DESIGNING NANOFIBROUS SCAFFOLDS FOR TISSUE ENGINEERING - Advanced Biomaterials: Fundamentals, Processing, and Applications - page 434

phenotype when cultured on a 3D scaffold, but dedifferentiate to a fi broblastic
cell type when cultured on a 2D substrate [25]. This provides a rationale for fab-
rication of scaffolds with 3D architecture, adequate porosity, and interconnectiv-
ity of pores. A potential constraint of using a 3D scaffold could be limited diffusion
of nutrients and gases [26]. This can potentially be overcome by providing dynamic
culture conditions to cells. Use of bioreactors can provide physiological levels of
nutrient media transport, and mechanical stimuli for improved cell growth during
construct development [26,27].
13.2.2.1 Infl uence of Nanometer Scale Features of Scaffolds in Tissue
Engineering. The topography of the scaffolding surface plays an important role
in terms of cell behavior [28]. Previous studies have already demonstrated the
response of cells to micrometer range topographies such as grooves/ridges [29,30]
and their ability to distinguish between different topographies [31]. The fi bers
present in the ECM and basal lamina possess diameter in the nanometer scale.
One of the approaches for scaffold design is a biomimetic approach wherein the
incorporation of nanoscale features in the scaffold architecture provide for close-
ness to the native environment [32]. It has been demonstrated that nanoscale
features support better cell growth/response as compared to microscale surface
features [33,34]. In connective tissue, the structural protein fi bers, such as colla-
gen, are the building blocks of natural ECM and they have a hierarchical struc-
ture with the fi ber diameters ranging from 50-500nm [35]. Since cells are
accustomed to nanometer scale topographies present in the native ECM, the
design strategies of scaffolds have recently involved mimicking these nanoscale
features of ECM component [36].
Several studies have demonstrated that incorporation of nanoscale features
in the scaffold elicit diverse cell behavior, ranging from changes in cell adhesion,
cell motility, cell orientation to surface arrangement of cytoskeleton components
[37,38]. The changes are even seen at the transcriptional level, as there is modula-
tion in the intracellular signaling pathways that regulate cell activity and gene
expression [39,40]. There is always an exchange of information between ECM,
cytoskeleton and nucleus. Soluble mediators bind to integrin receptors on the cell
surface which in turn stimulates the receptor mediated signaling, including the
activation of kinase pathway, lipid pathway and specifi cally Rho GTPases, Rho,
Rac, and Cdc42 [37,41]. Studies conducted in the past have demonstrated that the
cells retained their morphology and shape on nanofi ber matrices and there was a
comparative increase in the production of ECM components by the cells [39,42].
Thus, for tissue engineering, the need is to mimic the native ECM at nanoscale in
order to recapitulate the organization and function of native tissue.
13.3 METHODS OF NANOFIBROUS SCAFFOLD SYNTHESIS
Several novel fabrication techniques have been developed to process biodegrad-
able and bioresorbable materials into 3D polymeric scaffolds [43]. Fiber bonding