PRGD/PDLLA conduit potentiates rat sciatic nerve regeneration and the underlying molecular mechanism

Biomaterials. 2015 Jul:55:44-53. doi: 10.1016/j.biomaterials.2015.03.028. Epub 2015 Apr 9.

Abstract

Peripheral nerve injury requires optimal conditions in both macro-environment and micro-environment for reestablishment. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the micro-environment provided by nerve conduit remains unclear. In this study, the rat sciatic nerve of 10 mm defect was made and bridged by PRGD/PDLLA nerve conduit. We investigated the process of nerve regeneration using histological, functional and real time PCR analyses after implantation from 7 to 35 days. Our data demonstrated that the ciliary neurotrophic factor highly expressed and up-regulated the downstream signaling pathways, in the case of activated signals, the expressions of axon sprout relative proteins, such as tubulin and growth-associated protein-43, were strongly augmented. Taken together, these data suggest a possible mechanism of axon regeneration promoted by PRGD/PDLLA conduit, which created a micro-environment for enhancement of diffusion of neurotrophic factors secreted by the injured nerve stumps, and activation of molecular signal transduction involved in growth cone, to potentiate the nerve recovery.

Keywords: Micro-environment; Molecular mechanism; Nerve conduit; Nerve regeneration; Singling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / pathology
  • Biocompatible Materials / chemistry
  • Biomimetics
  • Ciliary Neurotrophic Factor / metabolism
  • Cystine / chemistry
  • GAP-43 Protein / metabolism
  • Gene Expression Regulation
  • Guided Tissue Regeneration / instrumentation*
  • Guided Tissue Regeneration / methods
  • Lactic Acid / chemistry*
  • Ligands
  • Muscle, Skeletal / innervation
  • Nerve Regeneration*
  • Oligopeptides / chemistry
  • Peripheral Nerve Injuries / therapy
  • Polyesters / chemistry
  • Polymers / chemistry*
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / pathology*
  • Signal Transduction
  • Tubulin / metabolism

Substances

  • Biocompatible Materials
  • Ciliary Neurotrophic Factor
  • GAP-43 Protein
  • Ligands
  • Oligopeptides
  • Polyesters
  • Polymers
  • Tubulin
  • Lactic Acid
  • poly(lactide)
  • Cystine
  • arginyl-glycyl-aspartic acid