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

The effect of pulsed electromagnetic field exposure on osteoinduction of human mesenchymal stem cells cultured on nano-$TiO_{2}$ surfaces