6.6

Development and Usage of Various Types

of Organ-on-Chip Technologies in Drug Discovery

6.6.1

Lung-on-a-Chip

In humans, lungs are the main part of lower respiratory system. The composition of

lungs includes airways, branched blood vessels, conducting zone (air entry zone),

and respiratory zone (zone for exchange of oxygen and carbon dioxide). The

respiratory parts include bronchus, bronchiole, and alveoli. The smallest unit of

lung is the alveolus, which is functional and provides a sufficient surface area for gas

exchange. The creation of tissue of lungs is challenging but can help to understand

the effect of new drugs, toxins, and pathogens in airways and mechanism of

infectious diseases affecting the respiratory function (Benam et al. 2016; Zepp and

Morrisey 2019).

In this area of research, the microfluidic lung-on-a-chip device was developed by

Harvard scientists at the ‘Wyss Institute for biologically inspired engineering’. It

incorporated the flow of lung fluid and breathing patterns like those of a human-on-

a-microchip. The membrane was permeable between two distinct layers of lung

cells, with separate upper and lower canals between them. For cyclic mechanical

breathing, the chambers were evacuated to get a greater range of motion and stretch.

It was demonstrated that the ‘alveolus-on-a-chip’ or ‘lung-on-a-chip’ can be used to

conduct experiments on natural breathing, and it can be used to understand the safety

and efficacy of new dosage forms like nanoparticles. It is also possible to do

experiments on new and novel types of drugs and lung cancers. Asthmatic and

non-asthmatic bronchial epitheliums were grown on the air/non-asthmatic cells,

respectively, to create 3D models of asthmatic and non-asthmatic tissue (Huh et al.

2012).

The Wyss Institute worked on several microchips to inspect the capillary-alveolar

membrane system of the human lung (Huh et al. 2010). It was experimented with a

variety of configurations, one of which used a living alveolar-capillary unit. Mim-

icking the human’s lung’s functional alveolar unit, the biomimetic microsystem was

developed to assess the effectiveness of drugs (Jain et al. 2018).

A thin alveolar septum, built on a bioengineered ‘lung-on-a-chip’, was freshly

found to be capable of accurately reproducing lung dynamic respiratory complexity.

As one can see, the main goal of lung tissue regeneration is to help to grow epithelial

and endothelial cells in an environment that simulates human respiration. The

researchers showed that involuntary stress affects the epithelial wall porousness

using a bronchial epithelial cell line. Furthermore, the cell culture outperformed a

static model, it can mimic the lungs, and it helps in explaining how the lungs work

and can be used to simulate pulmonary disease. Results revealed that toxicity testing

and a new drug development are also possible using this micro-device (Stucki et al.

2015).

A drug development study made use of the model, resulting in finding out the

effect of interleukin during pulmonary oedema in patients. Research has shown that

intercellular junctions are opened synergistically with the endothelial-lung junctions

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