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Physical stimulations and their osteogenesis-inducing mechanisms

           way referred to place the injury sites in an electric   5.3  The Mechanical Stimulation Systems
           field or place the electrodes on the surface of the
           treatment sites [152,153] . It had been widely accepted by   Low intensity pulsed ultrasound treatment had received
           patients owing to the small trauma. In vitro studies,   widespread attention in treatment bone fracture due to
           some researchers placed electrodes on top and bottom   the advantages of safety, non-invasive, no infection and
                                                                              [155]
           surfaces of each well and then connected the electric   less complication  . The ultrasonic stimulation used
           field device to stimulate cells [154] . Many researchers used   by most researchers was usually generated by the Sonic
           sinusoidal alternating electric field which consisted of   Accelerated Fracture Healing System, which could
                                                                                                       [81,156,157]
           function generator and parallel electrodes to expose   pro duce different frequencies and intensities  .
                                 [14]
           bone cells [49,79] . Kim et al.  designed a biphasic electric   Different devices were used to carry out different
           current system to stimulate osteoblasts which consisted   mechanical stimulations for bone cells and tissues. The
           of Teflon® culture dish, two evaporated Au plates,   BiopressTM system was used by many researchers to
           media and biphasic current stimulator. The anodes   apply compressive loads. It could control load magnitude
           and cathodes of each well were connected to form an   to compress osteoblasts membrane to investigate the
                                                                                                         [137,158]
           electrical shunt configuration and all electrodes were   effects of compression stress on osteoblasts   .
                                                                         [159]
           connected to the biphasic electric current stimulator chip   Zhong et al.   designed a cellular cyclic tension and
                                 [75]
           (Figure 8D). Banks et al.  customized an ibidi device   compression apparatus to investigate the biological
           to create an electric field stimulation system which   response of osteoblasts under stretching or compressing.
           allowed to simultaneously stimulate six cell migration   The apparatus could control the carrier rod to precisely
           chambers, and 6 pairs of agar bridges in physiologic   shift up and down. Many researchers used a parallel-
           buffered saline connected cell migration channels to   plate flow chamber to induce fluid flow over the cells
                                                                                        [93,94,160,161]
                                                                                                         [162–164]
           reservoirs of physiologic buffered saline, in which Ag-  to construct fluid shear stress  . You et al.
           AgCl electrodes were immersed (Figure 8E).          established a flow system which was driven by an
                                                               electromagnetic actuator.

                              A                   B                    C










                             D                    E                    F









                              G                                       H











           Figure 8. The schematic of the physical stimulation systems. (A) static magnetic field exposure system [120] . (B) pulse electromagnetic field
           exposure system [136] . (C) Magnetic stimulation on artificial bone . (D) Biphasic electric current stimulation system . (E) Direct current
                                                                                               [14]
                                                         [66]
           electric stimulation system . (F) Electric stimulation consisted of a parallel electrode used to stimulate cells seeded on scaffold . (G)
                              [75]
                                                                                                         [79]
           Flexercell compression plus system was used to compress osteoblasts membrane [137] . (H) Mechanical stimulation bioreactor system was
                                         [22]
           used to perfuse scaffolds seeded with cells .
           12                          International Journal of Bioprinting (2018)–Volume 4, Issue 2
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