141that bioactive NGF sustained release for 3 months from the matrix, using a PC12
neurite outgrowth assay to confi rm bioactivity of NGF [ 286 ]. Based on these data
and others [ 284 – 286 , 290 ], these electrospun nanomaterials may be ideal for growth
factor and therapeutic drug localization.
The degradation of nanofi ber matrices and subsequent release profi les have alsobeen investigated as a function of local pathological pH environments. This
approach allows for development of stimuli-responsive nanofi bers, which, in turn,
broadens their clinical relevance. In vitro studies on the release profi le of pH-
responsive electrospun nanofi bers demonstrated that total amount of drug release
was accelerated due to both the pH-induced structural and morphological changes
of the drug- fi ber complex and to degradation of the matrix polymers themselves
[ 291 , 292 ]. Additionally, modulating concentration of acid-labile polymer seg-
ments allows for further control over the burst release profi le. Yuan et al. designed
and produced an acid-responsive ibuprofen-loaded PLA fi brous scaffold doped
with sodium bicarbonate to ameliorate the infl ammatory response and promote
regeneration. They reported reductions in gene expression of IL-6 and TNFα and
increased expression of VEGF in a muscle wound. Given the critical roles of IL-6,
TNFα, and VEGF in CNS injury pathology, the development of a similar system to
treat CNS injury would be of interest to the fi eld of neuroregeneration [ 293 ].
Further, results showed that the ibuprofen-loaded PLA fi brous scaffold attenuated
the infl ammatory response more effectively than no-drug and non-acid responsive
controls [ 293 ].
7.6.3 Microparticles and Nanoparticles for Neuroregeneration
Nanoparticles ( NPs) and microparticles (MPs) are colloidal submicron to micron
sized polymeric particles, often with a therapeutic agent of interest encapsulated
within the polymeric matrix or adsorbed or conjugated onto the surface of the struc-
ture [ 294 , 295 ]. Traditionally, both NPs and MPs have been synthesized using tech-
niques like emulsifi cation, electrospraying, and microfl uidics [ 296 ]. Although some
authors reserve the term “nanoparticle” for specifi c size cut offs, for the purpose of
this review, the terms “nanoparticle” and “microparticle” refer to particles where
the dimensions of the particle are measured in nanometers and micrometers,
respectively.
There have been a number of studies validating the effi cacy of drug or bioactivemolecule delivery in both the brain and spinal cord using biodegradable NPs (e.g.
poly(lactide-co-glycolide) (PLGA and PLAs) and liposomes. PLGA and PLA are
polyesters, which undergo hydrolysis upon implantation into the body, forming
biologically compatible and easily metabolized moieties [ 297 , 298 ]. Drug
entrapped in PLGA and PLA is released at a sustained rate via diffusion of the drug
in the polymer matrix and by degradation of the matrix itself [ 297 ]. In these sys-
tems, the rate of degradation can be modulated by either changing block co-poly-
mer composition or molecular weight, which alters the release of encapsulated
7 Regenerative Strategies for the Central Nervous System