Biomedical Engineering Reference
In-Depth Information
sandblasting and subsequent chemical etching. Subsequently, a nano-
particle gradient was prepared orthogonally by gradual immersion into a
nanoparticle solution followed by sintering to firmly attach nanoparticles.
From here, the 2D gradient was replicated using PDMS to create a negative
replica, followed by a positive replica fabrication using an epoxy resin. The
final step was to sputter coat the epoxy replica with titanium. In general, an
increase in micro-roughness led to an increase in osteopontin expression (an
osteogenesis marker). This investigation of the combined effects of micro-
and nano-roughness in a single experiment revealed that whilst there was a
relatively linear response of osteopontin expression with increasing rough-
ness, there was an optimum where high micro surface roughness coupled
with moderate nano-roughness gave highest osteopontin expression. Had
these topographies been investigated separate from one another, this opti-
mal may not have been discovered.
A 2D gradient with variations in both groove pitch and depth was de-
veloped by Reynolds et al.
239
(Figure 10.21B). Dual layer etching masks were
created using a combination of micropatterning and plasma polymer de-
position. A gradient pitch was generated through the use of a gradient
photomask and photolithography. The depth axis was generated using the
same technique as described in Section 1.4.1.3. Briefly, a gradient hexane
plasma polymer was deposited orthogonally to the groove pitch gradient as a
sacrificial layer, followed by etching of the surface.
153
The attachment of
fibroblast, endothelial and epithelial cells was investigated on these 2D
gradients whereby an optimum was found for both epithelial and endo-
thelial cells as shown in Figure 10.21B(ii). No such increased cell response
region was found for fibroblast cells, however the orientation of fibroblast
cells was found to respond to the grooved/pitch 2D gradient.
d
n
3
r
4
n
g
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7
.
10.3 Conclusions
The work described in this chapter is expected to facilitate the development
of advanced biomaterials for applications in biomedical devices and re-
generative medicine. It is anticipated that the gradient approach, and in
particular the 2D orthogonal gradient approach, will be used increasingly in
conjunction with related high-throughput platforms to enhance our
understanding of bio-interfacial phenomena and to rapidly identify optimal
surface conditions for cellular responses such as attachment, proliferation
and differentiation. Once identified, the optimal characteristics can be
scaled up and used in the manufacturing of new and improved biomaterials
and biomedical devices.
With the rapid advancement of regenerative medicine and cell therapy in
recent years, for example advancements in skin regeneration and human
tissue grown in a Petri dish, growth in this field will rely on the effective
isolation and scale up of specific stem cell populations. Additionally, reliable
procedures for the controlled and directed differentiation of stem cells will
be required. The use of 1D, 2D and 3D gradients in conjunction with other
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