Page 160 - IJB-9-1

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

the influence of structures on the mechanical strength of 4.2. Surface topography
compact and cancellous bone. Surface topography or patterning is also a basic
microenvironment that necessitates both stiffness
Materials for high-temperature bioprinting cannot be and fabrication precision control. In this regard,
loaded with cells, and hydrogel bio-inks are required if a stereolithography has an advantage over extrusion-based
3D-wrapped matrix environment is needed. Synthetic bioprinting due to its higher resolution. There will be
polymer hydrogels such as PEG and PAAm, natural higher resolution for profile height with smaller layer
polymer hydrogels such as chitosan, gelatin, and alginate, heights. The most important initial factor affecting the
as well as chemically modified semi-natural hydrogels such structural resolution is the swelling of bio-inks, which is
as GelMA and hyaluronic acid methacryloyl (HAMA) can an equilibrium process of two opposite trends. Volume
be used as the main components to simulate the initial expansion occurs as a result of the penetration of solvent
stiffness. According to the specific needs in bioprinting, the into the hydrogel network, leading to the extension of the
polymer main skeleton can be chemically modified. With 3D molecular network and the polymer chain between
the exception of ECM-derived hydrogels (e.g., collagen, the cross-links, which reduces its conformational entropy;
gelatin, fibrin, and GelMA), most polymer hydrogels the elastic contraction force of the molecular network then
lack cell adhesion sites (bioinert). Hence, if they are not attempts to shrink the network. Except for solid scaffolds,
chemically modified (such as RGD peptides) or mixed all hydrogels swell at varying degrees after immersion,
with ECM analogs, cells are unable to transmit mechanical making the grooves and ridges disappear, and reducing
signals to the cytoskeleton through adhesion sites even if the resolution of patterns and blurring boundaries. The
the stiffness is similar, thus behaving in an abnormal state. network dilution caused by the swelling behavior leads

The initial stiffness of hydrogels is controlled by the to a dramatic decrease in the mechanical strength of the
[71]
concentration and degree of cross-linking. Generally, hydrogel . Hence, bio-inks with a low swelling ratio are
[72]
increasing the concentration of substances in hydrogels can preferred , and swelling strengthening hydrogels using
[73]
increase the stiffness, thus providing an easier substrate for embedded networks is also an effective solution to this .
cells to attach to. Increasing the cross-linking density of gel
can also increase the stiffness while maintaining the same 5. Complex mechanical microenvironment
substance concentration. For example, GelMA with a 96% and challenge for bio-inks
degree of substitution has a Young’s modulus of 3.08 kPa
at a concentration of 5%, which increases to 184.52 kPa Real living tissue is far more complex than a hydrogel
at a concentration of 30% . The same 10% concentration with fixed stiffness. When controlling one of these cues,
[68]
of GelMA hydrogel has a compressive Young’s modulus the conditions in other dimensions tend to vary from the
of 9.23 kPa with 81.3% degree of substitution, but only optimum, especially for living tissue, such as the flaws in
5.66 kPa for the hydrogel with 41.6% degree of substitution. plasticity in high stiffness materials, a lack of stress relaxation
This indicates that increasing the degree of substitution that may confine cells, and so on. In the current field of
can increase the cross-linking density . research, this is an unsolved challenge. As a result, most
[69]
studies focus on mechanical microenvironments with a
There are limitations to the microenvironment stiffness narrow range of factors, while other distortions are omitted.
raised by the concentration and cross-linking density. Occasionally, these omissions are acceptable for research
Since the spreading and movement of cells depend on the progress. It is possible to have multiple design strategies for a
space between the molecular chains in the hydrogel, the particular mechanical microenvironment, and comparable
living space of the cells would be limited if the substance aims can be achieved with the use of diverse bioprinting
concentration is too high. This would in turn lead to materials, which is not constrained to a single solution.
problems in cell growth and proliferation. Developing the
double-network system, which comprises two hydrogels 5.1. Anisotropic mechanical microenvironment
with separate elastic networks, is one way to overcome A shared disadvantage of commonly used bio-inks is the
this constraint. After cross-linking, the two networks nest mismatch between their mechanical properties and isotropy
inside each other, enabling sliding when deformed and with in vivo tissues. Unlike natural tissues with uneven
conferring the total system a larger elastic modulus with distribution, bio-inks lack anisotropy and complexity. They
better mechanical properties than the two single-network are unable to exhibit the diverse mechanical properties of living
hydrogels. GelMA, for example, can be stiffened on tissues at different scales even with the fabrication of similar
modulus by adding low amounts of HAMA (1% w/v), and structures. Considering the differences in the mechanical
its mechanical properties are superior to monohydrogel microenvironment of living tissue at various scales, there
systems with high concentrations . will be many challenges encountered when designing and
[70]

Volume 9 Issue 1 (2023) 152 https://doi.org/10.18063/ijb.v9i1.632