Regeneration of Rat Sciatic Nerve Using PLGA Conduit Containing Rat ADSCs with Controlled Release of BDNF and Gold Nanoparticles

J Mol Neurosci. 2021 Apr;71(4):746-760. doi: 10.1007/s12031-020-01694-6. Epub 2020 Oct 7.

Abstract

Implantation of a nerve guidance conduit (NGC) carrying neuroprotective factors is promising for repairing peripheral nerve injury. Here, we developed a novel strategy for repairing peripheral nerve injury by gold nanoparticles (AuNPs) and brain-derived neurotrophic factor (BDNF)-encapsulated chitosan in laminin-coated nanofiber of Poly(l-lactide-co-glycolide) (PLGA) conduit and transplantation of rat adipose-derived stem cells (r-ADSCs) suspended in alginate. Then, the beneficial effect of AuNPs, BDNF, and r-ADSCs on nerve regeneration was evaluated in rat sciatic nerve transection model. In vivo experiments showed that the combination of AuNPs- and BDNF-encapsulated chitosan nanoparticles in laminin-coated nanofiber of PLGA conduit with r-ADSCs could synergistically facilitate nerve regeneration. Furthermore, the in vivo histology, immunohistochemistry, and behavioral results demonstrated that the AuNPs- and BDNF-encapsulated chitosan nanoparticles in NGC could significantly reinforce the repair performance of r-ADSCs, which may also contribute to the therapeutic outcome of the AuNPs, BDNF, and r-ADSCs strategies. In this study, we found that the combination of AuNPs and BDNF releases in NGC with r-ADSCs may represent a new potential strategy for peripheral nerve regeneration.

Keywords: Adipose-derived stem cells; Brain-derived neurotrophic factor; Controlled release; Gold nanoparticle; Nerve conduit; Poly(L-lactide-co-glycolide).

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Brain-Derived Neurotrophic Factor / administration & dosage
  • Brain-Derived Neurotrophic Factor / therapeutic use
  • Cells, Cultured
  • Chitosan / chemistry
  • Drug Liberation
  • Gold / chemistry
  • Guided Tissue Regeneration / methods*
  • Laminin / chemistry
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Metal Nanoparticles / chemistry
  • Nerve Regeneration*
  • Peripheral Nerve Injuries / therapy*
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Rats
  • Rats, Wistar
  • Sciatic Nerve / injuries*
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / physiology
  • Tissue Scaffolds / chemistry*

Substances

  • Brain-Derived Neurotrophic Factor
  • Laminin
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Gold
  • Chitosan