A neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel enhances rat sciatic nerve regeneration

Nerve guidance conduit (NGC) is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment using physical and/or chemical guidance cues. In this study, a neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel that could promote PC12 cell adhesion, proliferation, and neuronal differentiation in vitro was prefilled in the lumen of a hollow chitosan tube (hCST) to accelerate axonal regeneration in a rat sciatic nerve defect model. The functionalized self-assembling peptide was developed by introducing a neurotrophic peptide (RGI, RGIDKRHWNSQ) derived from brain-derived neurotrophic factor (BDNF) to the C-terminus of the self-assembling peptide RADA16-I (Ac-(RADA)₄-CONH₂). Morphological, histological, electrophysiological, and functional analyses demonstrated that the RGI-functionalized, self-assembling, peptide nanofiber hydrogel RAD/RGI could produce a neurotrophic microenvironment that markedly improved axonal regeneration with enhanced re-myelination and motor functional recovery.