Page 56 - IJB-9-3

International Journal of Bioprinting Curved cell-guided structures printed by FDM

the actual interactions are far more complicated. Cellular 200 and 400 nm. Fibers with 50–2000 nm in diameter can
interactions include not only mechanical forces but a series influence the migration speed of mouse mesenchymal stem
of signal transformations [47,48] . cells, and the maximum migration speed was observed
[58]
Moreover, recent research showed that cells tend with the fibers with 800 nm diameter .
to leave long-lived physicochemical footprints along Interestingly, the cells are mainly directed by one of
their migration trajectories, which can alter the path of the curvatures when two different scales of curvature
themselves and other cells . This phenomenon should guide the cells simultaneously. Research has shown
[49]
be transformed into a mathematical description and that mesoscale curvature can overrule the influence of
considered in a model in the future. Besides, the cells were nanoscale curvature . Cell alignment and migration were
[59]
regarded as a circle in this model, which did not correspond governed by the nano-scale fibers (diameter: 100–200 nm)
to spindle cells in the experiment and caused inaccuracy when the curvatures of the cylindrical surfaces were low
between the experiment and the simulation. (diameter > 1000 µm), and the cells increasingly aligned
and migrated along the axis of the cylindrical surface as
4.4. Effect of curvature ranging from nano-scale to the surface diameter decreased (diameter: 250–1000 µm).
milli-scale on the cells
Curvatures can influence the cell’s behavior on the 5. Conclusion
nanometer to the millimeter scale. The curved structures
at the supracellular scale only directly affect the cells near In this study, channels with customized curvature and width
the curved pattern and indirectly impact the farther cells were printed using a two-stage temperature-controlled
via cell–cell interactions . Subcellular or cellular-scale FDM method, and the effect of millimeter-scale curvature
[50]
curvature can directly contact and impact the cells . of curved channels on the proliferation, morphology,
[5]
orientation, and migration of M-22 cells was systematically
Supracellular curvature can affect the cell’s behavior, investigated in vitro. The experimental results indicated that
especially in cell migration. Myoblasts migrated parallel the cells significantly changed their morphology and aligned
to the longitudinal direction of the hemicylinder-shaped along with the curved channels; the proliferation, single-cell,
non-planar surfaces with diameters of 3–50 mm, and and front-end speed of collective cells were all increased on
cell differentiation and orientation were also augmented these curved structures, compared with the straight and
on the surfaces . In this study, we investigated the unstructured counterparts. Moreover, the migration of
[11]
effect of curved channels with radii of 1.5–3 mm on cell cells in curved channels with varying widths and radii was
proliferation, morphology, orientation, and migration, numerically simulated, with the results showing that the
with the results showing that the curvature can influence channel width and relative size of the cells could influence
the aforementioned cell behaviors in this range. The their response to curvature. Our simulation results also
curvature slightly larger than cells (tens to hundreds of demonstrated the mechanism involved, i.e., curved channels
microns) can facilitate the alignment of cells [51,52] and can affect the cell–boundary interaction force and the
change the migration trajectories and speed [53,54] . number of valid pseudopodia to regulate the cell behavior.
Curvatures at the cellular scale (a few microns to a Our findings proved that the cells could sense and respond
dozen microns) can impact cell behavior, particularly can to planar millimeter-scale curvatures and revealed the
directly change the morphology and distribution of the underlying mechanism of this phenomenon. To the best of
cells. Cells avoided convex regions when migrating, and our knowledge, this is the first time that the effect of planar
positioned themselves in concave valleys (radius: 1–30 μm, milli-scale curvature on the cells has been explored. It
period: 10, 30, and 100 μm) . Similar research showed provides a practical and straightforward way to manipulate
[55]
that the convex regions (radius: 10 µm, period: 100 µm) cell behavior with millimeter-scale features rather than
acted as topographical barriers to control the organization manufacturing expensive and complex micro-and nano-
of the actin cytoskeleton and nuclei, as well as the collective patterns. The finding mentioned above, wherein milli-scale
migration and orientation of cells . curvature can promote the proliferation, orientation, and
[56]
migration speed of cells, can be applied to the design of
Subcellular scale curves mainly regulate the spreading tissue scaffolds and facilitate tissue repair in the future.
area, orientation, and migration speed of cells. Grooved
substrates with radii ranging from 10 to 400 nm can increase Acknowledgments
the spreading area of the mouse embryonic fibroblasts, but
reduce their polarization (aspect ratio) when the radius We would like to thank Professor Po-Jen Shih of National
increased to 200 nm . Only weak impact was put on the Taiwan University for answering our questions on the
[57]
cell spreading area and polarization when the radius was computational model of cell migration.

Volume 9 Issue 3 (2023) 48 https://doi.org/10.18063/ijb.681