14 0
can be controlled in the production process and have been shown to have signifi cant
impacts on cell fate [ 275 – 277 ]. For example, one study found that compared to
microfi ber polylactic acid (PLA) scaffolds, nanofi ber PLA scaffolds signifi cantly
increased neuronal differentiation of NPSCs [ 278 ]. Further studies demonstrated
that NPSCs will selectively differentiate into oligodendrocytes on ~300 nm fi bers,
while displaying neuronal phenotypes on ~750 nm fi bers [ 279 ]. Moreover, pattern-
ing, such as grooved substrates, increased cell alignment and neuronal differentia-
tion of rat hippocampal progenitor cells as compared to randomly oriented scaffolds
[ 271 ]. Consistent with these fi ndings, it was later shown that nanoscale ridge/
groove pattern arrays can effectively induce differentiation of hESCs and NPSCs
into neuronal phenotypes without the addition of any biochemical or biological
agents [ 278 , 280 ].
Electrospun polymer nanofi bers have also been shown to be useful in drug deliv-ery applications [ 281 ]. Many therapeutic compounds can be easily incorporated
into the electrospun polymers via the electrospinning process, which unlike com-
mon encapsulation techniques (discussed in the next section) does not require a
complex preparation. There are two attractive properties of the electrospinning
technique with respect to drug/bioactive material loading: (1) the molecular struc-
ture and bioactivity of the incorporated drugs/bioactive molecules are well main-
tained due to the mild processing conditions and (2) the burst release of drugs
in vitro is greatly reduced. The drug release profi le can be tailored to be rapid,
immediate, delayed, or modifi ed dissolution by changing the polymer carrier used
[ 282 ]. Release systems are designed via two electrospinning methods. The fi rst
method for encapsulating drugs is via electrospinning core-shell structures: two
miscible or immiscible components can be spun into a composite fi ber with a core
layer encapsulated inside a shell [ 283 ]. Drugs or bioactive materials encapsulated
using this technique show steady release characteristics, sustaining relatively con-
stant release up to 140 h with tunable initial release profi les [ 284 , 285 ]. One in vitro
release study indicated that threads made from the core-shell fi bers could suppress
the initial burst release and provide a sustained drug release profi le that would be
useful for administering growth factor or other therapeutic drugs [ 284 ]. Another
group used emulsion electrospinning to develop a core-shell structure from ultrafi ne
fi bers of bovine serum albumin and poly(DL)-lactide that allowed for control over
burst release profi les of bioactive protein, extending release to 3 months [ 286 ].
The second method is to mix both the drug(s) and polymer(s) together and per-form the electrospinning process as normal, such that the drugs are embedded
within the entanglement of fi bers themselves. Using this method, drugs can be eas-
ily located on the surface of the fi bers, resulting in a burst effect in the initial stage
of drug release [ 287 , 288 ]. To control drug release profi les, properties such as fi ber
diameter and drug loading can be modulated to yield either longer or shorter periods
of specifi c release profi les. For example, increasing fi ber diameter results in longer
periods of zero order release, and higher amounts of encapsulated drug will result in
a more signifi cant burst release profi le [ 289 ]. Chew et al. successfully stabilized
human β-nerve growth factor (NGF) in an electrospun copolymer of g-caprolactone
and ethyl ethylene phosphate with BSA as a carrier protein [ 286 ]. They reported
A. Roussas et al.