Biomedical Engineering Reference
In-Depth Information
The Effect of Nanofibrous Scaffold Parameters
on Stem-Cell Behavior
Since the micro- and nanostructures of the substrate, its stiffness, and biochemical stimuli
determine the behavior of cells seeded on the scaffolds, these parameters are essential to
control during scaffold designing [65].
Biochemical
Self-renewal, phenotype modulation, and differentiation mechanisms of stem cells vary
with respect to the presence and intensity of adhesion ligands, either from the ECM or from
the neighboring cells, as well as the immobilized growth factors [66]. It has been found that
the affinity and density of ligands at the cell-biomaterial interface influence the fate of stem
cells [67]. There are two strategies to improve the interaction of cells and scaffolds. One
approach is based on signaling through the interaction of cell attachment sites and cell sur-
face receptors that regulates cell proliferation. Therefore, the modification of biomaterials
with incorporation of cell-binding peptides that can interact with cell receptors is a simple
way to produce bioactive scaffold materials [68]. The other approach is to perform encapsu-
lation of soluble bioactive signaling molecules within the electrospun scaffold, whereby it
acts as a vehicle for release of growth factors to the cell microenvironment [4, 68]. These two
kinds of biofunctionalization strategies are described in detail later. Another aspect of the
chemical effect of the scaffolds is to obtain an optimal balance of hydrophobic-hydrophilic
forces of the matrix that could dramatically alter the cell-matrix interactions and in turn
has a profound impact on various cellular behaviors, such as cell adhesion, shape, motility,
cytoskeletal organization, and differentiations [69].
Biophysical
The submicron and nanoscale topography can control fundamental cell behavior, including
proliferation, migration, and differentiation. It is important to choose an appropriate topo-
graphically patterned substrate to achieve the desired cell responses because cell responses
vary depending on the cell type, topographic-feature size, geometry, and compliance of the
substrate [70]. The influence of the topographical cues elicited by nanofibrous scaffolds can
be explored at two levels: micro- and nanoscale. Fiber diameter, fiber alignment, pore size,
porosity, and pore interconnectivity are considered as the microscale effective parameters,
while surface roughness is a nanoscale feature that affects the fate of stem cells.
Pore-size affects cell binding, migration, depth of cellular in-growth, cell morphology, and
phenotypic expression [71]. Fibers of different sizes may offer different curvature effects to
the cells. The effect of fiber diameter on cell behavior has been investigated in many studies,
and the results show contrasting effects of fiber diameter on cell adhesion. In addition, fiber
diameter, through control of the pore size, can also affect cell behavior. Furthermore,
differentiation of stem cells from different origins has been explored on nano- and micro-
sized biodegradable polymeric fibers. Another important aspect is fiber alignment, which
guides the orientation of colonized cells. Aligned fibers have been found to promote
organized regeneration of periodontal tissue, myotubes, and primary and secondary neurons
[71]. Studies performed in our laboratory have also shown that the proliferation and
differentiation of nerve stem cells on electrospun aligned fibers were significantly higher
than on randomly distributed fibers [49, 72]. In addition, fiber alignment had an indirect
effect on stem-cell behavior through rendering anisotropic mechanical features to the scaffold
[71], which might be of significance in some tissue-engineering applications.
