A Laminin-2-Derived Peptide Promotes Early-Stage Peripheral Nerve Regeneration in Vivo

Objectives: Peptides have been recognized as a valuable scientific tool in the field of tissue engineering. The DLTIDDSYWYRI motif (Ln2-P3) of the human laminin-2 á2 chain has been previously reported to promote PC12 cell attachment through syndecan-1 by inducing phosphorylation and membrane localization of protein kinase C; however, the in vivo effects of the Ln2-P3 have not yet been studied. The aim of this study is to evaluate the possibility that a laminin-2-derived peptide can promote peripheral nerve regeneration by acting nerve growth-promoting substance in vivo. Methods: To examine this hypothesis, we developed a dual-component artificial nerve graft with an outer microporous conduit using poly(lactic-co-glycolic acid) (PLGA) and an inner microporous conduit using poly(p-dioxanone) (PPD). The novel graft coated with vehicle or Ln2-P3 was used for bridging sciatic nerve across a 10-mm defect in rats. Results: Dual-component PPD/PLGA artificial nerve grafts provided a similar mechanical stability compared with real rat nerve stump. Compared with vehicle-treated and peptide-treated rat sciatic nerve repair, the application significantly promoted early-stage peripheral nerve regeneration by enhancing nerve regeneration rate, significantly increased myelinated fiber density, and notably reduced foreign body giant cell infiltration. Conclusion: These findings support our hypothesis that the DLTIDDSYWYRI motif acts as a very effective accelerator for peripheral nerve regeneration by enhancing nerve regeneration rate and increasing myelinated fiber density. This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A090648).