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

Figure 1. Bio-inks for bioprinting cell mechanical microenvironment mimicking the native microenvironment. Engineered cell mechanical microenvi-
ronment with bio-inks can be classified into two types: static and dynamic. Common static mechanical microenvironments include stiffness and surface
topography; matrix stiffness affects a single cell’s spreading, while surface topography regulates alignment. Common dynamic mechanical microenviron-
ments include stress relaxation, mechanical stimulation, and gradients; stress relaxation is a state in which strain is maintained and stress decreases over
time; tensile or shear forces from different directions are applied in dynamic mechanical stimulation; stiffness gradients can alter cellular behavior over
time and space.

also provides a scaffold with increased surface area for the engineering can benefit from modulating mechanical
motor proteins , so that these proteins can be transported signaling. The mechanical cues in cell microenvironment
[22]
on it to govern cell movement or generate internal stress. include stiffness, viscoelasticity, surface topography, and
Through the cytoskeleton, cells are connected to the dynamic mechanical stimulation (Figure 1).
outside world (neighboring cells or ECM network), and
they can deform, depolymerize, and reorganize in response 2.1. Stiffness
to changes in the mechanical microenvironment, resulting Stiffness is a material mechanical concept that reflects the
in noticeable changes in gene expression. ability of an object to resist deformation under an applied
force. In the elastic range, stiffness is usually determined by
In recent years, there has been a discovery of several
mechanical signaling pathways, involving yes-associated the ratio of the applied force to the displacement produced
by the force along the same direction. For most solid
protein/transcriptional coactivator with PDZ-binding materials, stiffness is widely applicable to a given structure.
motif (YAP/TAZ) activity , Lamin , and myocardin- Since many objects are anisotropic (exhibiting different
[23]
[24]
related transcription factors family , which are affected properties in different degrees of freedom), stiffness is
[25]
by matrix stiffness, cell density, or dynamic stretch and a structure- and boundary-dependent property that
shear. Changes in the mechanical microenvironment characterizes the macroscopic mechanical properties of
may alter the cytoplasmic nuclear translocation of the materials. Another measurement unit of an object’s ability
effector molecules, thereby affecting cell proliferation to resist elastic deformation is the elastic modulus, which is
and differentiation . Several diseases have also been defined as the ratio of stress to the strain of an object in the
[26]
found related to the dysregulation of mechanical elastic deformation region. According to different stress
signaling pathways. For instance, mutations in protein and strain directions, the elastic modulus can be divided
dystrophin that provides mechanical balance to muscle into Young’s modulus (E, tensile stress and tensile strain)
cells may lead to muscular dystrophy . However, it is and shear modulus (G, shear stress and shear strain).
[27]
still unclear whether and how the mechanical signals
in the microenvironment synergistically regulate cell In a strict sense, the definition of stiffness is inseparable
behaviors. Engineering cell mechanical microenvironment from structural conditions and is used to characterize
in vitro that recapitulates the native microenvironment the macroscopic structure rather than the properties
will be beneficial to researchers in clarifying how tissue of the material itself. The elastic modulus reflects the

Volume 9 Issue 1 (2023) 146 https://doi.org/10.18063/ijb.v9i1.632