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increased OPC generation, enhanced survival of dopaminergic neuronal cul-
tures, and protection from toxicity [ 213 ]. In stroke models, delayed administra-
tion of FGF-2 has been shown to decrease infarct volume and increase functional
recovery in rats [ 37 , 38 ]. Despite its benefits, FGF2 administration poses in vivo
limitations. For example, while FGF-2 induced axon myelination in periven-
tricular white matter, it also resulted in significant loss of oligodendrocytes at
later time points in both healthy and PD brain models [ 211 , 214 ]. Further, a
significant decrease of myelination in the caudal anterior medullary velum has
been reported as an effect of FGF-2 delivery to rat pups [ 43 ]. These data sug-
gest that FGF2 has a dual effect on neural environment , both providing neuro-
protection to endogenous cells and potentially limiting remyelination and
oligodendrocyte survival. Therefore, investigations into parameters that may
modulate FGF2 efficacy could inform the design of more precise FGF2 delivery
paradigms.
7.6 Biomaterials to Enhance Neuroregeneration
In order to circumvent the barriers of therapeutic administration (e.g. BBB/BSCB
permeability) and minimize invasive therapeutic delivery paradigms, researchers
have turned to engineered biomaterials constructed from synthetic or natural mate-
rials. These techniques benefi t the CNS immensely by providing increasingly effi -
cient avenues for delivery of therapeutics for brain and spinal injury/disease
pathologies.
There are three major requirements that a biomaterial must meet in order to besuitable in this regard. First, the mechanical properties of the biomaterial must be
robust enough to sustain local fi xation (specifi cally in the spinal cord), yet com-
pliant enough so as not to compress the local tissue [ 215 – 217 ]. Second, the bio-
material must be suffi ciently biocompatible so as to integrate with the local
environment (i.e. appropriate porosity, permeability, and surface nanotopogra-
phy) [ 216 , 218 ]. Third, the material must degrade at a suitable rate, similar to that
of the ingrowth of support tissue and the extension of extending axonal processes
[ 216 , 219 ]. Many different types of materials have been used to develop scaffolds
for neuroregeneration including natural materials like hyaluronic acid (HA), col-
lagen, chitosan, agarose, alginate, and more; synthetic materials, such as nitrocel-
lulose membranes, synthetic polymers, and biodegradable synthetic polymers;
and biological grafts, such as fetal tissue (brain and spinal cord) and peripheral
nerve implants [ 215 , 219 – 222 ].
While the great number of biomaterials currently in use experimentally seems tobe individually idiosyncratic, they can be generalized into three categories: hydro-
gels, nanofi bers, and micro/nano particles [ 220 ].
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