Page 157 - IJB-9-1

International Journal of Bioprinting Bio-inks for 3D printing cell microenvironment

topography is often studied in instances where cells need to complicated. Mechanical stimulation to the material
be attached and proliferate, such as in the implantation of often causes displacements that may lead to simultaneous
metal joints in the body or polymer scaffolds. changes in various dimensions. The sliding of molecular

Roughness is one of the properties that characterize chains caused by material stretching changes the relative
surface topography. It describes the measurable change positions of cell attachment sites. The shift in the
in height of the material surface in a certain direction of attachment sites deforms the cell membrane and skeleton,
the profile. Roughness can be detected at different scales potentially generating mechanical signals. However, many
using a stylus profilometer (0.1 μm) , an AFM (0.01 nm) living tissue matrices have stiffness that varies with stress,
[46]
probe , or an optical apparatus (non-contact, resolution such as collagen and fibrin, whose substantial increase
[47]
depends on wavelength) . This property can be observed in stiffness following stress exceeds a critical value (i.e.,
[48]
with a scanning electron microscope . When the stress stiffening). These changes in stiffness can also
[49]
[58]
roughness is isotropic, unstructured, or nearly randomly be detected by cells . It is difficult to distinguish the
distributed, the increased roughness at the macroscale will factors that influence cell activities while attempting to
affect the wettability of the material, making the material refine the studies in view of the multiple mapping results
more easily wetted by body fluids and adsorb proteins, that correspond to one stimulus. Alike stress relaxation,
thus promoting cell adhesion . However, for cells, dynamic mechanical stimulation is a multidimensional
[50]
microscopic adhesion does not depend on the surface time-dependent environment.
height; instead, the molecular composition of the material 3. Properties of bio-inks
is more important than the smoothness of the surface. For
example, it is difficult for cells to attach to polyethylene Biomaterials used in 3D bioprinting can be classified as
glycol (PEG) hydrogels without the modification of hydrogel bio-inks and non-hydrogel scaffold materials.
arginylglycylaspartic acid (RGD peptide), no matter how Scaffold materials are pre-prepared and molded materials
rough the surface is . for cells to attach to, whereas bio-inks are encapsulated
[51]
If the roughness is anisotropic, structured, or regular, it and printed with living cells. Both, scaffolds and bio-inks
can be considered as a pattern. Reasonably designed patterns have basic biocompatibility, which allows cells to thrive.
The mechanical properties of materials are determined
can regulate cell behaviors; for instance, groove patterns can by the polymer backbone as the main component and the
regulate the alignment of cells , which plays an important intermolecular bonds, which can be covalent, ionic, and/
[52]
role in engineering microenvironments with anisotropic or hydrogen bonds, in addition to spatial topology. We
characteristics (e.g., cardiac cells and neurons) . Cells summarized the mechanical properties (range of modulus
[53]
prefer to grow along the long axis of the groove rather than values) of several commonly used bio-inks under different
spanning , which may be related to the slope distribution conditions (Table 2). In fact, the mechanical properties of
[54]
of the topography and the deformation of the cytoskeleton.
materials are affected by various factors. There are now
2.4. Dynamic mechanical stimulation more mechanical properties to choose from for materials,
At the macroscale, the majority of dynamic mechanical and their combinations and derivatives are constantly
stimulations based on the mechanical microenvironment being developed, making it easier to mimic native cell
are used to mimic the motion of genuine living tissues, mechanical microenvironment. Since 3D bioprinting has
such as the stretching of skeletal muscle, the shearing been extensively discussed as a standardized and common
of cartilage, and the tension of skin for scar tissue means of biofabrication in many works, we will not go into
formation. For instance, a stretch pattern of 25% stretch detail about 3D bioprinting. In order to ensure a focused
at 12-s intervals for 12 to 36 h resulted in a considerable discussion, this review may pay attention to materials for
activation of skeletal muscle satellite cells . This is extrusion-based bioprinting and stereolithography based
[55]
essential for muscle repair and regeneration. Induced on commonality and functionality.
mechanical shearing of synovial fluid with cartilage during 3.1. Hydrogel bio-inks
joint movement promptly activates latent transforming Almost all bio-inks contain hydrophilic macromolecules
growth factor-beta, which affects the biosynthesis of as the main chain in order to mimic the properties of
chondrocytes . For the skin environment, restrictions on ECM as closely as possible and improve biocompatibility.
[56]
skin stretching can slow the formation of keloids, as the As a result, bio-inks are in a hydrogel state following
incidence of keloids increases with skin tension, especially cell loading. Bio-inks are available in a wide range of
in cyclically stretched body parts . materials, but most of them are used for extrusion-based
[57]
When we focus on dynamic mechanical stimulation 3D bioprinting due to shear-thinning rheology. Those
at the microscale, the microenvironment may become that can be modified with photocurable groups and have

Volume 9 Issue 1 (2023) 149 https://doi.org/10.18063/ijb.v9i1.632