Biomimetic Nanofi brous Scaffolds for Bone Tissue Engineering Applications - Biomimetics: Advancing Nanobiomaterials and Tissue Engineering - page 82

A fi nding from one of the above experiments suggested that cells are
capable of binding directly to the scaffold nanofi bers. Adding dehydropro-
line, an inhibitor of type I collagen fi bril formation, to the culture reduced by
90% the expression of the a 2 integrin subunit on smooth-walled scaffolds,
but showed little change in a 2 expression on the nanofi brous scaffolds [108].
Expression of BSP and OCN, late markers of bone formation, were likewise
affected—nearly eliminated in smooth-walled scaffolds, but continued to
be expressed, albeit at a lower level, on nanofi brous scaffolds. In essence
it appeared that the nanofi brous scaffolds were emulating a collagenous
surface to the degree that cells were expressing collagen-specifi c integrins
while cell-secreted collagen fi ber assembly was blocked. It was hypothe-
sized that the a 2 b 1 integrin was somehow attaching directly to the scaffold
nanofi bers, possibly due to the helical structure of PLLA crystals which are
similar in dimension and shape to the helical structure of collagen.
Techniques for increasing the bioactivity of TIPS nanofi brous scaffolds
include addition of bioactive materials and the inclusion of growth factors
or other drugs. Gelatin microspheres can be used as the sacrifi cial poro-
gen, and during processing gelatin is transferred to the polymer matrix,
obviating the need for an additional coating step. Cells cultured for 24 h
on the gelatin-coated scaffolds exhibited a more spread morphology,
and the amount of ECM deposited after 2 weeks culture was increased
compared to uncoated scaffolds [109]. Hydroxyapatite also can be either
incorporated into the polymer solution before scaffold fabrication, or
precipitated onto the scaffold post-fabrication [110, 111]. HA containing
nanofi brous scaffolds demonstrated increased bioactivity and osteogenic
behavior in vitro .
Both solid-walled scaffolds [112], and nanofi brous scaffolds can be used
to deliver growth factors or other drugs [113, 114]. A common approach
to controlling drug elution out of scaffolds is the incorporation of micro-
or nanospheres containing the drug molecule. Techniques have been
developed to both embed nanospheres in PLLA matrix during fabrica-
tion as well as attaching them to the exposed surfaces of an already fabri-
cated nanofi brous scaffold [114, 115]. While embedding the nanospheres
directly is simpler, the surrounding polymer matrix affects sphere erosion
and drug elution, and it is more diffi cult to precisely tailor the rate of drug
delivery. Attaching nanospheres to a scaffold pore surface is more promis-
ing as it allows for precise control of drug elution kinetics independent of
any scaffold properties. Other bioactive molecules have also been success-
fully incorporated into nanosphere-loaded TIPS scaffolds [113, 116].
4.4.3 Conclusions
Overall thermally inducible phase separation is a very useful and
straightforward means of fabricating nanofi brous polymeric materials.