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International Journal of Bioprinting New challenges in liver tissue engineering

limited by the scarcity of organs. On the other hand, both trends are constantly changing, and the incidence of
2
animal models and the traditional cell-based systems often viral liver disease will probably be reduced in the future
fail to adequately recapitulate human pathophysiology, following the vaccination efforts and implementation of
a conundrum that hinders the development of suitable new treatments, while the incidences of drug-induced
treatments and accounts for the limited number of liver injury (DILI) and MASLD are expected to increase in
currently available therapies. 3 Western countries. 10
Several cell-based models have been proposed to study Alcohol consumption is a risk factor associated with
liver physiology and disease development. The traditional multiple diseases, including cirrhosis and cancer. There is
1
in vitro systems featuring monolayer cultures of primary an exponential correlation between alcohol consumption
1,11
human hepatocytes (PHHs) or hepatoma cell lines are still and the development of cirrhosis, but it is also important
4
the predominant mode of research in this field, but the to take into account the synergic effect of alcohol and
new, more complex systems that consider that the three- other factors such as obesity or infection in developing
dimensional (3D) organization have been on the rise, along the disease. Alcoholic liver disease encompasses a range
12
with the fact that many different liver cell types contribute of liver pathologies, such as steatosis, liver injury, and
to hepatic functionality and participate in the development inflammatory infiltrate, which usually appear associated
of diseases have been increasingly described. In this regard, to fibrosis and can progress to HCC. Histologically,
13
the central objective of liver tissue engineering is to create cirrhosis, which can also be precipitated by produced other
models that mimic the in vivo liver functions. These models diseases, e.g., hepatitis, causes an expansion of the ECM
can be applied to unravel the mechanisms of different and the capillarization of the endothelium.
14
liver pathologies and to treat liver disorders. In these MASLD is characterized by excessive lipid accumulation
engineering approaches, both the cellular components in the liver and can range from simple steatosis to
and the extracellular matrix (ECM) organization that best steatohepatitis, also characterized by inflammation and
reflect what happens in vivo should be considered.
necrosis of hepatocytes and fibrosis. Hepatic fibrosis
15
Different biomaterials have been used in liver tissue is defined as the accumulation of ECM proteins in the
engineering to provide a suitable microarchitecture, space of Disse that can even block the blood flow. In liver
16
composition, and stiffness, among other attributes. Finally, fibrosis, in response to chronic liver injury, hepatic stellate
5
in recent decades, bioprinting has appeared as a method cells (HSCs) are activated into proliferative fibrogenic
of increasing the throughput of the test systems that best fibroblasts, and several inflammatory mediators are
mimic the environment and complexity of liver tissue. 6 upregulated, eventually resulting in ECM accumulation
17
In this paper, we review the advanced materials used and progressive fibrosis. The progression of steatohepatitis
15,18
as hydrogels or scaffolds for 3D liver models, especially underlies cirrhosis and even HCC. Different genetic,
focusing on the cell type(s) used, since different cells can dietary, metabolic, and immunological factors have
been implicated in MASLD.
Currently, there is no
15,18
be used for in vitro models. We also provide an overview pharmacological therapy available, and the variation in
of the use of these strategies for drug screening, disease lifestyle is the commonest therapeutic indication. 19
modeling, or regenerative medicine, indicating the
challenges that need to be solved. Hepatitis B and C infections represent one of the
primary factors for liver disease development in Europe.
1
2. Liver disease and treatment The pathogenesis of hepatitis B and C viral infections is
generally mediated by the immune system, even though
2.1. Liver disease
The liver has an extraordinary ability to restore its mass both viruses can avoid immune removal and continue to
after loss or injury, and liver regeneration has been shown replicate in the infected host for years. Chronic infection
7
20
to combine both hepatocyte proliferation (hyperplasia) and can result in oxidative stress induction and inflammation.
hypertrophy, although certain conditions such as chronic Vaccination programs have brought significant
8
liver injury can impair its regenerative properties. Acute improvements to the reduction of advanced liver disease
9
incidence caused by hepatitis B virus, but achieving
and chronic liver diseases are major reasons of mortality complete eradication of the disease remains a monumental
worldwide, accounting for approximately 2 million deaths 21
per year, and pose a considerable economic problem. The task. On the other hand, hepatitis C is the leading cause
main causes of liver disease are viral hepatitis, MASLD, of HCC, although antiviral therapies have reduced the
21
and alcoholic liver disease. Others include primary burden of hepatitis C viral infection.
1,10
cholangitis, autoimmune hepatitis, and inherited metabolic HCC is the most common type of primary liver cancer
10
disorders such as alpha-1-antitrypsin deficiency. These that is often linked to other chronic liver diseases such as
Volume 10 Issue 3 (2024) 117 doi: 10.36922/ijb.2706