Biomedical Engineering Reference
In-Depth Information
fibrosis, and myocardium. Mauck and co-workers recapitulated the complex tissue
organization and mechanical properties of the annulus fibrosus with anisotropic,
nanofibrous laminates seeded with mesenchymal stem cells [56]. The scaffolds
approached the mechanical properties of native tissues after 10 weeks of culture.
Modification of the surface of the fibers with precipitated bioapatite can also lead
to dramatic increases in scaffold stiffness [57].
The mechanical properties of scaffolds can have strong impacts on cell prolif-
eration and stem cell differentiation. Discher and co-workers demonstrated that
the commitment of stem cells to a particular phenotype was highly dependent
on the stiffness of substrate [58]. The most compliant surfaces were neurogenic
while the stiffest matrices were osteogenic. Ingber and co-workers demonstrated
that cell phenotypes could be affected by cellular adhesion to the ECM and the
mechanical tension in cytoskeleton [59]. In general, rigid substrates tend to pro-
mote cell spreading by resisting cell tension [60]. Rigid substrates supporting
higher levels of isometric tension in the cell allow spreading and growth of cells
such as fibroblasts and endothelial cells. Flexible substrates that cannot withstand
stretching will result in retracting, rounding up, and the down regulation of genes
associated with proliferation [61]. Controlling the mechanical properties of both
bulk and individual nanofibers will help optimize scaffolds for tissue regeneration
by recapitulating the properties of the tissue being replaced and by providing the
appropriate cues for the seeded cells.
9.2.6
Cell Infiltration
The porosity of a nanofiber scaffold can directly affect the infiltration of cells [62].
Although many research groups have focused on the development of fibers with
reduced diameters to increase the specific surface area for loading of bioactive
molecules, it has been shown that the scaffolds consisting of thinner fibers tend to
have a lower porosity due to a denser packing of the fibers [63]. One technique for
increasing the porosity of a scaffold is based on salt leaching. The setup for this
technique is identical to that of electrospinning with a co-axial spinneret (Figure 9.2,
top left). The nanofibers produced using this technique had a core-sheath structure
with the polymer as the core and crystals of the salt in the sheath. The high
voltage was able to stretch the jet of polymer solution into a nanofiber while the
salt crystals were formed and attached to the surface. The salt crystals were then
dissolved in water to generate a mat with high porosity, which could facilitate cell
infiltration up to 4mm in depth [64]. Other approaches include selective removal
of sacrificial fibers in a scaffold prepared using a dual spinneret system [24]. To this
end, Mauck and co-workers co-electrospun PCL and PEO (a water-soluble polymer)
from two separate spinnerets to form a dual-polymer scaffold (Figure 9.2, bottom
left). The PEO fibers were dissolved gradually in the cell culture medium and cells
were found to be present throughout the entire scaffold [24c]. Although these two
methods could considerably improve cell infiltration, they also led to compromised
structural integrity and macroscopic delamination. Recently, Jun and co-workers
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