Biomedical Engineering Reference
In-Depth Information
for signal delivery with the aid of an expanded terminal structure called the
growth cone at the end of the axon shaft. The growth cone has some specific
features consisting of filopodia and lamellipodia developed by F-actins and
microtubules. Those cellular cytoskeletons change their spatial organization
inside the growth cone continuously via external cues that mostly originate
from the substratum over which cells adhere by a phenomenon known as
contact guidance. Neuroscientists have also observed that glial cells in the
central nervous system provide natural physical cues to migrating neurons.
Basement membranes, which are a natural substrate for cells in different parts
of the body such as the corneal epithelia, possess a complex, three-dimensional
(3D) topography consisting of nanometer-sized features. The topographic cues
of the ECM play vital roles in cellular behavior, adhesion, spreading,
migration, proliferation and differentiation. Researchers have tried to mimic or
amplify the topographical effects of the cell's native environment by creating
artificial substrata designed with microstructures and nanostructures that
stimulate neurons to grow around such structures.
As mentioned above, the goal of making chemical and topographical
modifications on a substrate material is to enhance biocompatibility as well as
to modulate cell adhesion. In this respect it is crucial to recognize that an
implantable electronic device, for example, will be comprised of different
components made of various materials—electrodes, insulators, encapsulation
materials and so on. Material use will be highly variable ranging across
polymers, glass, indium tin oxide (ITO), metals, silicon, quartz and sapphire.
The main purpose of the rest of this chapter is to review concisely, with an
emphasis on neurons but not restricted to this cell, the various approaches that
have been employed to attempt the retention of biological integrity, healthy
growth and proliferation. The spatial guidance and patterning of neurons on
substrates as it pertains to the formation of networks is also discussed in
Chapter 4.
d
n
4
t
3
n
g
|
0
n
3
.
2.5.2 Bare Substrates
The most straightforward approach has been to simply attempt the intro-
duction and growth of cells on either bare inorganic, surfaces (e.g. plain metals,
silicon) or organic materials such as polymers. Often the aim is a comparison of
bare surfaces with treated substrates in order to investigate possible methods
for enhancing biocompatibility and hemocompatibility (e.g. reduction of
thrombogenicity). We outline some examples here (morphology, physical and
chemical patterning of these substrates is discussed later).
One of the materials heavily employed in devices associated with bioanalysis,
in particular microfluidic and so called 'lab-on-a-chip' structures, is
poly(dimethylsiloxane) (PDMS)
19-21
and polymers belonging to a similar
chemical family. This material is thought to possess advantageous properties in
terms of biocompatibility.
22
The polymer is also low in terms of permeability to
water and displays low electrical conductivity.
23
For these reasons it has been
