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International Journal of Bioprinting New challenges in liver tissue engineering

Table 1. (Continued...)
PEG-tetra- UV-light/dithiol HepG2 and Huh7 – Orthogonally crosslinked thiol-ene hydrogel PEG system 106
norbornene crosslinker was cytocompatible for culturing Huh7 and HepG2 cells.
– The hydrogels that contained bio-active MMP-sensitive
peptide linkers could better upregulate the expression of
several hepatocyte-specific genes and enhance hepatocyte
functions.
– Inclusion of RGD motifs was also conducive for
augmenting hepatic functionality.
PVA Not described HepG2 – Collagen-coated scaffolds allowed the attachment and 118
viability of HepG2, while very few cells were observed in
non-coated scaffolds.
– Cell proliferation was significantly higher in the collagen-
coated scaffolds than in pure PVA scaffolds.
– Albumin secretion and urea synthesis were significantly
higher in the collagen-coated scaffolds than in PVA.
PNIPAAm Radical HL-7702 and HepG2 – The hydrogel was copolymerized with glycyrrhetic acid to 119
copolymerization with better interact with hepatocytes.
AIBN and TEMED – Hydrogel promoted cell adhesion and proliferation.
– Urea synthesis and albumin secretion were higher in
copolymerized hydrogels.
Polyisocyanopeptides- Temperature LGR5 liver stem cells – Organoids were formed when the hydrogels were modified 120
+
based hydrogel by laminin–entactin complex.
– Organoids proliferated within the hydrogels at rates very
similar to that in Matrigel.
– Hydrogels promoted stem cell differentiation confirmed by
the upregulation of several hepatocyte markers.
Abbreviations: AIBN, azobisisobutyronitrile; Col, collagen; dECM, decellularized extracellular matrix; GelMA, gelatin methacryloyl; GL, glycyrrhizin;
HA, Hyaluronic acid; HLC, hepatocyte-like cells; ICO, intrahepatic cholangiocyte organoids; iPSC: induced pluripotent stem cells; LEC, liver endothelial
cell; PEG, polyethylene glycol; UV: ultraviolet.

tissue engineering because it is cheaper and possesses a shear storage modulus that ranged from 100 Pa to 1
some of the advantages of Col. It is soluble in physiological kPa. HepG2 cells and HLC derived from human iPSC
buffers (not needing acetic acid) and forms a physical were successfully cultured within the hydrogels, after
hydrogel by reducing the temperature. The problem is grafting arginine-glycine-aspartic acid (RGD) adhesion
that the sol–gel transition happens below 37°C, forming motifs to HA, which secreted more albumin than
liquid solutions in cell culture conditions. This has led non-functionalized HA hydrogels. Heparin is another
to a search for alternative ways to crosslink Gel for use abundant glycosaminoglycan in liver ECM, with the
in tissue engineering. One of the most frequently used advantage that it binds ECM proteins such as the hepatic
methods is UV light crosslinking of gelatin methacryloyl growth factor (HGF) thanks to the presence of the sulfated
(GelMA), which has been tested in building 3D lobule-like group in its structure. For instance, heparin hydrogels
microtissues for culturing hepatocytes and fibroblasts. can be obtained by Michael-type addition reaction of
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The study showed that urea synthesis and albumin thiolated heparin and diacrylated PEG crosslinker. By
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secretion by HepG2 were significantly higher in co-culture the inclusion of HGF in heparin, single hepatocytes and
than in monoculture. hepatocyte spheroids showed excellent hepatic functions
In the group of glycosaminoglycans present in liver up to 20 days in culture.
ECM, hyaluronic acid (HA) has been proposed as a In addition to applying pure hydrogels for in vitro
suitable hydrogel for its high hydration capacity and systems in liver tissue engineering, combining different
mechanical stiffness, as well as the ability to interact with components of the ECM to produce hydrogels with
cells through the binding domains for the cell-surface improved characteristics, as described in a previous
receptors CD44 and RHAMM. An example of its use in study that established a biomimetic difunctional HA-Col
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liver tissue engineering has been described, in which hydrogel matrix to mimic different properties of natural
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HA was crosslinked using an 8-arm polyethylene glycol ECM, such as fast relaxation, a nanofibrillar structure, and
(PEG) by click chemistry, giving rise to hydrogels with rich adhesion domains, is gaining traction. The same
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Volume 10 Issue 3 (2024) 124 doi: 10.36922/ijb.2706