Page 153 - IJB-9-1

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

extracellular calcium ions and the activation of electrical each bioprinting technique must be paired with specific
signals from the nervous system . Its physiological state is biomaterials, which are known as bio-inks. Some of the
[5]
also maintained by mechanical stress . The neuromuscular common combinations are as follows: low-viscosity liquid
[6]
junction, which allows cell-to-cell interaction, triggers materials for droplet-based bioprinting, donor substrate
action potentials in muscle cells; the concentration of for laser direct-writing , shear-thinning materials for
[13]
extracellular calcium ions, which determines the excitability extrusion-based bioprinting , and liquid photocurable
[14]
of muscle cells, is the chemical microenvironment, materials for stereolithography and two-photon
whereas the tension of tendon stretching muscle cells is bioprinting . Regardless of the technique, the primary role
[15]
the mechanical microenvironment. The activity of cells of bio-inks for living cells is the same; that is, as a substitute
is highly dependent on the microenvironment; hence, for ECM, thus providing a controllable microenvironment
cells are prompted to make adaptive changes in face of for cells. An ideal bio-ink should provide cells with a living
fluctuations in the microenvironment. This may lead to a environment comparable to that of the ECM.
series of physiological changes or even pathological system Currently, there is no bio-ink that can fully mimic the
imbalances . ECM, especially in the mechanical microenvironment.
[7]
The mechanical microenvironment has not yet been fully Given the diversity and potent modification potential of
explored, unlike the chemical microenvironment, which bio-inks, this goal remains achievable in the future. Bio-inks
has been extensively investigated. In the past two decades, have been recognized as vital vehicles for the modulation
a growing line of evidence has shown that mechanical of cell mechanical microenvironment in 3D bioprinting.
microenvironment plays a crucial role in regulating cell To date, some well-written review papers on bio-inks have
behaviors . Matrix stiffness, viscoelasticity, topography, been published with a focus on biofabrication techniques
[8]
and dynamic mechanical stimulation are all included in the or biological applications [12,16] . However, to the best of
cell mechanical microenvironment; synergistically, they our knowledge, there is no comprehensive summary of
determine the cell fate . For instance, multipotent stromal the engineered bio-inks used for 3D bioprinting of cell
[4]
cells can differentiate into bone, cartilage, or skeletal muscle mechanical microenvironment. Herein, we summarize the
tissue, depending on different matrix stiffnesses . Cells typical mechanical microenvironment of cells, which was
[9]
probe the mechanical microenvironment in various ways, used as a standard to compare the mechanical properties
and even if they are not adherent, cells in suspension rely of existing engineered bio-inks, as well as characterize and
on mechanical signals. Platelets control the coagulation propose some methods for ink selection. Following that,
process by sensing the stiffness of fibrin networks and the we discuss the limitations of previous studies and suggest
hydrodynamics of blood . This subverts the previous several future research directions.
[10]
understanding of mechanical signals and widens the
impact of the mechanical microenvironment on cells. 2. Cell mechanical microenvironments
Simple mechanical cues have been added into the In order to simulate the cell microenvironment in vitro,
culture requisites in tissue engineering for a better harvest. it is necessary to use the in vivo state as the standard
An example is the relocation of tissue engineering labs and reference. It is also essential to understand the
from rigid two-dimensional (2D) petri dishes to soft three- mechanisms by which cells sense their microenvironment.
dimensional (3D) biomaterials, as the spatially constrained As parenchyma, cells can passively withstand various
microenvironment and mechanical properties of 3D external mechanical stimuli and transmit mechanical
biomaterials are closer to those of in vivo tissues . In vitro, signals to the nucleus through the cell membrane and/
[11]
the effects of mechanical signals may be easier to observe or cytoskeleton to regulate cell behaviors (a process
[17]
but may also be neglected due to simplified conditions. termed as mechanotransduction) . Besides, cells can
Therefore, it is still a challenge to simulate and regulate cell also sense the mechanical microenvironment through the
mechanical microenvironment in a precise manner. cytoskeleton or by forming mechanical interaction with
the microenvironment. The cytoskeleton is an intracellular
3D bioprinting is a promising manufacturing method reticular organelle that is widely distributed in the cell,
for precise control of the cell microenvironment . and it consists of one of its three distinct subunits; i.e.,
[12]
Droplet-based bioprinting, laser direct-writing, extrusion- F-actin, microtubules, and intermediate filaments .
[18]
based bioprinting, stereolithography, and two-photon The regulation of the cytoskeletal network affects the
polymerization are the common types of 3D bioprinting. mechanical properties of cells, which in turn influence
The 3D bioprinting technology is well developed for the cell division, differentiation , and motility . The
[19]
[20]
fabrication of fine structures, thus enabling researchers to cytoskeleton itself has a certain mechanical strength and
construct fine and complex structures. Besides the structure, maintains the cell shape when the cell is deformed . It
[21]
Volume 9 Issue 1 (2023) 145 https://doi.org/10.18063/ijb.v9i1.632