Biomedical Engineering Reference
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developed a semi-spherical bowl with small needles randomly distributed on the
inner surface to fabricate cotton-ball-like, uncompressed scaffolds of electrospun
nanofibers (Figure 9.2, bottom right) [25]. This type of scaffold has very high
porosity and encourages inward cell migration. The major limitation of this type of
scaffold is the difficulty of transferring it to other substrates without destroying its
hierarchal structure.
Although many efforts have been devoted to increasing the infiltration of cells
into a nanofibrous constructs, a robust and transferrable scaffold has yet to be
developed and remains a major goal of future work.
9.3
Controlling the Alignment of Nanofibers
In many applications, it is desirable to have a scaffold made of aligned nanofibers,
as the anisotropy in topography and structure can greatly affect not only the
mechanical properties but also cell adhesion, proliferation, and alignment. Aligned
fibrous scaffolds may thus be useful in replicating the ECM for a specific tissue
type such as tendon, where collagen fibrils are aligned parallel to each other. To
this end, Ouyang and co-workers studied human tendon stem/progenitor cells
(hTSPCs) cultured on scaffolds made of aligned or random PLLA nanofibers.
Tendon-specific genes were up-regulated in hTSPCs cultured on the aligned
nanofibers compared to those on the random fibers [18]. Another example is
cardiac tissue, where the ventricular myocardium is composed of perpendicularly
interwoven collagen stripes. This unique anisotropy in cardiac tissue gives rise to its
special directionally dependent electrical and mechanical properties. Entcheva and
co-workers showed that primary cardiomyocytes cultured on a scaffold of aligned
PLLA nanofibers developedmature contractile machinery (sarcomeres). Excitability
of the engineered constructs was confirmed by optical imaging of electrical activity
using voltage-sensitive dyes [17].
Besides mimicking the ECM, the alignment of electrospun nanofibers in a
scaffold can also guide the migration and extension of cells. For example, aligned
electrospun nanofibers have been used to guide the neuronal growth from neural
stem cells (NSCs). Ramakrishna and co-workers have shown that axons of up to
100
m were formed on aligned fibers, which could be attributed to the enhanced
contact guidance [65]. We have also demonstrated that electrospun nanofibers with
a uniaxial alignment could induce the differentiation of mouse embryonic stem
cells (ESCs) into neural lineages with less possibility of scar tissue formation [66].
The alignment associated with the fibers can also accelerate the rate of wound
closure. This is because the alignment confines the migratory route of the cells to a
certain direction so that a shorter time will be needed for cells cultured on aligned
nanofibers to cover the same area comparing with those cultured on random
nanofibers [67]. As a demonstration, we have recently shown that dural fibroblasts
could cover the entire scaffold with a radial alignment at a faster speed relative to a
scaffold made of random nanofibers [68].
μ
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