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Physical stimulations and their osteogenesis-inducing mechanisms

physical stimulations (such as magnetic or conductive osteoblasts in all scaffolds, and the enhancement of
materials) is a promising and efficient candidate for bone bone mineralization in PCL/-TCP scaffold was the
formation and healing. highest (Figure 4A). The results indicated that the
The physical stimulations combined with bone electric stimulation and scaffold materials both played
scaffolds has great potential in bone repair because a significant role in bone repair. Sun et al. [111] reported
they can fully reflect the synergetic effects of bone that the electric stimulation induced the reorientation
scaffolds and physical fields in bone repair process. of fibroblasts in three-dimensional collagen scaffold
[66]
Yun et al. found that static magnetic field synergized and along the direction of the electric stimulation. Chen
with magnetic bone scaffolds promoted the osteoblastic et al. [96] investigated synergistic action of fluid shear
differentiation including enhanced alkaline phosphatase stress and three-dimensional porous scaffolds (collagen/
activity and up-regulated gene expressions of osterix hydroxyapatite, Col/HA) on the biological behaviors of
and runt-related transcription factor 2. Feng et al. [67] mesenchymal stem cells. The results showed that the
investigated the bioeffects of 4000 G static magnetic viability of mesenchymal stem cells in the all scaffolds
field on the osteoblasts cultured on poly-L-lactide was significantly increased under oscillatory shear stress
substrates surface and found that alkaline phosphatase cultured for 3 weeks compared with control group.
activity was significantly increased, indicating that static Moreover, the oscillatory shear stress significantly
magnetic field combined with scaffolds could promote enhanced the osteogenic differentiation of mesenchymal
cell differentiation. Arjmand et al. [108] proved that the stem cells in the scaffolds (Figure 4B).
extremely low frequency pulse electromagnetic field 4. In vivo Studies of Physical Stimulation
combined with polycaprolactone (PCL) nanofibrous
scaffold significantly enhanced the proliferation and In vivo studies mainly include animal experiments
osteogenic differentiation of mesenchymal stem cells and clinical trials. Animal experiments can provide
by analyzing alizarin red staining, alkaline phosphatase theoretical supports for clinical trials. Many animal
activity, calcium content, related genes expressions experiments and clinical trials have been carried out
such as collagen type I, runt-related gene 2, osteonectin to determine the effects of magnetic, electric and
and osteocalcin. Some studies have shown that scaffold mechanical stimulation on bone repair [112–115] .
materials have a significant impact on bone repair [109,110] .
[79]
Jin et al. investigated the effects of electric stimulation 4.1 In vivo Studies of Magnetic Stimulation
combined with three-dimensional porous scaffolds (PCL, The magnetic stimulation produced by magnetic fields
PCL/carbon nanotubes (CNT) and PCL/ -tricalcium and electromagnetic fields could conduce to accelerate
phosphate (-TCP) scaffold) on the osteoblasts. They bone repair due to that they could promote bone
found that the electric stimulation enhanced the alkaline formation and inhibit bone resorption [116–119] . Taniguchi et
phosphatase activity and calcium mineralization of

A B
A1 A2 B1 B4 B7 B10

A3 A4 B2 B5 B8 B11

A5 A6 B3 B6 B9 B12

Figure 4. (A) Live/dead assay of MG63 cells seeded on PCL (A1, A2), PCL/CNT (A3, A4), and PCL/-TCP scaffolds (A5, A6) with and
without electric stimulation after 14 days . (B) Live/dead assay of mesenchymal stem cells seeded on the midline section of different
[79]
scaffolds for 1, 2, and 3 weeks under oscillatory perfusion. (B1-B3) Static culture mesenchymal stem cells. The scale bar indicates 50 μm.
Living cells (green) and dead cells (red) .
[96]
8 International Journal of Bioprinting (2018)–Volume 4, Issue 2