The primary goal of organ-on-a-chip (aka tissue-on-a-chip) technology is to accurately mimic in vivo biology so that safer and more effective medicines can be discovered faster.
Lack of drug safety is the major factor contributing to the >90% overall failure rate during the drug development process and the liver is the most problematic organ with regards to toxicity issues.
This high drug attrition rate is primarily a result of the poor ability of animal studies to predict drug-induced liver injury (DILI), with 57% of human hepatoxicities being unobservable in rodents and 37% unobservable in non-rodents.
Animal drug testing is slow and resource intensive, often requiring numerous separate rounds of drug scale-up to supply animal studies throughout the lead optimization phase. With an average of 2,700 rodents and 300 non-rodents being used for each single successful drug registration (and keeping in mind that 9 out of 10 potential registrations fail), the animal usage, cost, and inefficiencies in the drug development process are staggering.
Organ-on-a-chip models are poised to offer solutions to these major problems through the replication of human biology and with the potential to be high-throughput in vitro drug screening platforms. The approach of the technology involves the growth of cells in distinct compartments within a microfluidics device that are networked to each other through embedded channels. Cell media ("blood") flows through such channels and is circulated to each compartment on the chip, enabling cross-talk between different tissue types. The rate of media flow is typically controlled by pneumatic pumps and advanced bioengineering approaches can enhance cellular maturation in order to induce a more physiologically relevant organ-like phenotype. As an example, native organ biology such as gut peristalsis or breathing of the lungs can be mimicked with vacuum controlled stretching and contracting of the chips.
Concordance of the toxicity of pharmaceuticals in humans and in animals. - PubMed - NCBI
Olson H , et al.
Developmentally inspired human 'organs on chips'. - PubMed - NCBI
Exploratory toxicology as an integrated part of drug discovery. Part I: Why and how. - PubMed - NCBI
Hornberg JJ , et al.
5 August 2017
Scientific Knowledge and Technology, Animal Experimentation, and Pharmaceutical Development. - PubMed - NCBI
Kinter LB and DeGeorge JJ