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International Journal of Bioprinting Three-dimensional bioprinting in toxicological research

These are the first steps in creating transplantable liver grafts 10. Challenges and perspectives
that can be implanted back into the patient.
Stem cells derived from the embryonic connective tissue
Another artificial liver tissue graft, the mini-liver, may also of mesoderm origin, that is, mesenchyme, do not have the
be suitable for tissue regeneration or replacement. During the ability to form gametes, but being multipotent cells, they
creation of the mini-liver, a 3D structure was created using are able to differentiate into many different cell types within
a hydrogel and then implanted into nude mice after partial the body. In humans, they are found in the bone marrow
liver resection and radiation-induced liver damage. Mice and non-marrow tissues such as placenta, umbilical cord,
were divided into four groups: control, hydrogel, hydrogel adipose tissue, muscle tissue, corneal stroma, and dental
with HL-7702, and hydrogel with HGF. It was found that the pulp of deciduous teeth. In addition to tissue formation,
hydrogel did not reduce viability and did not interfere with these stem cells are involved in tissue regeneration and
cellular functions, and after implantation of the hydrogel, play a significant regulatory role in inflammation and
which also contained hepatocytes, liver regeneration was carcinogenesis. Taking advantage of this ability, they are
enhanced and the individuals showed longer survival times. suitable to be used for therapeutic purposes and in the field
Personalized therapies are facilitated by the creation of of regenerative medicine.
various artificial liver tissues, such as the Organovo ExVive During biofabrication or tissue engineering, a complex
™
system, which is suitable for studying DILI and related biological structure is created, which is almost identical in
mechanisms at the tissue level. Several manufacturers morphology and function to the native organ. Using raw
provide artificial and bioprinted 3D liver tissues composed biomaterials, cells, matrices, and engineering precision, these
of liver tissue-specific cells, such as hepatocytes, hepatic organ modules are printed, which, due to their similarity
stellate cells, Kupffer cells, and endothelial cells (Table 3). and function, can be used for regeneration or replacement

Table 3. Bioprinted and artificial liver models for transplantation
Device Manufacturer Description
ExVive ™ Organovo ® 3D bioprinted human liver tissue or functioning artificial liver tissue, which is
suitable for in vitro investigation of DILI
™
Hepa-Mate /HepatAssist HepaLife Biological artificial liver, cryopreserved porcine hepatocytes
Scaffold-free liver structure Cyfuse Bioprinted scaffold-free liver spheroids, which can be used for in vitro testing
3D liver tissue Pandorum Technologies 3D hepatocytes spheroids, which are capable of long-term albumin secretion
and CYP expression and suitable for DMPK and hepatotoxicity studies
3D liver tissue Pandorum Technologies 3D liver organoids, which contain parenchymal hepatocytes, Kupffer cells, hepatic
stellate cells and liver endothelial cells and are suitable for NASH drug discovery
Mini liver Pandorum Technologies Prototype of implantable vascularized organoids for bioartificial liver with a
potential of engrafting by transplantation
HμRELhuman /HμRELhumanPool ™ HμREL Corporation Self-assembling primary hepatocyte-based microlivers co-cultured with
®
™
non-parenchymal stromal cells in microtiter plates
HepaPredict system HepaPredict 3D spheroid system based on freshly isolated primary hepatocytes co-cultured
with non-parenchymal cells
3D InSight Human Liver Microtissues InSphero Pharma-validated in vitro co-culture model of primary human hepatocyte, Kupffer
™
cell and liver endothelial cell, which originate from 5 female and 5 male donors
3D InSight Human Liver Steatosis InSphero Disease model of first stage of non-alcoholic fatty liver disease, which consists of
™
Model a microtissue produced from a co-culture of healthy human primary hepatocytes,
Kupffer cells and liver endothelial cells combined with special media and lipids
3D InSight Human Liver NASH Model InSphero Advanced tuneable microtissue co-culture of healthy primary human liver
™
cells, which is suitable for drug testing
HepatoPearl Cyprio 3D in vitro model of primary human hepatocytes with high predictability and
size-controlled spheroids, which is developed using the BioPearl technology
3D human cell culture platform Invitrocue ® 3D co-culture model of primary human hepatocytes and Kupffer cells and
tri-culture of primary human hepatocytes, Kupffer cells and stellate cells,
which are suitable for drug testing and cytotoxicity studies
3D HepaRG spheroids Cyprotex Scaffold-free multicellular native tissue-like models
DMPK, drug metabolism and pharmacokinetics; NASH, nonalcoholic steatohepatitis; DILI, drug-induced liver injury.

Volume 9 Issue 2 (2023) 210 https://doi.org/10.18063/ijb.v9i2.663