Urethroplasty with a bilayered poly-D,L-lactide-co-ε-caprolactone scaffold seeded with allogenic mesenchymal stem cells

J Biomed Mater Res B Appl Biomater. 2020 Apr;108(3):1010-1021. doi: 10.1002/jbm.b.34453. Epub 2019 Aug 1.

Abstract

Reconstructive surgery for urethral defects employing tissue-engineered scaffolds represents an alternative treatment for urethroplasty. The aim of this study was to compare the therapeutic efficacy of the bilayer poly-D,L-lactide/poly-ε-caprolactone (PL-PC) scaffold seeded with allogenic mesenchymal stem cells (MSCs) for urethra reconstruction in a rabbit model with conventional urethroplasty employing an autologous buccal mucosa graft (BG). The inner layer of the scaffold based on poly-D,L-lactic acid (PL) was seeded with MSCs, while the outer layer, prepared from poly-ε-caprolactone, protected the surrounding tissues from urine. To track the MSCs in vivo, the latter were labeled with superparamagnetic iron oxide nanoparticles. In rabbits, a dorsal penile defect was reconstructed employing a BG or a PL-PC graft seeded with nanoparticle-labeled MSCs. In the 12-week follow-up period, no complications were detected. Subsequent histological analysis demonstrated biointegration of the PL-PC graft with surrounding urethral tissues. Less fibrosis and inflammatory cell infiltration were observed in the experimental group as compared with the BG group. Nanoparticle-labeled MSCs were detected in the urothelium and muscular layer, co-localizing with the urothelium cytokeratin marker AE1/AE3, indicating the possibility of MSC differentiation into neo-urothelium. Our results suggest that a bilayer MSCs-seeded scaffold could be efficiently employed for urethroplasty.

Keywords: bilayer scaffold; buccal graft; mesenchymal stem cells; superparamagnetic iron oxide nanoparticles; urethral substitution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Chinchilla
  • Chondrocytes / cytology
  • Ferric Compounds / chemistry
  • Inflammation
  • Lipid Bilayers
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Metal Nanoparticles / chemistry
  • Mouth Mucosa / pathology
  • Nanoparticles / chemistry
  • Polyesters / chemistry*
  • Rabbits
  • Tissue Engineering / instrumentation*
  • Tissue Scaffolds / chemistry
  • Transplantation, Homologous
  • Urethra / surgery*
  • Urothelium / metabolism

Substances

  • Ferric Compounds
  • Lipid Bilayers
  • Polyesters
  • ferric oxide
  • lactide-caprolactone copolymer