage phenotypes on Schwann cell (SC) migration and axonal regeneration in vitro and in vivo. Macrophage phenotype was successfully modulated by local delivery of either Interferon-gamma (IFN-γ) or Interleukin-4 (IL-4) within polymeric nerve guidance channels, polarizing them toward pro-inflammatory (M1) or pro-healing (M2a and M2c) phenotypes, respectively. The initial polarization of macrophages to M2a and M2c phenotype results in enhanced SC infiltration and substantially faster axonal growth in a critically-sized rat sciatic nerve gap model (15 mm). The ratio of pro-healing to pro-inflammatory population of macrophages (CD206+/CCR7+), defined as regenerative bias, demonstrates a linear relationship with the number of axons at the distal end of the nerve scaffolds. The present results clearly suggest that rather than the extent of macrophage presence, their specific phenotype at the site of injury regulates the regenerative outcomes.

Copyright information:

© 2012 Elsevier Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Creative Commons License

Export to EndNote