Biomedical Engineering Reference
In-Depth Information
Micro/nano
fluidics
Bio
printing
Micro
stamping
Micro/nano
engineering
Lithography
Nano
electronics
Nano
topography
Figure 6.2
The different micro- and nanoengineering tools used to study and develop stem-cell
engineering.
Nanoengineering to Study Stem-Cell Niche
The microenvironment of a particular stem cell contains other homotypic cells or several dif-
ferent heterotypic cells. Stem-cell communication with other niche cells may be through juxta-
crine interactions mediated either by tight or adherens junctions or by gap junctions, or they
may interact by paracrine or autocrine signaling pathways, including the Notch, Wingless
(Wnt), Sonic hedgehog (Shh), and Smad pathways [6]: these cell-cell interactions help to
restrict the stem cells within a definite space and they also decide the fate of stem cells.
The conventional approach for studying homotypic cell interaction is by seeding different
densities of cells in a culture dish and studying the effect on the biological behavior of the
cells; for studying heterotypic cell interaction, co-culture of different cells can be the chosen
option, but this cannot consider the particular signaling molecules produced by the niche cells
in a spatial environment. Study of cellular interaction in a three-dimensional environment is a
great challenge. In this regard, micro- or nanofabrication-based approaches, like microstamps,
microstensils, or bioprinting, can be useful as they can accurately control, move, and arrange
cells in three-dimensional space so as to control cell-cell contact [7, 8].
For example, microstamps are devices that permit seeding of each cell type in a sequential
manner in predefined patterns. Microstamps are fabricated by polymerizing polydimethylsi-
loxane (PDMS) in a micro-electro-mechanical systems (MEMS) technology based on a
finely etched mold that provides the substrate for growth of different cell types. Cell-cell
interaction, including heterotypic cell interaction, can also be studied by using laminar flow
in micro- or nanofluidic devices, wherein, stem cells are immobilized on engineered 'capture-
cups' and laminar flow is used for flowing other cell types over it, in which the interacting
cells become captured [9]. Bioprinting also can be used to produce spatially oriented co-
culture by stamping with precise gaps different bioactive molecules layer-by-layer [10].
Bioprinting is a rapid way in which computer-aided tools help create three-dimensional
structures by localized deposition of several types of cells and biomaterials, and the result-
ing structure can mimic the three-dimensional cellular microenvironments by having the
usual physiological, mechanical, and regulatory cues.
