title: Boron nitride nanotubes and primary human osteoblasts: in vitro compatibility and biological interactions under low frequency ultrasound stimulation.
abstract: In this paper we investigated a novel and non-invasive approach for an endogenous osteoblast stimulation mediated by boron nitride nanotubes (BNNTs). Specifically, following the cellular uptake of the piezoelectric nanotubes, cultures of primary human osteoblasts (hOBs) were irradiated with low frequency ultrasound (US), as a simple method to apply a mechanical input to the cells loaded with BNNTs. This in vitro study was aimed at investigating the main interactions between hOBs and BNNTs and to study the effects of the 'BNNTs + US' stimulatory method on the osteoblastic function and maturation.A non-cytotoxic BNNT concentration to be used in vitro with hOB cultures was established. Moreover, investigation with transmission electron microscopy/electron energy loss spectroscopy (TEM/EELS) confirmed that BNNTs were internalized in membranal vesicles. The panel of investigated osteoblastic markers disclosed that BNNTs were capable of fostering the expression of late-stage bone proteins in vitro, without using any mineralizing culture supplements. In our samples, the maximal osteopontin expression, with the highest osteocalcin and Ca(2+) production, in the presence of mineral matrix with nodular morphology, was observed in the samples treated with BNNTs + US. In this group was also shown a significantly enhanced synthesis of TGF-β1, a molecule sensitive to electric stimulation in bone. Finally, gene deregulations of the analyzed osteoblastic genes leading to depletive cellular effects were not detected. Due to their piezoelectricity, BNNT-based therapies might disclose advancements in the treatment of bone diseases.
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Emergency Medicine, University of Pisa, via Paradisa 2, I-56124 Pisa, Italy. Center for the Clinical Use of Stem Cells-Regional Network of Regenerative Medicine 'CUCCS-RRMR', University of Pisa, via Roma 55, I-56126 Pisa, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Danti
authors.forename: Gianni
authors.initials: G
authors.lastname: Ciofani
authors.forename: Stefania
authors.initials: S
authors.lastname: Moscato
authors.forename: Delfo
authors.initials: D
authors.lastname: D'Alessandro
authors.forename: Elena
authors.initials: E
authors.lastname: Ciabatti
authors.forename: Claudia
authors.initials: C
authors.lastname: Nesti
authors.forename: Rosaria
authors.initials: R
authors.lastname: Brescia
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bertoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Pietrabissa
authors.forename: Michele
authors.initials: M
authors.lastname: Lisanti
authors.forename: Mario
authors.initials: M
authors.lastname: Petrini
authors.forename: Virgilio
authors.initials: V
authors.lastname: Mattoli
authors.forename: Stefano
authors.initials: S
authors.lastname: Berrettini
mesh_terms: D001896:Boron Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D008422:Materials Testing; D043942:Nanotubes / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D011107:Polylysine; D013016:Sound
chemical_list: D001896:Boron Compounds; D011107:Polylysine; C017282:boron nitride