way. The organ-on-a-chip as in vitro model will prove to be a potential platform
in the development of personalized medicines in future.
Keywords
In vitro model · Liver model · Kidney model · Lung model · Bioprinting · Human-
on-a-chip
6.1
Introduction
The pharmaceutical’s industry is the most demanding, and the most challenging
aspect is drug discovery that involves development, identification, characterization,
and optimization of new drug chemical entity (Hughes et al. 2011; Harper and Topol
2012). Several problems continually faced by drug developers related to adverse
effects of novel lead molecules and then to carry new drug candidate/entity on to the
market in a systematic and progressive manner (Bhusnure et al. 2017). In vitro
conventional cell models are generally used to examine and observe a variety of
signal molecules, viz., enzymes, receptors, and ligands, which are associated with
biological and physiological processes (Booth and Kim 2012). Nevertheless, there
are several drawbacks of conventional in vitro models like they do not mimic the
complexity of interactions of cells within the body. They do not detect the time-
changing signalling molecules (mechanical or chemical) due to its static conditions
and require excessive quantity of nutrients, which are vital for the normal cellular
functions (Frohlich et al. 2013; Griep et al. 2013; Polini et al. 2019). Further, these
models do not imitate the extracellular mechanical environment (Bhusnure et al.
2017).
Due to the poor predictive power of existing animal models used in preclinical
research, several proposed drug molecules fail in clinical studies during the new drug
research and discovery process. This problem arises due to the use of conventional
animal testing models that only detect the investigational drugs in animals and in
human cells. In addition, another complexity comes from the genetic variability
among patients that can change the pharmacokinetic and pharmacodynamic
behaviour to a drug.
Thus, there is always an urgent demand by the pharmaceutical companies in the
development of novel testing approaches, to produce the authentic and reliable
information of drug candidate w.r.t. its safety and toxicity profile clinically in
human beings. To overcome these challenges, microfabrication and microfluidics
based on micro-engineered cell culture models are used nowadays. Development of
advanced cell culture models opens a new era in the drug discovery, i.e. organ-on-a-
chip, which is a more reliable and precise approach in the human biological
processes and can transfigure the outlook of drug development process and methods
(Esch et al. 2015). This advanced technique when compared to conventional models
assist for the selection of right drug molecule and its concentrations in a time
efficient manner (Booth and Kim 2012). Moreover, they can generate different
74
G. Aggarwal et al.