mechanical/chemical stimuli and its concentration gradients of all signalling

molecules that can be applied electronically in a time-controlled manner. Nowadays,

pharmaceutical industry focussing on the latest advancement in the development of

the newest microdevices and bio-microelectromechanical systems (BioMEMS),

collectively known as ‘organ-on-chips’. The ‘organ-on-chip’ has shown its potential

to bridge the difference between preclinical to clinical studies. It can enumerate the

complexity between cell-to-cell interactions, providing cellular micro-environment

in a time-controlled manner, and signals are transmitted into the cellular constructs

with high precision (Frohlich et al. 2013; Griep et al. 2013; Jang and Suh 2010;

Polini et al. 2014; Chen et al. 2012).

On the other hand, 2D/conventional cell culture simulations do not provide

information about the structural complexity within and outside the cells in a consis-

tent and realistic manner. Organ-on-chips make the best selection possible by

utilizing 3D cell culture versions due to their superior capability to imitate tissue

design, structure, and function (Chen et al. 2012). Gap junctions, which are required

for cell-to-cell information exchange, tissue integrity, and architecture, are also more

prevalent in 3D. Further, 3D cell culture is fully grown and binds compactly to cells,

preventing or decreasing drug diffusion and permeability, which is not possible in

2D cell culture models. Thus, 3D cell culture models such as organ-on-a-chip are

more capable in microfluidics than 2D cell models when it comes to the discovery of

new drug molecules and their associated studies (Guido et al. 2011; Arrowsmith and

Miller 2013).

This chapter looks at how rapid advances in ‘3D bioprinting’ of tissues and

organs, particularly ‘organ-on-a-chip’ in vitro technologies, have opened new

possibilities for improving human condition modelling. It discusses that organ-on-

chip-based 3D models can be a possible replacement for animal modelling and might

be helpful in the transition of conventional preclinical techniques and models into

novel research and brings a new platform in the modern drug research for developing

in a cost- and time-effective manner. In the chapter, development and applications of

various organ-on-chips are discussed along with challenges in the use of these novel

in vitro models.

6.2

Potential of In Vitro Biological Models in Drug Discovery

Drug discovery process is a time-consuming and costly process. Several drugs fail

during clinical trials (phase 2 and phase 3) due to its low pharmacological efficacy

profile and its safety concern, i.e. inadequate therapeutic index (Langhans 2018).

Currently used preclinical models in drug discovery do not provide better precision

data, and hence, attrition rate is high during development of new lead molecules.

There is always a need to consider new technologies/testing models with enhanced

precision in the process of drug development. In vitro models are found to be crucial

in drug research because they provide insight into the behaviour of cells and

microorganisms. Conventional in vitro models may not be able to forecast the impact

6

Organ-on-a-Chip: Novel In Vitro Model for Drug Discovery

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