Biomedical Engineering Reference
In-Depth Information
In this chapter we have focused primarily on nanopatterned surfaces for stem-cell
engineering. We have investigated the techniques that can be used for fabrication of different
nanotopographical substrates and their applications to control stem-cell proliferation and
differentiation over the past few years, which include microcontact printing, self-assembly,
metal anodization, and DPN methods in stem-cell tissue engineering.
Technology for Nanopatterned Surface of Cell Chips
Dip-Pen Nanolithography
Dip-pen nanolithography is an emerging technology that has great potential for applications in
the development of surfaces, and which can be used to investigate the biological responses from
the submicron level and upwards [21, 22]. Curran's group have reported the application of DPN
to produce nanopatterned arrays of 70-nm-sized dots separated by defined spacings of 140, 280
and 1000 nm with terminal functionalities of carboxyl (-COOH), amino (-NH
2
), methyl (-CH
3
)
and hydroxyl (-OH) groups to control initial stem-cell adhesion and differentiation. These
nanopatterned surfaces can control initial cell interactions and will change the capabilities for
stem-cell definition
in vitro
and then cell-based medical therapies [23].
The same group investigated the application of DPN to produce arrays of nanodot termi-
nals with the same functionality groups over planar gold (Au) surfaces with an optimized
fixed diameter of 70 nm separated by defined spacings ranging from 140 to 1000 nm [24].
These homogeneously nanopatterned surfaces exhibited the effect of MSC differentiation
but without the need for exogenous biological factors and heavily supplemented cell media.
Whereas, with both glass and polymer surfaces as the material substrate, -CH
3
groups have
been shown to enhance the MSC phenotype, -NH
2
groups directed stem cells to become
osteogenic, that is, bone forming, and -OH and -COOH groups directed stem cells towards
a cartilaginous tissue phenotype [25].
Nanografting
Deng and his co-workers [26] have developed a method that combines micromachining with
atomic force microscopy (AFM) based nanografting [27, 28] to produce nanostructures ter-
minated with 2,4-dinitrophenyl (DNP) functional groups as an antigen. These engineered
nanostructures with a highly controlled distribution of ligand, including the geometry and
local surface environment at the molecular level, induced cellular adherence, spreading,
membrane morphology, cytoskeleton structure, and activation. In addition, the nanogrids
of 17 nm line width, 40 nm periodicity, and DNP haptens 1.4 nm above the surroundings,
induced the highest level of spreading and activation. Thus, the combination of microma-
chining and nanolithography enables hierarchical micro- and nanostructures of designed
functionalities to be produced on surfaces for directing cellular signaling processes [26].
Polymer Phase Separation
Polymer blends or block copolymers can be used as a simple method to generate micro-
and nanotopographies with a certain degree of control [29-32]. Dalby
et al.
(2004) reported
the application of a phase-separation technique to control the surface topography, based
on a spin coating of polymer solution on a glass substrate with solvent evaporation leading
to a topographical landscape with identical height [33]. In addition, Hanarp
et al.
used
colloidal particles in an ionic solution cast on the substrate, and the deposited colloids
