in the alveoli during respiratory movement. In fact, the mechanical forces increased
tissue permeability three times over that time in combination with IL-2. Additional
research revealed that IL-2 successfully inhibited vascular leakage completely when
given with angiotensin-1 (Xu et al. 2013).
The ‘lung-on-a-chip’ model for asthma and chronic obstructive pulmonary dis-
ease (COPD) was used to substantiate claims that tofacitinib, a medication employed
to treat rheumatoid arthritis, could suppress lung inflammation. Additionally, it was
discovered that inhibiting neutrophil adhesion with a bromodomain-containing
protein 4 (BRD4) inhibitor could reduce lung infection by nearly 75% under
complex flow conditions (Benam et al. 2016).
6.6.2
Liver-on-a-Chip
The liver has a multitude of roles, such as protein synthesis, hormonal balance,
glycogen storage, and detoxification. It is an important toxicity target in human drug
interactions as well as a player in the drug induction. The liver is extremely active in
metabolism and thus essential to life. Metabolic activity in the liver is very high, and
without it, we would not have a metabolism. Besides its amazing regenerative
capabilities, chronic diseases and viral infections cause significant damage to tissue,
as well. Hepatocytes are tied together by blood vessels and Kupffer cells into the
hepatic lobule, which performs all the major functions of the liver. Hepatocytes are
difficult to keep alive in the lab. Hepatic cell microsphere system was specifically
created to study hepatic interactions in 3D cultures. Other experimentation that may
be conducted includes but is not limited to drug testing, pathogenesis, human
physiology, and toxicity, and screening with a liver-on-chip (Dixon et al. 2018).
The liver is used in human and animal models to study the metabolic rate and
toxicity of chemicals and medications, as well as to assess the efficacy of treatments.
Primary cells are obtained from patients or cell banks, such as the ‘American Tissue
Culture Collection’, and subjected to a battery of tests to determine whether they
exhibit the properties of human tissue when cultured. They may use cell cultures to
better understand how drugs move through the body. The ability to discover new
drugs is harmed when normal human liver cell activities such as transport and drug
breakdown are lost in cell culture. Liver-on-chip systems have been proposed as a
new generation of in vitro drug screening models. Some liver-on-chip systems
include biophysically preprefigured or 3D bio-printed matrices to enable 3D organ
building (Bhatia and Ingber 2014; Miranda et al. 2021).
On the one hand, hepatology research and drug discovery depend on in vitro
models of the liver. An essential part of these models is the cell source. Human,
animal-derived, and hep-derived stem cells are the three major cell types employed
to generate real liver tissue in the laboratory. Researchers currently utilise a variety
of human hepatic cell outlines like hepatocytes, sinusoidal endothelial (Hep2), and
hepatic stem cells for toxicological assessments (HepaRG). Hepatocytes are the
liver’s parenchymal cells that help maintain liver functions, making them the most
active cells in the lobules. Also known as the reticuloendothelial, the system, the
6
Organ-on-a-Chip: Novel In Vitro Model for Drug Discovery
83