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International Journal of Bioprinting Bioprinted tissue-on-a-chip in drug screening
not trigger an immune response from encapsulated cells, lines, and the restored bioink after the shear thinning state
leading to the reserved biocompatibility of dECM. In retained most of the structural features, demonstrating
contrast, non-animal-derived bioink causes an immune its self-healing ability. The pore structure within the
response as well as the change of pH and temperature in microarchitecture plays a crucial role in material diffusion
microenvironments. and cell migration. Wang et al. developed a bioink with
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Like other bioinks, the addition of dECM enables an emulsion system, which facilitated the generation of
bioprinted bioinks to regulate viscosities, reduce shear multiple interconnected micropores. These micropores in
stress, and help cells proliferate after printing and form bioink were beneficial for the proliferation and distribution
a self-supporting structure. However, the mechanical of cells in deep structures. When taking GelMA as the
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properties of dECM do not meet the requirements of dispersed phase and dextran as the continuous phase,
supporting 3D constructs. Moreover, dECM fails to be methacrylated galactoglucomannan, acting as the
perfectly copied in vitro because of the differences between emulsifier in this system, was added to enhance cell
individuals, organs, and even tissues. dECM is extracted viability promote intercellular communication (Figure
from ECM via methods of cell removal. Uncontrolled and 3A). Two-component bioink is subjected to oxidation
unstandardized methods lead to degradation of dECM at or modification to obtain specific chemical groups that
different degrees during extraction processes, contributing interact with groups in other components, resulting in
to differences between batches. The strong specificity of more stable covalent bonds. Biological substances, such
dECM could explain why popularizing dECM on a large as polypeptides, are introduced to enhance cell adhesion
scale remains challenging. and biomimetic properties. In general, bioinks mimicking
functions of ECM provide gas exchange, facilitate material
3.1.2. Examples of hydrogel bioinks transport and removal, and offer physical support for
The single-component natural bioink cannot experimental cultures. Moreover, advanced hydrogels
simultaneously meet the requirements for molding during can selectively enrich or deplete molecules. For example,
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the printing process and the suitability of viscosity on the Zhang et al. exploited a functional hydrogel system that
growth of cells encapsulated in bioinks, so two-component consumed reactive oxygen, thus protecting cells from
and even multi-component hydrogels are applied to break oxidative stimulation (Figure 3B).
the mutual limitation of molding and cell culture. Moreover, 3.1.3. Synthetic polymers
the mechanical properties of bioink may be improved Despite non-natural sources, research certified that
through crosslinking. The alginate component in the synthetic bioink has biological correlations in cell culture.
alginate/GelMA bioink enabled the initial consolidation of Synthetic polymers with high inertness and resistance
the bioink, and GelMA formed the covalent bonds after are artificially produced for specific purposes. Synthetic
photocrosslinking to conglutinate the interlayer bioink. polymers are blended with natural bioink to promote the
This process completed the entity construction of a cell- mechanical properties of the mixed bioink and offset the
friendly bioink at a low concentration. Soltan et al. disadvantages of natural bioink. Since the polymers are
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investigated the synthesis of alginate dialdehyde because non-animal and non-human derived, their toxicity may
the human body lacked alginate sodium enzymes, and restrict cell viability. Moreover, the targeted cells can not
the increased oxidation degree of alginate dialdehyde adhere to the synthetic polymers, contributing to cell loss
promoted biodegradation. The oxidized and methacrylate at the beginning of model constructions.
alginate (OMA) bioink also underwent ion crosslinking
and photocrosslinking. However, the methacrylate bonds Polyethylene glycol (PEG) is an ethylene oxide
for photocrosslinking were obtained by the esterification polymer with high cytocompatibility, commonly seen as a
of the groups in alginate rather than the involvement of constituent of capsules. It is used in wound dressing for
GelMA. On the premise of ensuring mechanical stability, hemostasis and pharmaceutic preparations to enhance the
this bioink showed a high resolution and rapid recovery stability of the drug-loaded nanoparticles. 80-82 The ability
capability, simultaneously supporting a high survival rate of PEG to support cell adhesion allows for its further
of cultured stem cells. Cui et al. developed a three- application in tissue engineering. Aliphatic polyester,
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component bioink using natural proteins/polyphenols/ polycaprolactone (PCL) consisting of acetate, has a
polysaccharides. The hydrogel construct was shaped melting point of 56–66°C. Notwithstanding that PCL is
through hydrogen bonding and electrostatic interactions degraded by most natural microorganisms, it is difficult
after the ion crosslinking of alginate. The addition of to be enzymatically degraded in vivo. Liu et al. printed
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polyphenols disrupted the protein structure in gelatin, the gelatin solution between PCL bands for cell support
exposing more reactive sites for crosslinking. The initial (Figure 3C-I). Notably, 92% cell viability was maintained
hydrogel had structural features in the form of sheets and after a 7-day culture (Figure 3C-II). Furthermore, the
Volume 10 Issue 3 (2024) 179 doi: 10.36922/ijb.1951

