Neuregulin-1 released by biodegradable gelatin hydrogels can accelerate facial nerve regeneration and functional recovery of traumatic facial nerve palsy

Abstract

Neuregulin-1 is an essential axoglial signal required for peripheral nerve development, and evidence that neuregulin-1 is also required for effective nerve repair is growing. In this study, the effects of neuregulin-1-impregnated gelatin hydrogels on nerve regeneration and functional recovery after anastomosis of the facial nerve were investigated in a rat model of traumatic facial nerve paralysis. Twenty-four adult male rats underwent complete resection of thefacial nerve trunk, followed by end-to-end anastomosis with epineural sutures. The animals were then randomly allocated to one of three treatment groups (eight rats/group): no additional intervention (Group I), single-shot injection of neuregulin-1 into the epineurium of the facial nerve at the suture sites (Group II), or implantation of a hydrogel impregnated with neuregulin-1 at the injury site (Group III). After surgery, mimetic muscle movements were evaluated weekly. Eight weeks after surgery, the mimetic muscles were injected witha neural tracer (1,10-dioctadecyl-3,3,30,30-tetramethylindocarbocyanin perchlorate, DiI). Retrograde-labeled neurons were counted in the facial nuclei, and facial nerve specimens were stained with toluidine blue for histological examination of axon density. Group III exhibited significantly faster recovery of mimetic muscle function, a higher density of large-diameter axons (>5μm) in the facial nerve, and greater numbers of retrogradely labeled neurons in the ipsilateral facial nucleus compared with Groups I and II. Continuous release of neuregulin-1 from impregnated gelatin hydrogels can accelerate facial nerve regeneration.