Biomedical Engineering Reference
In-Depth Information
study of biocompatibility by randomly distributed but spaced RGD moieties.
There was no attempt to orchestrate ordered patterns with respect to peptide
spacing as mentioned above.
In contrast, Gooding and colleagues
50
have specifically pinpointed the fact
that etching of silicon, normally used to produce electronic devices, can be
utilized to provide combined topography and RGD presentation to cells. Wet
chemical etching of silicon with potassium hydroxide was employed to produce
random pyramidal structures on both the nano- and micro-scale of the semi-
conductor surface. Following removal of the oxide layer the silicon wafers were
subjected to the hydrosilylation process to produce monolayers. Using
standard surface chemistry the peptide, Gly-Arg-Gly-Asp-Ser, was attached to
the surface in various densities of surface population (6
10
2
to 6
10
11
RGD
mm
2
). This surface was then allowed to interact with fluorescent-labeled
bovine endothelial cells. Interestingly it was found that the flat or nanoscaled
surface adhered more cells than was the case for rougher surfaces. Cell
spreading was controlled more by the population density of the peptide than by
substrate morphology. The important conclusion was reached that initial
contact of cells with a substrate may be controlled by the topography whereas
the engagement of cell surface receptors is dominated by the surface chemistry,
i.e. RGD surface density.
In the context of the results outlined above, Gooding and colleagues
51
had
previously commented on how cells migrate on the micro- and nanoscale with
particular reverence to oncology. In this earlier paper they reviewed the stages
of cell migration subsequent to receiving ECM cues—polarization, protrusion,
traction and disassembly. These processes can be instigated by various chemical
signals, such as hormones and growth factors, where the spatial chemistry of
ligand binding to cellular receptors is critical. The possibility of fabricating
microfluidic systems (see Chapter 4) and of incorporating nanostructures on
surfaces offers great potential for examining how cells begin the migration
process. This is important in biological processes such as metastasis.
Given the success of patterning both by nano-gold particles and silicon
nanofabrication protocols, it appears that the recent silanization adlayer
chemistry introduced by Thompson et al.
52
and described briefly in Chapter 1,
offers an attractive alternative to hydrosilylation. In this case covalent bonds to
-OH groups on a variety of surfaces via simple trichlorosilane reactions could
clearly be applicable to SiO
2
and, therefore, patterning. The material advantage
over other systems is that the adlayer yields highly biocompatible substrates in
addition to the basic requirement for the possibility to attach orchestrated
patterns of peptide and such ligands.
53
The technology was developed with
biosensor devices in mind, but the avoidance of surface protein adsorption also
offers possibilities with respect to biocompatibility in biological fluids.
d
n
4
t
3
n
g
|
0
n
3
.
2.5.5 Substrate Morphology
In the previous section we referred to research on the influence of surface-
attached RGD and patterned peptide spacing on cell-surface behavior.
