Page 139 - IJB-10-5

International Journal of Bioprinting Liver printing: from structure to application

as a hemostatic agent and sealant due to its remarkable native ECM, along with other biochemical cues present in
biocompatibility, support for cell adhesion, and minimal the original natural ECM. Currently, dECM from various
inflammatory and foreign body responses. Moreover, organs, including the liver, cartilage, heart, fat, skin,
fibroin monomers can polymerize into a gel via thrombin vascular tissues, and bladder, has been used in bioprinting.
solution catalysis. dECM can promote cell survival, differentiation, and long-
term functionality. Due to the poor mechanical properties
4.1.4. Alginate of dECM, it often requires blending with polymers for
Alginate is a linear anionic polysaccharide containing better structural stability. Deng et al. utilized liver dECM
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1,4-linked β-D-mannuronic acid and α-L-guluronic mixed with gelatin and sodium alginate as a bioink for
acid residues. Alginate is considered biocompatible and constructing an in vitro-expanded primary hepatocyte
biodegradable. At pH values below 3, it self-assembles (eHep cell)-loaded bioartificial liver. The addition of gelatin
into acidic gels through the formation of intermolecular and sodium alginate improved the mechanical properties
hydrogen bonds. Additionally, alginate can form physical of the liver dECM, providing the necessary mechanical
gels through synergistic binding with divalent cations such support for printing liver structures. The 3D-bioprinted
as Ca . liver cultured in vitro exhibited mature hepatic functional
2+ 120
4.1.5. Hyaluronic acid phenotypes, such as glycogen storage and drug metabolism.
Hyaluronic acid (HA) is a hydrophilic linear anionic Moreover, upon transplantation, it was able to extend the
polysaccharide composed of 1,3-β-D-glucuronic acid and lifespan of mice with liver failure. 129
1,4-β-N-acetyl-D-glucosamine residues. It is commonly 4.1.9. Polyethylene glycol
used as a lubricant to prevent postoperative adhesions. HA Polyethylene glycol (PEG) is a linear polymer composed
is commonly found in natural tissues and is an important of repeating ethylene glycol units (HO-CH -CH -OH)
component of the liver sinusoidal space. It possesses in its chemical structure. PEG is highly soluble in water,
2
2
excellent biocompatibility and can form hydrogels when compatible with other organic solvents, and exhibits
modified through esterification and crosslinking of its excellent biocompatibility. Simple PEG-based scaffolds
carboxyl or hydroxyl groups. Methacrylate-modified HA alone cannot promote cell adhesion, and cell apoptosis
can undergo photocrosslinking ; glycidyl methacrylate- often occurs due to the absence of cell-matrix binding
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hyaluronic acid (GMHA) promotes endothelial cell sites. PEG-based materials can be modified with RGD
proliferation, supports vascular formation, and has been
used to construct vascularized liver tissue. 122,123 derivatives to enhance cell adhesion or peptide sensitivity
to cell proteases (e.g., from the MMP family), for reshaping
130
4.1.6. Agarose and cell traction studies. PEG hydrogels crosslinked
Agarose has a gelation principle similar to that of by FXIIIa can be adjusted to a stiffness of ≈1.3 kPa, and
gelatin, forming a gel upon heating and cooling. It is incorporating key ECM proteins from the natural liver,
124
commonly used in 3D bioprinting as sacrificial material such as laminin-111, collagen IV, and fibronectin, into the
125
or mixed with other materials to adjust ink viscosity. PEG network facilitates the culture of liver organoids. 85
Specifically, agarose can be used to support the culture of 4.1.10. Pluronics
hepatocyte spheroids. 126
Pluronics are ABA triblock copolymers of various types,
4.1.7. Matrigel typically named with a letter followed by two or three
Matrigel is derived from mouse tumor ECM and digits. They are composed of polyethylene oxide (PEO)
basement membrane, containing 30% collagen IV, 60% and polypropylene oxide (PPO). Pluronic F127, widely
adhesive proteins (i.e., laminin), and 10% small molecules used in 3D bioprinting, generally undergoes temperature-
(elastin, heparan sulfate proteoglycan, fibronectin, etc.). induced gelation, remaining solid at higher temperatures
Matrigel contains growth factors, abundant proteins and and transitioning to a liquid state upon cooling. Due
peptides, and cell adhesion motifs, thus exhibiting good to its lack of bioactivity, Pluronic F127 is often used as a
biocompatibility. It can be used for angiogenesis, organoid sacrificial material to introduce vascular-like structures
culture, 3D cell culture, in vivo studies, drug screening, in hydrogels. 131
toxicology testing, disease modeling, etc. However, due
to the undefined composition of Matrigel, batch-to-batch 4.2. Cell types
variations limit its application and clinical potential. 127 Cells are also a crucial component of bioinks. The cell
sources commonly used for 3D bioprinting include stem
4.1.8. Decellularized extracellular matrix cells (ESCs, iPSCs) and somatic cells. In liver bioprinting,
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Decellularized extracellular matrix (dECM) contains primary hepatocytes are the most ideal natural cell source,
proteins and polymers in appropriate proportions to the possessing high metabolic activity and relatively similar in

Volume 10 Issue 5 (2024) 131 doi: 10.36922/ijb.3819