Approaching the in vitro clinical trial: engineering organs on chips

Abstract

In vitro cell culture and animal models are the most heavily relied upon tools of the pharmaceutical industry. When these tools fail, the results are costly and have at times, proven deadly. One promising new tool to enhance preclinical development of drugs is Organs on Chips (OOCs), proposed as a clinically and physiologically relevant means of modeling health and disease. Bringing the patient from bedside to bench in this form requires that the design, build, and test of OOCs be founded in clinical observations and methods. By creating OOCs as models of the patient, the industry may be better positioned to evaluate medicinal therapeutics.

Figure 1

A depiction of the Design, Build, and Test algorithm as applied to the engineering of a Brain-on-Chip device. The OOC “blueprint” should illustrate the spatiotemporal arrangements of cells, then determine the dynamic architecture of the tissue, and finally understand the necessary organ systems to be included for physiologically relevant PK/PD. The build of an OOC must focus on defining the tools and materials from which the chips is build: ensuring the cell building blocks and 3D architecture in which they are assembled mimics that of the patient. The test of an OOC must likewise be inspired by the patient.

Figure 2

A comparison of various clinical function tests used for diagnostics against the typical readouts that are possible with Organ-on-Chip technologies for the Brain, Heart, Liver and Intestines. Although some OOC readouts can be related to functional tests (as with the Liver), the majority lack a firm relationship with a corresponding clinical diagnostic technique.