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

most oriented at R2. Also, a computational model was respectively. The above findings suggested that channel
employed to explore the mechanism of the experimental width was a crucial factor affecting the cellular response
phenomenon. The results showed that the curvature effect to the same curvature. Similar research that cultured cells
on the cells was mainly caused by the influence of the cell– on circular annulus grooves with 100, 150, and 200 µm
boundary interaction forces and the invalid number of in width confirmed this concept, and showed that the
pseudopods generated by the cells. narrower the channels, the cells were more aligned along
the channels . However, a study concluded that the
[13]
4.1. The interplay between proliferation, shape, and MC3T3-E1 cells oriented at curved channels with 50,
migration of cells 100, 150, and 200 μm in radii only due to the width of the
It should be noted that the changes in cell morphology and induction channel, but independent of curvature . In
[42]
single-cell migration speed under the influence of curvature our experiments and simulations, a significant difference
were relevant. Previous studies and our time-lapse between the curved and straight channels was not observed
videos (Videoclips S1–3) proved that cells extend their until the width of the channel was ten times (200 μm) the
lamellipodia while migrating . When a cell extends its width of cells, which indicated that the millimeter-scale
[40]
lamellipodia, the cell body lays flat, causing the aspect ratio curvature could influence the behaviors of cells within a
to decrease. In addition, the morphology was also related specific range of channel width.
to cell proliferation. After analyzing the videos (Videoclips
S1–3), we discovered that the cytoplasm shrinks inward The possible reason for this effect is that the proportion
first, and the cell takes on a spherical shape before dividing. of cells directly in contact with the curved channel is
Other studies also confirmed the transformation of cell various, and a greater fraction of cells interact directly with
morphology in the proliferation process . The faster the the curved channel wall in the narrower channel. Some
[41]
proliferation and migration speed, the higher the probability studies proposed the entropy effect of lateral confinement,
of staining the dividing and migrating cells. which contained the entropy of mixing between packets
of unbound and bound stress fiber proteins with sites
In addition, although the trend of the front-end speed for bound proteins, and the entropy of mixing between
of collective cells with channel curvature coincided with unbound proteins and lattice sites, to explain why cells
single-cell migration speed, the magnitude of the front- behave differently on the channel with different width .
[43]
end speed of collective cells was lower than the single-cell In our experiment, stress fibers evolve between bound and
migration speed in all groups. The stochastic cell migration unbound states in the process of cell migration; therefore,
direction could explain the results; namely, cells will move the entropy effect of confinement also existed in our
forward, backward, or perpendicular to the channels experiment, and this made the interpretation more complex.
randomly, but the front-end speed of collective cells only
considers the cells that migrated forward (Figure 4D).
Moreover, the difference value of the magnitude of the 4.3. Underlying mechanism of millimeter-scale
front-end speed of collective cells and single-cell migration curvature on the cells
speed in various curvatures was varied. One of the reasons Previous studies demonstrated that cell behavior was
was that the front-end speed of collective cells included cell changed by the topographic cues due to the changes
proliferation, which was also influenced by curvature and in cell stress, which can activate the signal molecules
[44]
could compensate for the effects of random cell migration. and pathways of cells . For instance, the compressive
Another possible reason was that curvature could affect force can increase the expression of miR-494-3p in the
[45]
the proportion of cells moving forward, backward, and MC3T3-E1 cells to inhibit cell proliferation . Contrarily,
perpendicular to the channels during migration, which tension stress facilitates the cell proliferation of the
[46]
can be verified in the study’s next step. epidermal cell . Moreover, the cells align along with the
direction of maximum shearing stress , and the migration
[4]
4.2. Effect of channel width on cell’s is intrinsically motivated by force . Therefore, many
[29]
response to curvature force- and energy-based simulation methods, such as
The influence of channels with different widths (200, 150, self-propelled particles, cellular Potts models, and vertex-
100, and 50 μm), different radii (1.5, 2, 2.5, 3, and infinite based approaches, have been developed . Our model
[27]
mm), and the same cell diameter (20 μm) was compared was a vertex-based approach, which was modified based
in the simulation, which demonstrated that the migration on Odde’s model. The simulation results showed that the
speed increased as the channel width decreased regardless curvature influenced the cell migration by affecting the
of the curvature (Videoclips S4–8). Besides, the maximum cell–boundary interaction force and the number of valid
migration speed was observed at R1.5, R2, R2, and R2 pseudopodia. However, this approach simplified the cell–cell
when the channel width was 200, 150, 100, and 50 μm, and cell–boundary interactions to elastic collision, but

Volume 9 Issue 3 (2023) 47 https://doi.org/10.18063/ijb.681