Biomedical Engineering Reference
In-Depth Information
in part by scars and a lack of a relevant cellular matrix has led to the investigation of neural tissue
engineering to assist regenerating axons to reconnect the nucleus to points of infl uence.
There are many different approaches to neural tissue engineering, with most involving attempts
at mimicking the natural ECM by fabricating pores, ledges and fi bers so as to present the growing
axons with appropriate cues and a permissive environment. The tip of the regenerating axon or
neurite perceives these cues through a specialized ending known as a growth cone that transduces
the cues into intracellular signals for navigation and tip extension. Conventionally, nanostructured
scaffolds for neural tissue can be manufacture by a variety of methods. One of the new and most
promising techniques involves utilizing electrospinning to fabricate a synthetic EMC from resorb-
able polymeric fi bers.
It may be possible to control neurite outgrowth and cell spreading, adhesion, and proliferation
of
in vitro
cultures by manipulating other topographical features of the scaffold [59]. The orienta-
tion of electrospun scaffolds can also be easily modifi ed by employing different collection devices.
Neurons grown on surfaces with parallel nanoscale ridges form neurites that are aligned with these
ridges [60,61]. Similarly, the direction of neuron growth of neural stem cells (NSC) depends on
fi ber alignment: neurite extension is parallel to the fi ber direction when cultured on aligned PLLA
nanofi brous scaffolds and is random on nonaligned scaffolds. The rate of differentiation into neu-
rons is also dependent on fi ber diameter, with more cells differentiating on aligned nanofi bers than
on randomly oriented microfi bers. The effect of fi ber diameter was also shown on scaffolds with
minimal fi ber alignment. This study supported the idea that nanofi bers enhances differentiation of
the stem cells and neurite extensions, describing axons of up to 100 µm running parallel to aligned
fi bers. The authors attributed this encouraging performance to the enhanced contact guidance of
neurite extensions with nanofi brous scaffolds, providing a positive guidance cue. However, it also
raises many questions. The mechanism that provides directional changes remains unknown and the
cells used in the study were not fully phenotyped as a result of which the relative contribution of cell
type and structure remains unclear.
5.4.5 E
LECTROSPINNING
OF
C
ELLS
A major obstacle in creating TEC based on nanofi bers is a good integration between the cells
and the scaffold. One method of resolving this issue is by electrospinning the cells concurrently
with the nanofi bers. Stankus et al.
[62] coelectrospun SMCs and poly(ester urethane urea) (PEUU)
and obtained well-integrated cell-nanofi ber constructs. The cells were present across the whole
thickness of the constructs and they showed minimal necrosis from the electrospinning process.
Townsend-Nicholson and Jayasinghe [63] reported the possibility of electrospinning cells and
synthetic polymers using a coaxial spinneret method. A two-chambered capillary was used to elec-
trospin a composite thread comprising of an outer poly(dimethylsiloxane) (PDMS) shell and an
inner biosuspension core containing the cells. The cells existed as encapsulated aggregates in the
PDMS thread and showed no impairment of viability due to the electrospinning.
5.5 CONCLUSION
Electrospinning is a relatively inexpensive manufacturing technique for submicron and micron
diameter fi bers from polymer solutions or melts. The process is of interest for scaffold fabrication,
as the resulting fi bers have similar diameters to that of certain ECM microstructures, particularly
the higher ordered collagen microfi brils. The fl exibility of the electrospun fi bers, due to the very
high aspect ratio (length/diameter), is also benefi cial as they allow the seeded cells to remodel their
surroundings. The size of scale is important in this instance; instead of many cells adhering to one
fi ber, one cell may adhere to multiple fi bers.
It is evident that the response of many cells is signifi cantly different when subjected to nano-
and microscale structures and topographies. One line of reasoning for the enhanced response of
