A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers

Andrew Li, Akishige Hokugo, Anisa Yalom, Eric J. Berns, Nicholas Stephanopoulos, Mark T. McClendon, Luis A. Segovia, Igor Spigelman, Samuel I. Stupp, Reza Jarrahy

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Peripheral nerve injuries can result in lifelong disability. Primary coaptation is the treatment of choice when the gap between transected nerve ends is short. Long nerve gaps seen in more complex injuries often require autologous nerve grafts or nerve conduits implemented into the repair. Nerve grafts, however, cause morbidity and functional loss at donor sites, which are limited in number. Nerve conduits, in turn, lack an internal scaffold to support and guide axonal regeneration, resulting in decreased efficacy over longer nerve gap lengths. By comparison, peptide amphiphiles (PAs) are molecules that can self-assemble into nanofibers, which can be aligned to mimic the native architecture of peripheral nerve. As such, they represent a potential substrate for use in a bioengineered nerve graft substitute. To examine this, we cultured Schwann cells with bioactive PAs (RGDS-PA, IKVAV-PA) to determine their ability to attach to and proliferate within the biomaterial. Next, we devised a PA construct for use in a peripheral nerve critical sized defect model. Rat sciatic nerve defects were created and reconstructed with autologous nerve, PLGA conduits filled with various forms of aligned PAs, or left unrepaired. Motor and sensory recovery were determined and compared among groups. Our results demonstrate that Schwann cells are able to adhere to and proliferate in aligned PA gels, with greater efficacy in bioactive PAs compared to the backbone-PA alone. In vivo testing revealed recovery of motor and sensory function in animals treated with conduit/PA constructs comparable to animals treated with autologous nerve grafts. Functional recovery in conduit/PA and autologous graft groups was significantly faster than in animals treated with empty PLGA conduits. Histological examinations also demonstrated increased axonal and Schwann cell regeneration within the reconstructed nerve gap in animals treated with conduit/PA constructs. These results indicate that PA nanofibers may represent a promising biomaterial for use in bioengineered peripheral nerve repair.

Original languageEnglish
Pages (from-to)8780-8790
Number of pages11
JournalBiomaterials
Volume35
Issue number31
DOIs
Publication statusPublished - 2014

Fingerprint

Nanofibers
Amphiphiles
Peripheral Nerves
Peptides
Grafts
Schwann Cells
Transplants
Animals
Biocompatible Materials
isoleucyl-lysyl-valyl-alanyl-valine
Cells
Biomaterials
Recovery
Regeneration
arginyl-glycyl-aspartyl-serine
Repair
Peripheral Nerve Injuries
Aptitude
Defects
Recovery of Function

Keywords

  • Alignment
  • Nanofiber
  • Nerve conduit
  • Peptide amphiphile
  • Peripheral nerve repair
  • Self assembly

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Li, A., Hokugo, A., Yalom, A., Berns, E. J., Stephanopoulos, N., McClendon, M. T., ... Jarrahy, R. (2014). A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers. Biomaterials, 35(31), 8780-8790. https://doi.org/10.1016/j.biomaterials.2014.06.049

A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers. / Li, Andrew; Hokugo, Akishige; Yalom, Anisa; Berns, Eric J.; Stephanopoulos, Nicholas; McClendon, Mark T.; Segovia, Luis A.; Spigelman, Igor; Stupp, Samuel I.; Jarrahy, Reza.

In: Biomaterials, Vol. 35, No. 31, 2014, p. 8780-8790.

Research output: Contribution to journalArticle

Li, A, Hokugo, A, Yalom, A, Berns, EJ, Stephanopoulos, N, McClendon, MT, Segovia, LA, Spigelman, I, Stupp, SI & Jarrahy, R 2014, 'A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers', Biomaterials, vol. 35, no. 31, pp. 8780-8790. https://doi.org/10.1016/j.biomaterials.2014.06.049
Li A, Hokugo A, Yalom A, Berns EJ, Stephanopoulos N, McClendon MT et al. A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers. Biomaterials. 2014;35(31):8780-8790. https://doi.org/10.1016/j.biomaterials.2014.06.049
Li, Andrew ; Hokugo, Akishige ; Yalom, Anisa ; Berns, Eric J. ; Stephanopoulos, Nicholas ; McClendon, Mark T. ; Segovia, Luis A. ; Spigelman, Igor ; Stupp, Samuel I. ; Jarrahy, Reza. / A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers. In: Biomaterials. 2014 ; Vol. 35, No. 31. pp. 8780-8790.
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