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Physical stimulations and their osteogenesis-inducing mechanisms
[11]
lost rapidly . Physical stimulations such as magnetic, by enhancing cell activity and promoting bone re-
electric and mechanical stimulation can constantly act on generation [33–35] . These mechanisms are responsible for
bone defect sites to enhance and maintain cell activity accelerating bone formation and bone repair.
via activating signal pathways, modulating ion channels, In this paper, the different osteogenesis-inducing
regulating bone-related gene expressions, etc. [12] More mechanisms of physical stimulations in bone repair
importantly, physical stimulations have been proved process were systematically combed. The bioeffects
to be safe and can control the bone growth direction of physical stimulations on cell behavior and bone
depending on the direction of stimulations, thereby formation which were investigated by numerous
accelerating bone formation and regeneration [13–15] . of studies in vitro and in vivo were summarized.
Magnetic stimulation is a safe and non-invasive Meanwhile, the synergetic effects of physical sti-
method to treat bone defect, which is produced by mulations and bone scaffolds especially the 3D printed
magnetic fields and electromagnetic fields, mainly bone scaffolds on cells were presented. Besides,
including static magnetic field and pulse electromagnetic the equipment of physical stimulation systems were
field stimulation [16–18] . Electric stimulation is a widely discussed, and the application prospects of these
recognized approach for stimulating bone growth, stimulations in bone repair were also analyzed.
which is produced by various currents, mainly including 2. The Osteogenesis-inducing Mechanisms of
direct current, biphasic electric current and alternating Physical Stimulations
electric current stimulation [19,20]. Mechanical stimulation
is conducive to bone regeneration and healing, which is Bone is a constantly updated tissue composed of
produced by ultrasound and other mechanical methods, metabolically active cells. Cell behaviors such as
mainly including ultrasonic, compressive stress, tensile migration, proliferation, differentiation and apoptosis
stress and fluid shear stress stimulation [21,22] . Some play a significant role in bone repair process. Physical
summaries about the physical stimulations toward bone stimulations can accelerate the proliferation and
repair applications including classify and producing differentiation of osteoblasts and inhibit the formation of
methods as well as advantages and disadvantages are osteoclasts. In order to better understand the bioeffects of
presented in Table 1 [16,23–32] . These physical stimulations physical stimulations on cell activity and bone growth,
can enhance cell activity and promote bone regeneration, the osteogenesis-inducing mechanisms of them are
which have been described as functional adaptation systematically combed according to relevant researches.
primarily owing to their osteogenesis-inducing
ability. Detailedly, Hall effect produced by magnetic 2.1 Magnetic Stimulation
stimulations, inverse piezoelectric effect induced The osteogenesis-inducing mechanisms of magnetic
by electrical stimulations and mechanotransduction stimulation were explained as follows: (1) Producing
effect caused by mechanical stimulations can change Hall effect: The moving charged ions between bone
local microenvironment of bone defect sites, alter cell matrix and osteocyte membrane would encounter a
membrane functions, activate signaling pathways, Lorentz force in magnetic field, and then form Hall
re gulate bone-related gene expressions, etc., there- voltage to induce the further migration of ions and

Table 1. Physical stimulations for bone repair.

Physical stimulations Classify Producing methods Advantages Disadvantages References
Magnetic Stimulation Static magnetic field Magnets [16,23,24]
Passing direct current Safe
through coils Non-invasive Need for additional equipment
Less well defined
No infection
Pulse electromagnetic Passing pulse current through No side effects stimulation site
field
Helmholtz coils Ease of use
Electric Stimulation Biphasic current Biphasic current stimulator [25–28]
deliver biphasic stimulation
currents Ease of operation The insufficient biocompatibility
Direct current Passing direct electric current Stable strength of electrodes can cause local
through electrodes Reproducible infection
Alternating current A generator produce
alternating current
Mechanical Ultrasonic Ultrasound Safe Difficult to apply on freely [29–32]
Stimulation Compressive stress Compressive apparatus Non-invasive moving animals
Tensile stress Tension apparatus No infection Difficult to precisely measure
Fluid shear stress Flow chamber Less complication stimulus intensity

2 International Journal of Bioprinting (2018)–Volume 4, Issue 2