Peripheral nerve regeneration using novel bioengineered peptide amphiphile nanofibers: In Vivo studies
Reza Jarrahy, MD; Akishige Hokugo, DDS, PhD; Andrew Li, MD; Anisa Yalom, MD; Luis A. Segovia, MD
Department of Plastic and Reconstructive Surgery, REBAR Lab, University of California, Los Angeles, Los Angeles, CA
Background: Peripheral nerve injuries can result in lifelong disability. Primary nerve repair is used for short nerve defects. Though autologous nerve can bridge longer defects, the harvesting procedure creates donor site morbidity. Nerve conduits lack an aligned internal scaffold to support and guide axonal regeneration. A peptide amphiphiles (PA) can self-assemble into aligned nanofibers, and can potentially mimic the native internal architecture of peripheral nerve. A bioactive epitope, RGDS (Arg-Gly-Asp-Ser) can be incorporated into PA nanofibers and have been shown to promote neuronal cell adhesion, growth, and migration. We have reported the favorable ability of PA nanofibers to support the proliferation of Schwann cells, key components in peripheral nerve healing. In this study, we devised a PA construct for use in a peripheral nerve critical sized defect model.
Methods: Rat sciatic nerve defects were created and reconstructed with autologous nerve, Poly (lactide-co-glycolide acid) (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.
Results: 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.
Conclusion: These results indicate that PA nanofibers may represent a promising biomaterial for use in bioengineered peripheral nerve repair.
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