Biomimetic Nanofi brous Scaffolds for Bone Tissue Engineering Applications - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 77

a discussion of various modifi cations to the electrospinning apparatus,
see Teo and Ramakrishna [79].
More recently attempts have been made to increase the porosity of
the fi ber mats through either the use of sacrifi cial fi bers [73], or a leach-
able porogen such as sodium chloride [80]. Such techniques succeed in
increasing porosity, which presumably will lead to better cellular infi l-
tration, but only limited studies have been conducted on these methods.
An additional promising technique is referred to as wet spinning—
depositing the spun fi bers into a water bath instead of on a target which
creates a loose, tangled web of fi bers reminiscent of unspun cotton [81].
While lacking in mechanical properties, this material shows promise in
applications such as cartilage defect repair or other applications where the
wound site is completely enclosed and not subjected to load [82].

4.3.2 Biological Behavior of Electrospun Scaffolds

As with self-assembling scaffold designs, few studies have been con-
ducted to determine the biological performance of electrospun scaffolds
in bone TE applications, and even fewer have utilized in vivo testing,
with no studies utilizing a fracture healing model. In general, electros-
pun scaffolds enhanced cellular proliferation and attachment compared
to smooth surfaces [83]. This is likely due to the increased surface area of
the fi ber mats, allowing for increased protein adsorption onto the surface,
and hence increased cell adhesion capability. One study looked at scaf-
folds made of the same PLGA polymer but varied the fi ber diameter from
140-3600 nm and saw decreased cellular proliferation on small diameter
fi bers, and a similar experiment using PGLA fi bers 250 or 2500 nm in
diameter saw a similar effect, an effect attributed to increased cell adhe-
sion [62]. At larger fi ber diameters, cells treat each scaffold fi ber as a fl at
surface, and cellular behavior is indistinct from a fl at surface [62, 84].
Of particular concern to bone tissue engineering is the ability of the
scaffolds to support differentiation into an osteoblast phenotype and for
mineralized tissue formation. The data here is somewhat contradictory,
with most studies fi nding that electrospun scaffolds of various diameters
and materials are able to support differentiation and ECM deposition
[85], but in one instance MC3T3 murine pre-osteoblasts appeared to have
lower alkaline phosphatase (ALP) activity on PCL electrospun scaffolds
than on fl at surfaces [62]. A similar study using mineralized PLLA elec-
trospun scaffolds reported increased ALP activity, possibly indicating that
through better selection of scaffold composition, improvements in cellular
behavior can be obtained [86].
An in vitro experiment from the Vacanti lab utilized electrospun PCL
scaffolds seeded with MSCs for 4 weeks and then implanted in an ectopic
site in a rat model [87]. The scaffolds maintained their shape over 4 weeks