Biomaterials and the Central Nervous System: Neurosurgical Applications of Materials Science - Biomaterials Science: An Integrated Clinical and Engineering Approach - page 142

of these materials, rather than intrinsic properties of the materials, that
make them less biocompatible [37]. These results taken together suggest that
implantation of slowly degrading or nondegradable PEG-based hydrogels
may be well tolerated in humans.
The relative static nature of these types of hydrogels suggests that they
may not be useful in all CNS clinical applications. There may be situations
in which a specific hydrogel's mechanical properties change over time. For
example, amphiphilic diblock copolypeptide hydrogels (DCHs) are syn-
thetic materials whose mechanical properties may be altered by altering
the polypeptide backbone to gain certain functionality [12]. Specifically,
this polypeptide may be altered to impart enzymatic degradability, cell-cell
adhesion, and molecular signaling. Furthermore, DCHs may be thinned
and deformed to allow for injection through a small-bore cannula; follow-
ing injection, these are rapidly reassembled into rigid gel networks [12]
(Figure 6.4). This property allows for their minimally invasive deployment
into the CNS. Investigators have also shown the DCHs induce little inflam-
matory response, glial scarring, or neurotoxicity in the CNS host tissue com-
pared with saline injection controls, suggesting that this material may be
both a safe and versatile tissue scaffold for nerve regeneration.
Recent work on determining the role of matrix stiffness in promoting neu-
rite and axon outgrowth reveals that soft materials appear to be more suc-
cessful in promoting tissue growth in the CNS compared with materials to
higher stiffness [39]. Fibrin gels, composed of fibrinogen and thrombin (the
final two factors in the coagulation cascade), have been shown to support the
growth of cells in vitro and in vivo . Some have suggested that fibrin in par-
ticular is useful in supporting neuronal regrowth because it does not sup-
port glial proliferation [39]. The fibrin gel's preferential support of neuronal
cell ingrowth is thought to result from the different ways neurons and glia
respond to matrix stiffness and from the fibrin gel's low elastic modulus,
which promotes neuronal differentiation [39, 40]. Several groups have shown
that the neurons appear to prefer to grow on soft surfaces and that the in vitro
work utilizing soft materials such as fibrin gels holds promise for future in
vivo work [39-41].
Microelectrode Systems
Much of the current understanding of systems neuroscience, that is, the study
of neural networks and circuits, has developed with the help of implant-
able microelectrode technology, which allows for recording and stimula-
tion of a single neuron or a group of neurons. It is this understanding that
has informed the development of deep brain stimulator (DBS) technology.
DBSs are stimulating electrodes implanted traditionally into the subtha-
lamic nucleus, where stimulating signals are thought to feed into basal gan-
glia circuitry and override some of the motor symptoms associated with
conditions such as Parkinson's disease [42]. Other deep brain targets, such