PLA-based mineral-doped scaffolds seeded with human periapical cyst-derived MSCs: A promising tool for regenerative healing in dentistry

Marco Tatullo, Gianrico Spagnuolo, Bruna Codispoti, Fausto Zamparini, Anqi Zhang, Micaela Degli Esposti, Conrado Aparicio, Carlo Rengo, Manuel Nuzzolese, Lucia Manzoli, Fabio Fava, Carlo Prati, Paola Fabbri, Maria Giovanna Gandolfi

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74 Scopus citations


Human periapical cyst mesenchymal stem cells (hPCy-MSCs) are a newly discovered cell population innovatively collected from inflammatory periapical cysts. The use of this biological waste guarantees a source of stem cells without any impact on the surrounding healthy tissues, presenting a valuable potential in tissue engineering and regenerative medicine applications. In the present study, hPCy-MSCs were collected, isolated, and seeded on three experimental mineral-doped porous scaffolds produced by the thermally-induced phase-separation (TIPS) technique. Mineral-doped scaffolds, composed of polylactic acid (PLA), dicalcium phosphate dihydrate (DCPD), and/or hydraulic calcium silicate (CaSi), were produced by TIPS (PLA-10CaSi, PLA-5CaSi-5DCPD, PLA-10CaSi-10DCPD). Micro-CT analysis evaluated scaffolds micromorphology. Collected hPCy-MSCs, characterized by cytofluorimetry, were seeded on the scaffolds and tested for cell proliferation, cells viability, and gene expression for osteogenic and odontogenic differentiation (DMP-1, OSC, RUNX-2, HPRT). Micro-CT revealed an interconnected highly porous structure for all the scaffolds, similar total porosity with 99% open pores. Pore wall thickness increased with the percentage of CaSi and DCPD. Cells seeded on mineral-doped scaffolds showed a superior proliferation compared to pure PLA scaffolds (control), particularly on PLA-10CaSi-10DCPD at day 12. A higher number of non-viable (red stained) cells was observable on PLA scaffolds at days 14 and 21. DMP-1 expression increased in hPCy-MSCs cultured on all mineral-doped scaffolds, in particular on PLA-5CaSi-5DCPD and PLA-10CaSi-10DCPD. In conclusion, the innovative combination of experimental scaffolds colonized with autologous stem cells from periapical cyst represent a promising strategy for regenerative healing of periapical and alveolar bone.

Original languageEnglish (US)
Article number597
Issue number4
StatePublished - Feb 16 2019

Bibliographical note

Publisher Copyright:
© 2019 by the authors.


  • Bioactive scaffolds
  • Calcium silicate-containing scaffolds
  • Human periapical cyst mesenchymal stem cells (hPCy-MSCs)
  • Polylactic acid (PLA)-based scaffolds
  • Porous scaffolds
  • Regenerative dentistry
  • Thermally induced phase separation technique (TIPS)


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