Page 136 - IJB-10-3

International Journal of Bioprinting New challenges in liver tissue engineering

Table 2. (Continued...)
Alg and Gel hiPSC-HLCs Pneumatic Square + – Increased cell density. 139
extrusion inner grid – Integrated cell morphology, proliferation, and functionality.
– Upregulation of CYP1A2 in bioprinted HLC after APAP treatment.
Gel, Alg and HepaRG Pneumatic Rectangular – Maintenance of viability up to 3 weeks. 132
Matrigel extrusion shape + – Increased levels of albumin production.
inner grid – Increased resistance to aflatoxin B1-induced hepatotoxicity (chronic
treatment lasting 7 days).
– Sensitive to doxorubicin-induced toxicity.
GelMA HepG2/C3A Hollow Dot array – Increased levels of albumin, A1AT, transferrin, and ceruloplasmin on 133
capillary day 30.
and piston – Sustained expression of cytokeratin 18, ZO1, and MRP2 cellular
system proteins.
– APAP treatment produced a decrease in cell metabolism and reduced
levels of albumin, A1AT, transferrin, and ceruloplasmin.
Liver dECM, HLCs, Pneumatic Hepatic – Increased viability 15 days after printing. 134
Silk and Gel HUVECs, and extrusion lobule shape – Upregulation of hepatic markers for HLC (albumin, phase I enzymes),
HSCs HUVEC genes (CD31 and vWF), and HSC (desmin) genes.
– HLCs were organized in aggregates with HSCs and HUVECs in a
sinusoidal-like layer around them.
– HSCs along HUVECs created a vascular network.
– Hepatotoxicity was assessed by testing six different drugs, making this
co-culture more sensitive and better at predicting hepatotoxic events
than HLC monoculture.
Liver fibrosis
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.
GelMA and HepG2 cells Digital Hexagonal – Reduced viability and proliferation in GelMA constructs. 136
porcine dECM micromirror shape – Higher expression of hepatic markers (ALB and AFP) on the dECM-
device based constructs than others.
(DMD) – Study of fibrosis by exposure to different matrix stiffnesses, simulating
fibrotic scenarios (soft, medium and stiff). Stiff hydrogels were
associated with a significantly reduced expression of MKi67, ALB,
and AFP. CASP8 apoptotic markers were also upregulated for the stiff
matrix.
– Genes related to angiogenesis (IGF2) and matrix metalloproteinases
(MMP2 and MMP9) were upregulated in stiff matrix, indicating
improved tumor progression (HCC).
GelMA Huh7, HepaRG, Pneumatic Cube and – Long-term viability (up to 28 days). 137
LX-2, and extrusion Square grid – Inducibility of metabolism enzymes
HUVECs – HepaRG showed markers related to polarization with E-cad and
N-cad on the apico/lateral membranes, as well as functional
transporter MRP2.
– Co-cultures of HepaRG and LX-2 cells allow detecting collagen
deposition and studying liver fibrosis.
Novogel 2.0 PHHs, HSCs, Pneumatic – Bioprinted constructs exhibit multicellular architecture of liver tissue. 140
HUVECs, extrusion – HSCs exhibit quiescent states.
– Chronic induction of fibrosis by methotrexate or thioacetamide for
up to 14 days resulted in increased collagen deposition and pro-
inflammatory cytokines.

(Continued...)

Volume 10 Issue 3 (2024) 128 doi: 10.36922/ijb.2706