Effects of hyaluronic acid and tacrolimus on the prevention of perineural scar formation and on nerve regeneration after sciatic nerve repair in a rabbit model

Abstract

Scar formation after injured peripheral nerve repair is a significant clinical problem because it prevents nerve regeneration. The aim of this study was to investigate and compare the effects of hyaluronic acid (HA) and tacrolimus (FK506) on peripheral nerve regeneration in rabbits after the drugs were topically applied at the site of nerve repair. Thirty adult male European rabbits (Oryctolagus cuniculus), ranging in weight from 2.5 to 3kg, were randomly assigned to three groups: the HA and FK506 groups comprised the experimental groups, while the saline group served as the control. At week 12, macroscopic and microscopic evaluations were performed and analyzed. In general, the macroscopic evaluations (skin and muscle fascia closure and nerve adherence), microscopic evaluations (cellular components, scar tissue formation index, and histomorphological organization), and measurements of nerve diameter and gastrocnemius muscle wet weight demonstrated the positive effects of topical application of these pharmacological agents (HA and FK506); HA and FK506 prevented scar formation and enhanced nerve regeneration. No significant differences in the parameters described above were observed between the HA and FK506 groups (P>0.05). However, significant differences were observed between both the HA and FK506 groups and the saline group (P<0.05). Based on our findings, topical application of HA and FK506 exhibits equally positive effects, preventing perineural scar formation and enhancing nerve regeneration after peripheral nerve repair.