Biomedical Engineering Reference
In-Depth Information
Furthermore, studies of the kinetics of cell-cell interaction have become possible by
using a combination of microfluidics and microfabrication technology. In this regard,
micromachined movable silicon parts have been used for the dynamic regulation of cell-
cell interactions by manipulating the adherent cells within micrometer-scale precision [11].
In addition, dielectrophoresis can help to confine spatially live cells with the aid of an
electrical current. Thus, nanoengineering tools have made it possible to answer many diffi-
cult questions associated with stem cells by the precise control of cell-cell interaction, both
temporally and spatially.
Nanoengineering to Study Stem-Cell Homing
Among the different inherent ability of the stem cells, the homing property of these cells
towards any inflammation site has been highlighted in the clinical world for the potential to
locate any inflammation that may be a tumor site, and to be able to treat that. The homing of
stem cells involves cues by cytokines and, chemokines that form a gradient in the blood stream.
Different conventional approaches have been in use to study cell migration under flow condi-
tions. However, the spatial heterogeneity of fluids found
in vivo
and also the concentration and
gradient of a substance are hard to maintain with the conventional approaches.
In this regard, micro- or nanofluidic devices can produce temporally controlled, extremely
precise spatial gradients of different chemical substances [12]. Microfluidic channels made
of PDMS can be used wherein each channel can be filled manually [13]. These microchan-
nels can be removed or left over the cell layer to further study the behavior of the cells under
fluidic conditions. Different nanoscale chemical substances or proteins can be sent with
properly regulated mixing to specific parts of the cell. Although the new approaches help to
build static or low-flow settings to reduce shear stress, there is still further need of complex
microfluidics circuitry as present innovations are limited to producing gradients for only
few hours or a day [14]. Nevertheless, nanoengineered tools to create stable gradients for a
prolonged time still require exploration.
Mechanical shear stress is a prominent factor that plays an important role during the
migration of stem cells. To reduce this, variation in substrate stiffness can be achieved by
using collagen-coated polyacrylamide gels, wherein stiffness can be modified by varying
the concentration of bisacrylamide cross-linkers [15]. However, in order to recapitulate the
three-dimensional microenvironment it will be essential to develop a technology that will
construct cell adhesive substrates with changeable spatial architecture and with control-
lable local variations, and not be limited to a single stiffness change. Microfluidics-based
lithography techniques allow fabrication of three-dimensional gels in microchannels to
mold multiple three-dimensional gels aligned with each other.
Nanoscale Approaches to Elucidate Stem-Cell and ECM Interaction
In a stem cell niche, the stem cells are embedded in an ECM that is made up of fibers, pro-
teins, collagens, etc., and contains several soluble and insoluble factors that affect the
growth, proliferation, and maintenance of the stem-cell behavior. Furthermore, the ECM
proteins, like collagen I, collagen IV, fibronectin, and laminin, can influence stem-cell fate
and differentiation. For example, Cooper-White and co-workers have revealed that there is
a prime role for ECM proteins and substrate elasticity in regulating the myogenic or
osteogenic differentiation of hMSCs [16].
