A novel role in skeletal segment regeneration of extracellular vesicles released from periodontal-ligament stem cells

Francesca Diomede, Marco D'Aurora, Agnese Gugliandolo, Ilaria Merciaro, Valeria Ettorre, Alessia Bramanti, Adriano Piattelli, Valentina Gatta, Emanuela Mazzon, Antonella Fontana, Oriana Trubiani

Research output: Contribution to journalArticlepeer-review


Purpose: The combination of oral derived stem cells and 3-D scaffolds is considered advantageous in bone repair. In particular, collagen membranes possess ideal biological properties and can support infiltration and proliferation of osteoblasts, promoting bone regeneration. Our study aimed to develop a new biocompatible osteogenic construct composed of a commercially available collagen membrane (Evolution [Evo]), human periodontal-ligament stem cells (hPDLSCs) enriched with extracellular vesicles (EVs), or polyethylenimine (PEI)-engineered EVs (PEI-EVs).

Methods: Osteogenic ability and expression of osteogenic genes were evaluated in vitro in hPDLSCs cultured with or without Evo, with Evo and EVs, or PEI-EVs. In addition, the bone-regeneration capacity of Evo, Evo enriched with hPDLSCs, Evo enriched with hPDLSCs and EVs/PEI-EVs was investigated in rats subjected to calvarial defects.

Results: Our results showed that Evo enriched with EVs and PEI-EVs showed high biocompatibility and osteogenic properties in vitro and in vivo. In addition, quantitative reverse-transcription polymerase chain reaction demonstrated the upregulation of osteogenic genes, such as TGFB1, MMP8, TUFT1, TFIP11, BMP2, and BMP4, in the presence of PEI-EVs. Upregulation of BMP2/4 was confirmed for Evo enriched with PEI-EVs and hPDLSCs both in vitro by Western blot and in vivo by immunofluorescence.

Conclusion: Our results indicated that Evo enriched with hPDLSCs and PEI-EVs is able to promote a bone-regeneration process for the treatment of calvarium and ossification defects caused by accidental or surgery trauma. In particular, PEI-EVs had a significant role in activation of the osteogenic process.

Original languageEnglish
Pages (from-to)3805-3825
Number of pages21
JournalInternational Journal of Nanomedicine
Publication statusPublished - Jun 29 2018


  • Animals
  • Bone Morphogenetic Protein 2/metabolism
  • Bone Morphogenetic Protein 4/metabolism
  • Bone Regeneration/drug effects
  • Cell Differentiation/drug effects
  • Cells, Cultured
  • Collagen/pharmacology
  • Extracellular Vesicles/metabolism
  • Gene Expression Regulation/drug effects
  • Gene Regulatory Networks
  • Humans
  • Male
  • Osteogenesis/drug effects
  • Periodontal Ligament/cytology
  • Polyethyleneimine/chemistry
  • Rats, Wistar
  • Skull/pathology
  • Stem Cells/cytology


Dive into the research topics of 'A novel role in skeletal segment regeneration of extracellular vesicles released from periodontal-ligament stem cells'. Together they form a unique fingerprint.

Cite this