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International Journal of Bioprinting New challenges in liver tissue engineering

Table 2. (Continued...)
Novogel 2.0 PHHs, HSCs, Pneumatic – Incorporating KCs does not affect functionality (urea and albumin 141
HUVECs, and extrusion production).
KCs – The addition of KCs reduces the response to pro-fibrogenic drugs
(TGF-b and methotrexate).
– KCs salter cytokine responses in tissues with mild injuries.
GelMA HepG2-C3A DLP Hexagonal – HepG2/C3A and its co-culture with LX-2 cells were 90% viable 14 142
and LX-2 cells Bioprinting shape days after printing.
– LX-2 cells tend to migrate to the peripheral parts of the hexagonal
construct, mimicking the native tissue organization.
– Co-culture showed a more efficient uptake of fatty acids. Complex
models confirmed better outcomes in replicating the behavior of the
native tissue.
– Adding TGF-β1 enhanced the fibrotic state of the cells. Albumin and
urea levels were reduced due to the growth factor.
Liver cancer
Gel and Alg HCC (from Pneumatic Cube – Better viability than 2D culture. 135
donor tissue) extrusion – HCC tumorigenic potential for individual patients, after in vivo
implantation on mice, was confirmed by AFP expression and Ki67 for
proliferation rates.
– Drug screening with four commonly used drugs in treatments showed
a dose-dependent pattern in almost every case.
Gel-Alg- Intrahepatic Extrusion Grid-like – High survival and proliferation. 143
Matrigel cholangiocarci- hydrogel – Expression levels of tumor markers, cancer stem cell markers, matrix
noma metalloproteinase protein, index of tumor fibrosis, index of liver
function, and epithelial–mesenchymal transition regulatory proteins.
– Bioprinted cells showed anti-cancer drug resistance.
Metabolic associated fatty liver disease
Scaffold-free Zucker rat 9×9 needle – Liver model maintained MASLD disease pathology for at least 3 144
hepatocytes array weeks
Abbreviations: AFP, alpha-fetoprotein; ALB, albumin; Alg, alginate; APAP, acetaminophen; Col, collagen; dECM, decellularized extracellular matrix; Gel,
gelatin; HCC, hepatocellular carcinoma; HLC, hepatocyte-like cells; HSC, hepatic stellate cells; HUVEC, human umbilical vein endothelial cells; KC,
Kupffer cells; MMP, matrix metalloproteinase; PHH, primary human hepatocytes; vWF, von Willebrand factor.

7. Liver tissue engineering approaches for source that can be differentiated into any of the body’s cell
treating liver disease types, including hepatocytes, these cells could overcome
Liver cell transplantation is an alternative to organ one of the major limitations of liver cell therapy, or they
transplants and an option for patients with different types could be also used as a personalized medicine approach
of liver disease, including inborn errors of metabolism and with patient-derived cells.
end-stage liver disease. 145,146 However, the low engraftment Different animal models have been proposed to test
and repopulation of transplanted hepatocytes 72,147 the therapeutic potential of the developed strategies. Most
have prompted the use of alternatives based on tissue of these involve ALF models induced by acetaminophen,
engineering principles. Liver cell therapy enabled through thioacetamide, or D-galactosamine for testing the
tissue engineering involves creating functional liver tissue therapeutic efficacy of the engineered liver systems. 117,150-152
for regenerating diseased organs. Different strategies are However, other disease models, such as the Wilson disease
used to produce liver tissue to restore the hepatic functions animal model, have also been used to show the clinical
of a diseased liver, such as decellularized–recellularized effects of the developed grafts.
153
tissue, scaffolds, or hydrogels. Regarding cell types, The different systems used and their major outcomes,
148
149
95
although different researchers have used hepatocytes of organized by liver diseases, are detailed in Table 3.
human or animal origin to treat different diseased animal
models, others have used multipotent stem cells (i.e., Decellularized liver tissue is an ideal scaffold since
different mesenchymal stem cells). iPSCs differentiated it retains the natural liver ECM vascular network,
into HLC have also been explored, generating interesting microarchitecture, and components. dECM could be
154
results. Since iPSCs offer an unlimited and available cell used directly as a scaffold or as hydrogels for the treatment

Volume 10 Issue 3 (2024) 129 doi: 10.36922/ijb.2706