Abstract

Multi-Organ Interconnected Human-on-a-Chip Systems to Develop Phenotypic Disease Models For In Vivo Predictions

James Hickman, Professor, University of Central Florida

I will describe such systems being constructed that are guided in their design by PBPK models. They are “self-contained” in that they can operate independently and do not require external pumps as is the case with other microphysiological systems. They are “low cost”, in part, because of the simplicity and reliability of operation allowing the observation of the effects of not only drugs but their metabolites. While systems can be sampled to measure the concentrations of drugs, metabolites, or biomarkers, they also can be interrogated in situ for functional responses such as electrical activity, force generation, or integrity of barrier function. Operation up to 28 days has been achieved allowing observation of both acute and chronic responses with serum free media. We have worked with various combinations of internal organ modules (liver, fat, neuromuscular junction, skeletal muscle, cardiac, bone marrow, blood vessels and brain) and barrier tissues (e.g. skin, GI tract, blood brain barrier, lung and kidney) and immune components. The use of microelectrode arrays to monitor electrically active tissues (cardiac and neuronal) and micro cantilevers (muscle) have been demonstrated. Most importantly, these technical advances allow prediction of both a drug’s potential efficacy and toxicity (side-effects) in pre-clinical studies.