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.
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Hornberg JJ , et al.
Exploratory toxicology as an integrated part of drug discovery. Part I: Why and how. - PubMed - NCBI
Developmentally inspired human 'organs on chips'. - PubMed - NCBI
Kinter LB and DeGeorge JJ
Scientific Knowledge and Technology, Animal Experimentation, and Pharmaceutical Development. - PubMed - NCBI
Olson H , et al.
Concordance of the toxicity of pharmaceuticals in humans and in animals. - PubMed - NCBI
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5 August 2017
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