Biomedical Engineering Reference
In-Depth Information
Similarly, micro-/nanotopography supplies local and stable cue (Kim et al.
2012
).
In
vivo
effectiveness of micro-/nanotopography has been shown, for instance, in regu-
lation of phenotypic behavior of endothelial cells by means of topographical repli-
cas of the basement membrane (Goodman et al.
1996
) and in cancer cell invasion,
metastasis, and progression by means of 3D connective-tissue models (Lu et al.
2012
; Wolf et al.
2009
; Tozluoglu et al.
2013
).
As expected, implantable biomaterials with well-defi ned micro-/nanotopogra-
phy can provide local cues effectively. The effectiveness has been shown in a study
demonstrating that micro-/nanotopography of osteoconductivity of a porous tita-
nium implant affects effi ciency of bone formation
in vivo
(de Wild et al.
2013
). In
addition, another study show that aligned electrospun nanofi bers guide tendon stem/
progenitor cells
in vivo
to tendon differentiation (Yin et al.
2010
).
Based on these
in vivo
basic biological and applied studies, meaning of topo-
graphical and mechanical cues provided by a synthetic ECM is that it can serve as
stable and local cues in synergy with diffusive soluble factors.
11.5
Conclusion
Based on the insights shown in Sect.
11.3
, designing topography with well-defi ned
elastic modulus can implement modulation of the actin cytoskeleton in synthetic
ECM. As described in Sect.
11.2
, the physiological role of actin cytoskeleton is not
only mechanical support and force generation, but regulation of cell fate. Thus,
modulation of the actin cytoskeleton achieves combinatorial control of cell migra-
tion, cell proliferation, and stem cell differentiation. One design strategy for modu-
lation of the actin cytoskeleton is to reproduce the actin cytoskeletal behaviors that
occur in the course of a desired cell function and fate based on the analysis of how
the actin cytoskeletal system defi nes the desired cell function and fate.
A standard rule to defi ne topography for modulation of actin cytoskeletal system
is that topographical features are utilized as structural constraints at multiple levels,
as explained in Sect.
11.3.1
. In addition, as suggested in Sect.
11.3.2
, effectiveness
of a structural constraint can be tuned by its elastic modulus. In general, a greater
effect of the structural constraint could be acquired by increasing the elastic modu-
lus within the range of soft tissues: between 0.01 kPa and 100 kPa (Discher et al.
2009
; Collier et al.
2010
).
Micro-/nano-topography is a cue with a solid state, thus, the designed micro-/
nano-topography has an advantage as a cue to provide inputs at high spatial resolu-
tion (Kim et al.
2012
). It is necessary for cell and tissue culture in cell-based thera-
pies to control cell migration, the balance between proliferation and apoptosis, and
stem cell differentiation. These cell behaviors are controlled not only by the pres-
ence or absence of guiding cues but also by their absolute and relative amounts and
by spatial arrangement at the subcellular resolution. Different types of micro-/nano-
topographical and mechanical cues will fulfi ll these requirements. To fully elicit the
potential of the designed micro-/nanotopography of synthetic ECM in functional
