Reproducing organ interactions in body-on-chips

Abstract

Since the development of drugs has taken strides, the traditional ways of screening drugs using laboratory animals or 2D in vitro models have not been sufficient because of their lack of physiological relevance compared to humans. To overcome this problem, organ-on-chip technology was created.

Organ-on-chips are small microfluidic devices that have been designed to mimic a specific organ or tissue in the human body. Organ-on-chips are capable of mimicking environmental factors such as temperature, air composition and mechanical forces. Because organ-on-chips only include one organ, relevant interactions between organs cannot be mimicked. Since organs communicate with each other using molecules that are carried via the bloodstream, the interactions between organs are hard to examine in vitro. This challenge has led to the development of body-on-chip technology, with which the interactions between organs can be studied in a small scale.

By culturing different cell types in different compartments and connecting these compartments to each other, it is possible to mimic organ interactions in a small scale. Body-on- chips can be defined as microfluidic devices on which two or more cell types are cultured and connected to each other to create a part of the human body. Understanding these interactions in a small scale gives an insight of how drugs would ultimately affect humans in a larger scale.

Different compartments in body-on-chips can be connected to each other in various different ways. It is possible to use external connections such as tubing, when creating a body-on-chip from several organ-on-chips. To recapitulate organ interactions on a single chip, organ compartments can be connected by porous membranes on either planar or vertical orientation, or by microfluidic channels. The simplest way of constructing a body-on-chip is to connect several organ-on-chips by tubing or by a different external connection. Even though external connections are the simplest way of connecting organs to each other, the most common way of building a body-on-chip is to use microfluidic channels.

In order to communicate, organs need to have fluidic flow between each other to send signals. In the human body, this would be done by secreting molecules in the blood stream. In body-on-chips, organs communicate via cell culture media. Because there is no such thing as a universal medium yet, body-on-chips are forced to use several different cell culture medias in different parts of the chip to enable communicating and providing the cells with nutrients.

The future for body-on-chips is filled with challenges, from which maybe the biggest challenge is to develop a universal cell culture medium as efficient as blood in the human body. The universal cell culture medium would have to both mimic blood as accurately as possible and support all used cell types. It can be assumed that in the future body-on-chips will develop to recapitulate the human body even more accurately.