Page 47 - IJB-9-3

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

1. Introduction form the induced patterns in the present study; siliconized
glass, which adheres well to both cells and PCL, was
Most native tissues contain curved architectures to selected as the substrate.
maintain their mechanical and physiological function,
and the curved topographic environment is expected to Several computational models have been proposed
influence the behavior and function of the surrounding to pursue the mechanism of how curvature affects
[27]
cells [1-3] . The curvature changes in the tissues have been cell behavior . Finite element methods used thermal
found to lead to severe diseases, such as asthma induced stress to replicate cell contraction and calculate the
[4]
by the airway narrowing , distorted vision due to the direction of the maximum principal stress, which
[5]
keratoconus bulging or flattening , and vertebral was found to be a governing factor in determining the
disorders caused by the spine bending . Furthermore, orientation and migration of collective cells on the
[6]
the curved structures of artificial tissue engineering curved channels [28,29] . Energy minimization methods can
scaffolds can affect the behavior of seeded cells, which forecast the morphology changes of cells [30,31] . In addition,
is crucial in clinical and biomedical applications [7-9] . cell migration can also be calculated by vertex-based
Recent studies focused on the effect of micro- and methods that mesh individual cells into numerous nodes
nano-scale spatial curvature on cells, showing that the and analyze each node’s migration direction and distance
cellular-scale curved structures can alter the adhesion [10] , according to the condition of force equilibrium [32,33] .
orientation [11,12] , migration [13,14] , and gene expression [15] Odde’s model was based on one of the vertex-based
of cells. However, the tissue curvatures perceived by methods, which was developed to investigate the
[34]
cells are also present on a millimeter scale [16] . Therefore, influence of substrate stiffness on cells . Shih et al.
it is essential to probe the influence of millimeter-scale modified Odde’s model by increasing the force of cell–cell
curved structures on cells. and cell–boundary interactions and making it suitable
for simulating cell migration in a confined 2D space .
[35]
A suitable method is required for the fabrication of However, none of them have been used to stimulate cell
millimeter-scale structures. Various methods have been behavior on curved channels.
employed to fabricate curved structures to guide cell
behavior, including photolithography and mold [17,18] . Here, we aim to explore the effects of planar milli-scale
However, the main disadvantages of photolithography and curved channels on the cells. PCL curved structures with
mold are high manufacturing costs and the inability to radii 1.5, 2, 2.5, 3, and infinite (straight) mm were printed
change the designed patterns. As one of the 3D printing onto the siliconized glass sheets by FDM to observe the
technologies, fused deposition modeling (FDM) extrudes proliferation, morphology, orientation, and migration
and deposits the melted thermoplastic materials with of cells within these channels. The glass sheet without a
designed patterns layer by layer and then solidifies them pattern was used as a control. Our results revealed that
by cooling . The most crucial feature of FDM is that it the cells behave distinctly under the guidance of different
[19]
can flexibly print the structures with desired shapes at a curvatures. Also, we investigated the underlying mechanism
[20]
low cost . The diameter of fibers printed by FDM was of cellular curvature sensing observed in the experiments.
greater than 200 μm in most previous studies. For instance, A computational model based on force equilibrium was
Zhang et al. fabricated the meniscus scaffold with 300 μm developed to simulate the migration of cells in the curved
[21]
diameter poly(ε-caprolactone) (PCL) fibers . Ji et al. channels and served as an experiment complement to
printed curved PCL fibers with 460–516 μm in diameter decipher the key factors in the process of cellular response
to enhance mesenchymal stem cell osteogenesis . Cells to curvature. Our simulation results demonstrated that the
[22]
can perceive the topographic structures with dimensions effect of curvature on cells originated from the change in
comparable to their own [23,24] . Two-stage temperature the cell–boundary interaction forces and the number of
control, which uses two heating blocks to reconcile the valid pseudopodia generated by the cells. Together, our
flowability and formability of the thermoplastic materials, findings provide a simple and effective way to manipulate
is an effective way to obtain precise and homogeneous cell behavior with curved channels, opening new avenues
fibers with a diameter of ~100 μm in FDM. Thus, FDM is for the design of artificial tissues with desired geometric
an effective way to fabricate curved structures. features.
PCL has been approved by the U.S. Food and Drug
Administration (FDA) as biomedical material due to 2. Materials and methods
its fantastic biocompatibility, biodegradability, and The experimental procedures for investigating the effect of
environmental friendliness [25,26] , and it is thermoplastic and curvature on cell proliferation, morphology, orientation,
suitable for FDM printing. Therefore, PCL was chosen to and migration are represented in Figure 1.

Volume 9 Issue 3 (2023) 39 https://doi.org/10.18063/ijb.681