Immunoengineering nerve repair

Proc Natl Acad Sci U S A. 2017 Jun 27;114(26):E5077-E5084. doi: 10.1073/pnas.1705757114. Epub 2017 Jun 13.


Injuries to the peripheral nervous system are major sources of disability and often result in painful neuropathies or the impairment of muscle movement and/or normal sensations. For gaps smaller than 10 mm in rodents, nearly normal functional recovery can be achieved; for longer gaps, however, there are challenges that have remained insurmountable. The current clinical gold standard used to bridge long, nonhealing nerve gaps, the autologous nerve graft (autograft), has several drawbacks. Despite best efforts, engineering an alternative "nerve bridge" for peripheral nerve repair remains elusive; hence, there is a compelling need to design new approaches that match or exceed the performance of autografts across critically sized nerve gaps. Here an immunomodulatory approach to stimulating nerve repair in a nerve-guidance scaffold was used to explore the regenerative effect of reparative monocyte recruitment. Early modulation of the immune environment at the injury site via fractalkine delivery resulted in a dramatic increase in regeneration as evident from histological and electrophysiological analyses. This study suggests that biasing the infiltrating inflammatory/immune cellular milieu after injury toward a proregenerative population creates a permissive environment for repair. This approach is a shift from the current modes of clinical and laboratory methods for nerve repair, which potentially opens an alternative paradigm to stimulate endogenous peripheral nerve repair.

Keywords: fractalkine; immunomodulation; macrophage; monocyte; nerve repair.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autografts
  • Chemokine CX3CL1 / pharmacology
  • Nerve Regeneration / immunology*
  • Peripheral Nerve Injuries / immunology
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / therapy*
  • Rats
  • Sciatic Nerve / physiology*
  • Sciatic Nerve / transplantation
  • Tissue Engineering*
  • Tissue Scaffolds / chemistry*


  • Chemokine CX3CL1
  • Cx3cl1 protein, rat