Question

Before drugs are tested on organisms, they are tested on cells and tissues, including cells in culture and organs on chips. Explain what features of organs on chips make them more suitable than cell culture for testing drugs

Answer 1

Answer:

The recent progress in the development of microfluidic-based systems including lab-on-a-chip (LOC) and multi-organs-on-a-chip. A plethora of microfluidic-based systems has been developed in the past few years with an ultimate aim to facilitate the predictive in vitro and in vivo models.

Moreover, comparative to traditional cell culture methods, i.e.,

(1) culture in flasks,

(2) culture in dishes and

(3) well-plates, etc.

microfluidics-based cell culture approach reveals a clear understanding of an interplay between cell culture parameters and the microenvironmental elements which traditional cell culture methods fail to demonstrate on their own.

The versatile multifunctional features of microfluidics—such as precise control over microenvironmental elements—opens up new avenues not only for tissue engineering areas but also for next-generation drug testing sectors. Furthermore, the notable capability of microfluidics to biomimetic the micron-scale structures along with fluidic manipulation under microenvironment demonstrates it to be a powerful tool to engineer products with multifunctional applications.

One of the most significant targets for research tools development is the human-on-a-chip to replace animal models in research test and pharmaceutical industry. The human-on-a-chip tool offers the opportunities for growth through the incorporation of more tissues with proper function and without external aid. For this proposal, a completely independent system requires that all tissue can adequately provide its physiological function.

First, it is needed to sustain cell viability for an extended time. The communication between tissues must offer a similar approach to the in vivo capacity, and not just by the microfluidic channels. For that, a high quantity of cell types must be developed, as shown by some of the presented works, where up to four cell types were grown from stem cells with the correct order and shape. Moreover, a proportional tissue, organ, volume, and whole mass must be sustained to provide a normal scaled human physiology.

In our opinion, a new trend would be to incorporate electrochemical biosensors in a human-on-a-chip platform to merge tools. This approach would add a new layer in research studies, allowing innovative experiments on processes such as cancer behavior, congenital diseases, brain function, tissue development, and differentiation.

As well as the correct physiology implementations, it is important to consider the design from a physics point of view; for example the inclusion of relevant parameters in the flow system and the biochemical equations. It is necessary to recognize the limitations of these in vitro models through their intrinsic value and exploit their benefits. Current research has been able to get closer to the idea of human-on-a-chip, and besides the mainstream of research for drug design and physiology, other novel applications are possible, including sensors development towards the detection of toxins, drugs, and hormones.

Through building a human reproductive tract it became possible to demonstrate that the biophysical environment helps sperm to reach the ovule. The cancer model is another critical issue, where an implementation of a human-on-a-chip has let researchers study metastasis, tumor growth, and its physiology. In summary, to fully elucidate and appreciate the potential of human-on-a-chip models as strategic measuring tools to test clinical trials on chips, correlations must be established between human in vitro measurements and traditional in vivo parameters.

This will also act as a bridge between conventional cell cultures and new standardized clinical trial procedures without using animal-based models.