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Peer-reviewedCC BYScientific Reports

Sustained simvastatin delivery via poly(lactide) nanoparticles enhances early osteogenic-associated responses in human periodontal ligament stem cells

  • Tomaz Alves1
  • Priscila Lucena Mendes2
  • Marlus da Silva Pedrosa3
  • Danilo Balzarini2
  • Letícia Miquelitto Gasparoni4
  • Aldrin Huamán-Mendoza2
  • Bruno Nunes de França5
  • Danillo Fabrini Maciel Costa Veloso6
  • Eliana Martins Lima6
  • Carla Renata Sipert7
  • Carlos Adde2
  • Marinella Holzhausen2
7 affiliations
  1. 1Department of Developmental and Surgical Sciences, Division of Periodontology, School of Dentistry, University of Minnesota
  2. 2Department of Stomatology, Division of Periodontics, School of Dentistry, University of São Paulo
  3. 3Department of Orofacial Sciences, School of Dentistry, University of California
  4. 4Department of Dental Clinics, Division of Periodontics, School of Dentistry, University of Juiz de Fora
  5. 5School of Dentistry, Universidade São Francisco - USF
  6. 6School of Pharmacy, Federal University of Goiás
  7. 7Department of Restorative Dentistry, School of Dentistry, University of Sao Paulo
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Abstract

Simvastatin has recognized osteoinductive properties, but its application in regenerative strategies is limited by poor aqueous behavior and a narrow cytocompatible dosing window. Here, we developed simvastatin-loaded poly(lactide) nanoparticles and evaluated whether nanoparticle-mediated delivery improves cytocompatibility and early osteogenic-associated responses of human periodontal ligament stem cells (hPDLSCs) compared with free simvastatin. Nanoparticles were prepared by nanoprecipitation and characterized by dynamic light scattering, transmission electron microscopy, and nanoparticle tracking analysis, showing spherical morphology and a mean diameter of approximately 150 nm. Cellular internalization was confirmed using rhodamine-labeled nanoparticles and confocal microscopy, demonstrating efficient uptake with predominantly cytoplasmic localization. In hPDLSCs, nanoparticle-delivered simvastatin improved short-term cytocompatibility and enhanced mineralization together with increased periostin and osteocalcin secretion, with the most pronounced differences observed at day 14, whereas mineralization outcomes converged between delivery formats by day 21. Complementary clonogenic assays in osteoblasts demonstrated that nanoparticle-mediated delivery attenuated simvastatin-associated loss of long-term proliferative capacity relative to free simvastatin under the tested conditions. These findings indicate that poly(lactide) nanoparticles may improve the cytocompatible delivery profile of simvastatin and preferentially enhance early osteogenic-associated responses in vitro in hPDLSCs, supporting further investigation of controlled simvastatin delivery strategies for periodontal regenerative applications.

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Cite

BibTeXRIS
BibTeX
@article{alves2026sustained,
  title = {{Sustained simvastatin delivery via poly(lactide) nanoparticles enhances early osteogenic-associated responses in human periodontal ligament stem cells}},
  author = {Tomaz Alves and Priscila Lucena Mendes and Marlus da Silva Pedrosa and Danilo Balzarini and Letícia Miquelitto Gasparoni and Aldrin Huamán-Mendoza and Bruno Nunes de França and Danillo Fabrini Maciel Costa Veloso and Eliana Martins Lima and Carla Renata Sipert and Carlos Adde and Marinella Holzhausen},
  journal = {Scientific Reports},
  year = {2026},
  month = jul,
  doi = {10.1038/s41598-026-63776-6},
  url = {https://doi.org/10.1038/s41598-026-63776-6},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Sustained simvastatin delivery via poly(lactide) nanoparticles enhances early osteogenic-associated responses in human periodontal ligament stem cells
AU  - Tomaz Alves
AU  - Priscila Lucena Mendes
AU  - Marlus da Silva Pedrosa
AU  - Danilo Balzarini
AU  - Letícia Miquelitto Gasparoni
AU  - Aldrin Huamán-Mendoza
AU  - Bruno Nunes de França
AU  - Danillo Fabrini Maciel Costa Veloso
AU  - Eliana Martins Lima
AU  - Carla Renata Sipert
AU  - Carlos Adde
AU  - Marinella Holzhausen
PY  - 2026
DA  - 2026/07/01
JO  - Scientific Reports
DO  - 10.1038/s41598-026-63776-6
UR  - https://doi.org/10.1038/s41598-026-63776-6
AB  - Simvastatin has recognized osteoinductive properties, but its application in regenerative strategies is limited by poor aqueous behavior and a narrow cytocompatible dosing window. Here, we developed simvastatin-loaded poly(lactide) nanoparticles and evaluated whether nanoparticle-mediated delivery improves cytocompatibility and early osteogenic-associated responses of human periodontal ligament stem cells (hPDLSCs) compared with free simvastatin. Nanoparticles were prepared by nanoprecipitation and characterized by dynamic light scattering, transmission electron microscopy, and nanoparticle tracking analysis, showing spherical morphology and a mean diameter of approximately 150 nm. Cellular internalization was confirmed using rhodamine-labeled nanoparticles and confocal microscopy, demonstrating efficient uptake with predominantly cytoplasmic localization. In hPDLSCs, nanoparticle-delivered simvastatin improved short-term cytocompatibility and enhanced mineralization together with increased periostin and osteocalcin secretion, with the most pronounced differences observed at day 14, whereas mineralization outcomes converged between delivery formats by day 21. Complementary clonogenic assays in osteoblasts demonstrated that nanoparticle-mediated delivery attenuated simvastatin-associated loss of long-term proliferative capacity relative to free simvastatin under the tested conditions. These findings indicate that poly(lactide) nanoparticles may improve the cytocompatible delivery profile of simvastatin and preferentially enhance early osteogenic-associated responses in vitro in hPDLSCs, supporting further investigation of controlled simvastatin delivery strategies for periodontal regenerative applications.
SN  - 2045-2322
ER  -