Page 186 - IJB-10-3

International Journal of Bioprinting Bioprinted tissue-on-a-chip in drug screening

bioink to diffuse are superior in the visual investigation of which maintains a stable hydrogel state at 37°C. Moreover,
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cell–cell and cell–matrix crosstalks. another significant advantage of GelMA is the simplicity
of stiffness regulation. In photocrosslinked printing, the
3.1.1. Natural polymers structure with high resolution is formed by GelMA at low
Natural polymers are extracted or separated from natural concentrations by means of simple optimizations. The
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substances, such as alginate, gelatin, hyaluronic acid, concentration of GelMA and photoinitiator are critical
collagen, and fibrin. determinants of structural integrity.
Alginate with non-Newtonian fluid properties Components of ECM such as collagen, hyaluronic
composed of β-D-mannuronic acid (M section) and α-L- acid, and fibrin are applied as bioink to enhance functional
glucuronic acid (G section) is a negatively charged linear relevance. Collagen that belongs to the insoluble fibrin
polysaccharide extracted from brown seaweed. The G preserves the stiffness and integrity of ECM, supporting
section in sodium alginates crosslinks with polyvalent the morphological structures of the skin. Collagen
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cations (Ca , Ba ) to form the gel network, and the high is compatible with other biotic components due to its
2+
2+
content of G section contributes to alginate stiffness. pervasiveness in vivo. More than 90% of the cell viability
After being printed out of the bioprinter, rapid gelation was maintained in collagen without photo-crosslinking at
is required for bioinks. Alginate is difficult to mold at high concentrations, indicating that this bioink has lower
room temperature. Alginate often crosslinks in non- toxicity and immunogenicity. Collagen as bioink has
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covalent manners by ion crosslinking and self-assembly, been used to construct liver and neurological models. 64,65
which are dependent on hydrogen bonds or electrostatic However, the mechanical properties of collagen, composed
interactions. The hydrogel network produced by these of triple helices, are too weak to allow individual printing
methods has a weak internal force, while the intensity of construct. Three solutions are available for addressing
is expediently regulated by concentration, pH, and this issue: (i) chemical modifications; (ii) changing the
temperature. The mechanical property of bioink refers printing carrier and using collagen as the support bath or
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to the ability to support scaffolds embedded with cells removing sacrificial ink after printing in collagen; and (iii)
as long as possible during culture time. Alginate gel at using collagen as an adhesive in the bioink. In addition,
lower concentrations tends to have less aperture and total since animal-derived collagen bioink is not conducive to
areas, and higher concentrations with good mechanical the fabrication of complex structures and triggers immune
properties have the lowest cell viability and almost no response from human-derived cells, Wang et al. replaced
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cell spreading. Additionally, alginate contains abundant the traditional collagen with recombinant human collagen,
carboxyl (-COOH) and hydroxyl (-OH) groups, which which was modified by methacrylic anhydride and
are covalently connected through various processes such later crosslinked by 1-ethyl-3-(3-dimethylaminopropyl)
as polymerization, condensation, click chemistry, and carbodiimide hydrochloride/N-hydroxysuccinimide (EDC/
radiation. These linkages lead to constructs with high NHS). This crosslinking bioink with biocompatibility, high
mechanical strength and integrity. When mixed with porosity, and long degradation time was proven to provide
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other bioinks, alginate is used as the constituent to improve potential microenvironments for cultured cells.
the mechanical properties of the bioink.
Decellularized extracellular matrix (dECM) can be
Mammal-derived gelatin, similar to the amino acid derived from animal tissues. Considering heterogeneity
composition of collagen in humans, is the hydrolysis and residual interfering substances from animal-derived
product of collagen from pig skin, cowhide, and bone. The ECM, human-derived ECM is gradually applied for drug
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bionic nature of gelatin provides appropriate conditions for screening models. There are three extraction methods
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cell differentiation. In the construct composed of oxidized for dECM: physical methods suitable for small tissues,
alginate and gelatin, Distler et al. achieved the proliferation chemical methods, and enzymic methods. Except for cells
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of mouse myoblast cells and the directed differentiation of and genes, acquired dECM with similar organizational
ordered myotube clusters. During the gelation process, integrity and components to the original ECM can
molecules in gelatin are interconnected by non-specific induce the corresponding stem cell differentiation and
bonds, such as hydrogen and electrostatic bonds, which are tissue regeneration. 68,69 Except for the cells, the structural
easily depolymerized under high temperatures. Gelatin components of original organs are retained in dECM. In
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with poor mechanical and unique thermo-reversible theory, in the condition that the degradation of dECM
properties dissolves at 37°C; thus, its side chains are often does not affect the mechanical properties of the bioprinted
modified. The most used modified gelatin is gelatin construct, as long as it does not collapse, the degradation
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methacrylate (GelMA), obtained through the reaction rate of dECM may equal to the rate at which cells produce
of methacrylic anhydride with amino groups in gelatin, the new ECM. The degradation products of dECM may
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Volume 10 Issue 3 (2024) 178 doi: 10.36922/ijb.1951