Page 163 - IJB-9-1

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

water content. It can be observed in PAAm that as its differences exhibited by living tissues at different scales
water content decreases, the gel becomes more brittle . need to be further explained. Therefore, much research
[72]
The mechanical reinforcement of brittle hydrogels through is still needed to determine whether the results, after
multi-network cross-linking or designing enhanced disregarding these unknown quantities, can be used as a
microstructures to improve compressive strength can help real response to the mechanical microenvironment.
materials adapt to more dynamic mechanical tests. Considering the limitations of the development of

6. Conclusion and prospect materials science, bio-ink materials are still far from being
perfect in mimicking the properties of native ECM. They
Through the continuous research in recent years, a have poor stiffness tunability and different stress relaxations
growing number of influencing factors of cell mechanical from natural tissues, which are not conducive for ECM
microenvironment have been uncovered and the remodeling in cells. In view of these disadvantages, a large
principle has gradually become clearer. The use of bio- number of uncontrollable factors have been disregarded
inks and scaffold materials to engineer cell mechanical by many studies. However, in recent years, with the
microenvironment via 3D bioprinting has good feasibility emergence of four-dimensional bioprinting technology
and broad prospects for application, whether for and the development of smart materials, materials that
mechanism exploration, drug testing as a disease model, can actively change their mechanical properties, such as
or tissue regeneration simulation. Although it would be self-deforming printed structures , are also increasing,
[82]
impractical to list out all of the application scenarios, a and stiffness-adaptive dynamic-structure host–guest–
clear selection strategy can be obtained by summarizing macromer hydrogels, which are more favorable for cell
the methods and experiences. First, it is important to motility, have also been identified . These discoveries will
[83]
identify which mechanical cues (stiffness, viscoelasticity, inevitably expand the boundaries of in vitro stimulation of
surface topography, or mechanical stimulation) in the cell mechanical microenvironment and steadily advance
native cell microenvironment we attempt to mimic in in simulation research.
vitro engineered cases. Then, the mechanical cues in native
living tissues (as control) need to be examined, while Acknowledgments
determining the approximate range of its variables. Third,
materials with mechanical properties similar to the target None.
tissues should be selected. Finally, by optimizing the details Funding
(constants and variables), the simulated microenvironment
would be able to mimic the native tissue. This work was financed by the NSFC National Natural
However, from existing studies, the difficulty in Science Foundation of China (11972280).
horizontal comparison has always been an obstacle to Conflict of interest
repeated research and the accumulation of experiences.
Whether on the macro or micro scale, either in tensile The authors declare no conflicts of interest.
or shear directions, the variable that controls is critical
and should be ensured to precisely match the research Author contributions
objectives. Rather than bulk stiffness, surface stiffness Conceptualization: Yanshen Yang, Feng Xu
should be used as the standard of comparison when Investigation: Yanshen Yang, Yuanbo Jia
controlling variables for material surface adhesion. Young’s Writing – original draft: Yanshen Yang
modulus and shear modulus should not be compared Writing – review & editing: Feng Xu, Qingzhen Yang
horizontally, while AFM and rheometer results should not
be compared in the same system either. When referring Ethics approval and consent to participate
to stiffness experiments from other literature, the focus
should be on the comparability of experimental methods. Not applicable.
Mutually exclusive variables are also challenging for
mechanical microenvironment simulation. For example, Consent for publication
when matrix stiffness is controlled by concentration, Not applicable.
the space of molecular chains changes, which virtually
restricts the cell’s movement and remodeling behavior. Availability of data
Moreover, the effect of macrostructure on the mechanical
microenvironment is still unknown. The mechanical Not applicable.

Volume 9 Issue 1 (2023) 155 https://doi.org/10.18063/ijb.v9i1.632