Biomedical Engineering Reference
In-Depth Information
Shear stre
ss
Cell-cell
interaction
Soluble factors
and receptor
Stem cell
Cell-ECM
interaction
ECM rigidity
Figure 6.1
The different physical and biological responses encountered by stem cells in their natural
microenvironment.
insoluble factors. In addition, the stem cells also respond to the juxtacrine cells. The extra-
cellular matrix (ECM) molecules present in the niche and the tissue stiffness also influence
the proliferation, migration, and differentiating ability of stem cells [1, 2] (Figure 6.1).
Therefore, it is desirable to use more biomimetic
in vitro
culture conditions to regulate
the different biological processes exhibited by the stem cells. The natural cell environ-
ment, which is tightly controlled at the very small scale, is difficult to provide in cultured
in vitro
conditions, by conventional laboratory techniques in a restricted manner. In this
regard, the emerging technologies in nanoengineering, like nanomechanics, nanofluidics,
nanofabrication, and nanostructured biomaterials, have their own specific potential for
use in stem-cell technology, tissue engineering, and regenerative medicine [3].
For example, complex mechanical interactions are present between each cell, the environ-
ment, and neighboring cells, among which surface traction plays a major role in different
cellular functions that influence cellular adhesion, migration, and differentiation, amongst
other things. Recently, Khetan
et al.
showed that covalently cross-linked hyaluronic acid
(HA) hydrogels, having cell-mediated degradation, show low cell spreading and high traction
inducing differentiation of human mesenchymal stem cells (hMSCs) into the osteogenic
lineage. Whereas, hydrogels having further secondary cross-linkings showed lower degrada-
tion, suppressed traction, and, most importantly, adipogenesis of hMSCs [4]. In this regard,
Ng
et al
. proposed a new gel-mechanics hyperelastic model in a finite element method
concurrently applied with a linear elastic model, which is usually used in the study of trac-
tion-force microscopy [5]. The outcome of their study highlighted that the inimitable
combination of microscopic mechanical characterization along with the Mooney-Rivlin
model and three-dimensional finite-element methods relating to traction-force computation,
may assist in developing a better assay in traction-force microscopy - having better accuracy
and simplicity.
Thus, the developments in nanoengineering tools will help to bridge the gap between
nanoscale level constituting the cytoskeleton, the microscale level containing individual
cells, the mesoscale level containing the extracellular matrix and the macroscale level that
considers the tissue and finally will help to translate the technology from the bench to the
bedside (Figure 6.2).
