Page 156 - IJB-9-1

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

tissues show partially similar mechanical properties, it from fully returning to its original shape after being
resulting in dramatic changes. Similar differences have subjected to excessive stress; the internal stress of the
been observed in various in vivo and in vitro experiments material progressively reduces over time (known as stress
that were cell-contained and decellularized. Although relaxation). Viscoelasticity is determined by the movement
these vastly different values cannot be converted, they are of polymer chains. As a result, it is influenced by a
not contradictory findings, but rather a reflection of the variety of variables, including temperature, stress, strain,
diversity in mechanical properties of the same tissue under frequencies, test time, and orientation. The characterization
controlled conditions. of viscoelasticity must be dynamic, applying programmed
The stiffness of the cell microenvironment is a dynamic strain over some time and measuring the response stress as
factor that varies with cellular activity over time. The a function of time, or applying stress and measuring strain
deposition of ECM, which is a dynamic network, occurs as a function of time. Programmatic temperature changes
during physiological processes as a result of cellular and frequency can also be used as variables, but they must
activity and influences cellular behavior. The conversion of be time-dependent.
cartilage to bone is a complex equilibrium by regulating the The dual properties of viscoelastic materials must be
turnover and remodeling of ECM . This process involves characterized by a complex modulus, which is typically the
[37]
multiple ECM-related components and is continuously storage modulus and loss modulus. The storage modulus
dependent on the stiffness of ECM . Abnormal ECM represents the elastic property of materials, which is the
[37]
stiffness leads to the occurrence and progression of the ability to instantaneously recover from deformation. It can
disease. For instance, a rigid ECM may engender the be divided into axial storage modulus (E′) and shear storage
transformation of normal epithelial cells into cancer modulus (G′) according to the direction. On the other
cells, increase tumor aggressiveness, and prevent drug hand, the loss modulus represents the viscous property
penetration into the tumor interior . Cells also exhibit of materials, which is the ability to irreversibly remodel
[38]
dynamic stiffness during various stages of their life cycle, over time. It can also be divided into axial loss modulus
and the variations in ECM stiffness that accumulate over (E″) and shear loss modulus (G″). In viscoelastic testing,
time can be monitored and may alter gene expression. the storage modulus and loss modulus are two functions
Primary human epithelial cells were passaged with of time. When the storage modulus is significantly more
increased stiffness on plastic petri plates, with cell stiffness than the loss modulus, the material is regarded to be solid;
rising two to four times after eight passages compared to when the loss modulus is much greater than the storage
cells passaged less than three times . With increasing modulus, the material is thought to be liquid; and when
[39]
passage number, the endometrial adenocarcinoma cells the storage and loss moduli are comparable, the material
grown on plastic petri plates showed a transition to the is said to be gel.
stromal phenotype, along with an increase in α-actin Stress relaxation is a common viscoelastic behavior
expression . Dynamic stiffness increases the variables in in living tissues, which can occur in ECM. It plays an
[40]
studies, which undoubtedly heightens the complexity of important role in tissues subjected to periodic loads, such
tissue engineering in vitro.
as cartilage, tendons, skin, and alveoli . More recent
[42]
2.2. Viscoelasticity studies have demonstrated that the stress relaxation of
[43]
Besides stiffness, biological tissues have other notable ECM affects not only cell differentiation , but also cell
[44]
[45]
mechanical properties. The water content of immature spreading and migration . The storage part of the
brain tissue is more than 80%, while that of normal liver cell deformation stress in the substrate is countered by
is about 65% . When water takes up a significant amount the stress relaxation of living tissue, which prevents cells
[41]
of space in tissues, its flow properties must be considered. from being continuously restrained when stretched, thus
This is known as viscoelasticity. The material in this resulting in a continuously changing dynamic effect on
situation has both, solid and fluid features. Viscoelasticity is the cells. However, the overall effects of stress relaxation
characterized by the combination of viscosity and elasticity on cells remain unclear; hence, the optimal viscoelastic
or the flow properties of viscous fluids and elastic solids. parameters for different tissue engineering have yet to be
investigated.
Viscoelasticity is a property of most living tissues and
polymer hydrogels that manifest as partly elastic and 2.3. Surface topography
viscoplastic. It is a dynamic mechanical microenvironment Surface topography is a concept that extends from 2D to
in the temporal sense. While a material is subjected to 3D. This concept was originally described on 2D cultured
moderate stress, it tends to return to its original shape, surfaces. The surface features of scaffold expansion are also
owing to elasticity. However, viscoplasticity prevents of relevance as cell culture progresses to 3D scales. Surface

Volume 9 Issue 1 (2023) 148 https://doi.org/10.18063/ijb.v9i1.632