  Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) are considered a
great promise in the repair and regeneration of bone. Considerable efforts have
been oriented towards uncovering the best strategy to promote stem cells
osteogenic differentiation. In previous studies, hBM-MSCs exposed to physical
stimuli such as pulsed electromagnetic fields (PEMFs) or directly seeded on
nanostructured titanium surfaces ($TiO_{2}$) were shown to improve their
differentiation to osteoblasts in osteogenic condition. In the present study,
the effect of a daily PEMF-exposure on osteogenic differentiation of hBM-MSCs
seeded onto nanostructured $TiO_{2}$ (with clusters under 100 nm of dimension)
was investigated. $TiO_{2}$-seeded cells were exposed to PEMF (magnetic field
intensity: 2 mT; intensity of induced electric field: 5 mV; frequency: 75 Hz)
and examined in terms of cell physiology modifications and osteogenic
differentiation. Results showed that PEMF exposure affected $TiO_{2}$-seeded
cells osteogenesis by interfering with selective calcium-related osteogenic
pathways, and greatly enhanced hBM-MSCs osteogenic features such as the
expression of early/late osteogenic genes and protein production (e.g., ALP,
COL-I, osteocalcin and osteopontin) and ALP activity. Finally, PEMF-treated
cells resulted to secrete into conditioned media higher amounts of BMP-2, DCN
and COL-I than untreated cell cultures. These findings confirm once more the
osteoinductive potential of PEMF, suggesting that its combination with
$TiO_{2}$ nanostructured surface might be a great option in bone tissue
engineering applications.
