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Shuai C, et al.

           limbs. The results showed that the average trabecular   bone-related diseases such as fracture, osteoporosis,
           thickness, bone mineral content and bone volume     bone delayed union or nonunion, etc., owing to their
           fraction increased 12%, 14% and 15%, respectively.   non-invasive, no infection, no side effects and ease of
           Lambers et al. [134]  studied the effects of cyclically load   use [120,126,138] . In vivo studies, many researchers implanted
           of 8 N on the bone formation and resorption of mouse   magnet rods, magnetic plates and magnetic washers
           tail vertebrae. The results showed that the 8 N group   into bone defect sites to construct static magnetic
           significantly increased trabecular bone volume fraction   field [118,121-124,139,140] . Some researchers constructed static
           and cortical area fraction. Moreover, the bone strength   magnetic field stimulation equipment composed of
           increased due to the increasing of bone formation area   magnetic plates which fixed on outside of cage (Figure
           and the decreasing of bone resorption area (Figure 7).   8A) [120]  or utilized signal generator to produce direct
           Peptan et al. [135]  investigated the effects of cyclic tensile   current which transferred to a pair of Helmholtz coils to
           or compressive forces (1 N, 8 Hz) on remodeling and   expose animals [141] . In vitro studies, the static magnetic
           growth of intramembranous bone and cranial sutures   field exposure systems which used to expose bone cells
           of rabbit models. The results showed that the high-  had various modes, such as magnets, a magnetic shield
           frequency cyclic tensile and compressive forces both   box, parallel arranged magnetic plates, etc. [36,142–146] .
           induced the modeling and growth of cranial sutures.  The construction of pulse electromagnetic field usually
                                                               adopted the tunable pulse generator to produce pulse
           5. The Equipments of Physical Stimulation           current with specific frequency, waveform and peak [147] .
           Systems                                             Jing et al. [136]  designed a pulse electromagnetic field

           In vitro and in vivo studies had shown that different   generator consists of three identical Helmholtz coils
           physical stimulations had different effects on bone   (Figure 8B), it could output different waveforms and
           cells. As the source of physical stimulations, the   parameters.
           physical stimulation systems play an important role in   5.2  The Electric Stimulation Systems
           bone repair. To date, there are no unified stimulation
           systems for each kind of physical stimulation, and the   In vivo studies, the modes of electrical stimulations
           representative physical stimulation systems are shown in   were mainly including invasive, semi-invasive and non-
           Figure 8.                                           invasive way in bone repair. The invasive way meant of
                                                               embedding cathode and anode in the injury sites [148,149] ,
           5.1  The Magnetic Stimulation Systems               and the semi-invasive way meant of embedding the

           The static magnetic field and pulse electromagnetic   cathode into the injury sites and placing the anode in
                                                                                         [150,151]
           field were widely used in the treatment of various   a cephalad paraspinous locus  . The non-invasive



                       A                                                      B










                                                                              C












           Figure 7.  Bone microstructure of mice in the 8 N and 0 N group in vivo micro-CT scans (A). The trabecular structure of the 8 N group
           was thickening with increasing stimulation time and had little changes in 0 N group. Curves of dynamic bone formation rate (B) and bone
           resorption rate (C) over time. The bone formation rate of 8 N group was obviously higher than 0 N group and the bone resorption rate
           showed the opposite result. [134]

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