Electrophysiological assessment of a peptide amphiphile nanofiber nerve graft for facial nerve repair

Abstract

Facial nerve injury can cause severe long-term physical and psychological morbidity. There are limited repair options for an acutely transected facial nerve not amenable to primary neurorrhaphy. We hypothesize that a peptide amphiphile nanofiber neurograft may provide the nanostructure necessary to guide organized neural regeneration. Five experimental groups were compared, animals with (1) an intact nerve, (2) following resection of a nerve segment, and following resection and immediate repair with either a (3) autograft (using the resected nerve segment), (4) neurograft, or (5) empty conduit. The buccal branch of the rat facial nerve was directly stimulated with charge balanced biphasic electrical current pulses at different current amplitudes whereas nerve compound action potentials (nCAPs) and electromygraphic responses were recorded. After 8 weeks, the proximal buccal branch was surgically reexposed and electrically evoked nCAPs were recorded for groups 1-5. As expected, the intact nerves required significantly lower current amplitudes to evoke an nCAP than those repaired with the neurograft and autograft nerves. For other electrophysiologic parameters such as latency and maximum nCAP, there was no significant difference between the intact, autograft, and neurograft groups. The resected group had variable responses to electrical stimulation, and the empty tube group was electrically silent. Immunohistochemical analysis and transmission electron microscopy confirmed myelinated neural regeneration. This study demonstrates that the neuroregenerative capability of peptide amphiphile nanofiber neurografts is similar to the current clinical gold standard method of repair and holds potential as an off-the-shelf solution for facial reanimation and potentially peripheral nerve repair.

Sequence‐Optimized Peptide Nanofibers as Growth Stimulators for Regeneration of Peripheral Neurons

“…The reported animal studies used different parameters to assess functional regeneration such as histology, gene expression, and functional tests. For instance, nanofiber‐filled neurografts were comparable to the gold standard (i.e., a nerve autograft) in enhancing nerve action potential propagation after a facial nerve injury . In a different histological parameter, the nanofiber‐filled neurograft was even superior to the autograft and restored the axon diameter of injured axons almost completely to pre‐injury levels .…”

“…For instance, nanofiber‐filled neurografts were comparable to the gold standard (i.e., a nerve autograft) in enhancing nerve action potential propagation after a facial nerve injury . In a different histological parameter, the nanofiber‐filled neurograft was even superior to the autograft and restored the axon diameter of injured axons almost completely to pre‐injury levels . However, most available studies could only demonstrate a limited increase in individual regeneration parameters, which did not exceed effects observed with nerve autografts.…”

“…In contrast, there are only a few studies of PNFs in PNS regeneration. So far, two model systems of PNS regeneration, that is, facial or sciatic nerve regeneration, were mainly employed. For those studies, different PNFs were used including nanofibers composed of C16VVVAAAEEE or RADA 16‐I derived SAPs with two functional motifs IKVAV and RGD 16a,b.…”

“…So far, two model systems of PNS regeneration, that is, facial or sciatic nerve regeneration, were mainly employed. For those studies, different PNFs were used including nanofibers composed of C16VVVAAAEEE or RADA 16‐I derived SAPs with two functional motifs IKVAV and RGD 16a,b. These nanofibers were incorporated into collagen tubes, poly lactic‐co‐glycolic acid (PLGA) tubes,16b,c or hydrogels 16a.…”

“…For those studies, different PNFs were used including nanofibers composed of C16VVVAAAEEE or RADA 16‐I derived SAPs with two functional motifs IKVAV and RGD 16a,b. These nanofibers were incorporated into collagen tubes, poly lactic‐co‐glycolic acid (PLGA) tubes,16b,c or hydrogels 16a. This is one of the first studies applying “free” nanofibers without any filling into conduits.…”