title: Barium titanate nanoparticles and hypergravity stimulation improve differentiation of mesenchymal stem cells into osteoblasts.
abstract: BACKGROUND
  Enhancement of the osteogenic potential of mesenchymal stem cells (MSCs) is highly desirable in the field of bone regeneration. This paper proposes a new approach for the improvement of osteogenesis combining hypergravity with osteoinductive nanoparticles (NPs).
  
  
  METHODS
  In this study, we aimed to investigate the combined effects of hypergravity and barium titanate NPs (BTNPs) on the osteogenic differentiation of rat MSCs, and the hypergravity effects on NP internalization. To obtain the hypergravity condition, we used a large-diameter centrifuge in the presence of a BTNP-doped culture medium. We analyzed cell morphology and NP internalization with immunofluorescent staining and coherent anti-Stokes Raman scattering, respectively. Moreover, cell differentiation was evaluated both at the gene level with quantitative real-time reverse-transcription polymerase chain reaction and at the protein level with Western blotting.
  
  
  RESULTS
  Following a 20 g treatment, we found alterations in cytoskeleton conformation, cellular shape and morphology, as well as a significant increment of expression of osteoblastic markers both at the gene and protein levels, jointly pointing to a substantial increment of NP uptake. Taken together, our findings suggest a synergistic effect of hypergravity and BTNPs in the enhancement of the osteogenic differentiation of MSCs.
  
  
  CONCLUSIONS
  The obtained results could become useful in the design of new approaches in bone-tissue engineering, as well as for in vitro drug-delivery strategies where an increment of nanocarrier internalization could result in a higher drug uptake by cell and/or tissue constructs.
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @ SSSA, Pontedera, Italy ; Scuola Superiore Sant'Anna, The BioRobotics Institute, Pontedera, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Rocca
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @ SSSA, Pontedera, Italy ; Scuola Superiore Sant'Anna, The BioRobotics Institute, Pontedera, Italy.
authors.forename: Attilio
authors.initials: A
authors.lastname: Marino
authors.affiliation: Università di Pisa, Dipartimento di Ingegneria dell'Informazione, Pisa, Italy, Noordwijk, the Netherlands.
authors.forename: Veronica
authors.initials: V
authors.lastname: Rocca
authors.affiliation: Università di Pisa, Dipartimento di Medicina Clinica e Sperimentale, Pisa, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Moscato
authors.affiliation: Istituto Italiano di Tecnologia, Center for Nanotechnology Innovation @NEST, Pisa, Italy ; Scuola Normale Superiore, NEST, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: de Vito
authors.affiliation: Istituto Italiano di Tecnologia, Center for Nanotechnology Innovation @NEST, Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Piazza
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @ SSSA, Pontedera, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mazzolai
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @ SSSA, Pontedera, Italy.
authors.forename: Virgilio
authors.initials: V
authors.lastname: Mattoli
authors.affiliation: Directorate of Human Spaceflight and Operations, European Space Agency, Noordwijk, the Netherlands.
authors.forename: Thu Jennifer
authors.initials: TJ
authors.lastname: Ngo-Anh
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @ SSSA, Pontedera, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Ciofani
mesh_terms: D000818:Animals; D017609:Barium Compounds / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D018471:Hypergravity; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology
chemical_list: D017609:Barium Compounds; C024547:barium titanate(IV); D014025:Titanium
keywords: barium titanate nanoparticles; hypergravity; mesenchymal stem cells; osteogenesis