02282nas a2200325   4500000000100000000000100001008004100002260001200043100002300055700001700078700002000095700001600115700001600131700002300147700002800170700001800198700001700216700002600233700001700259700001500276700001400291700001700305700001800322245009100340856004800431300001100479490000700490520144500497022001401942       2020                            d  c2020-021 aAleksander Skardal1 aJulio Aleman1 aSteven Forsythe1 aShiny Rajan1 aSean Murphy1 aMahesh Devarasetty1 aNima Pourhabibi Zarandi1 aGoodwell Nzou1 aRobert Wicks1 aHooman Sadri-Ardekani1 aColin Bishop1 aShay Soker1 aAdam Hall1 aThomas Shupe1 aAnthony Atala00aDrug compound screening in single and integrated multi-organoid body-on-a-chip systems  uhttps://dx.doi.org/10.1088/1758-5090/ab6d36  a0250170 v123 aCurrent practices in drug development have led to therapeutic compounds being approved for widespread use in humans, only to be later withdrawn due to unanticipated toxicity. These occurrences are largely the result of erroneous data generated by in vivo and in vitro preclinical models that do not accurately recapitulate human physiology. Herein, a human primary cell- and stem cell-derived 3D organoid technology is employed to screen a panel of drugs that were recalled from market by the FDA. The platform is comprised of multiple tissue organoid types that remain viable for at least 28 days, in vitro. For many of these compounds, the 3D organoid system was able to demonstrate toxicity. Furthermore, organoids exposed to non-toxic compounds remained viable at clinically relevant doses. Additional experiments were performed on integrated multi-organoid systems containing liver, cardiac, lung, vascular, testis, colon, and brain. These integrated systems proved to maintain viability and expressed functional biomarkers, long-term. Examples are provided that demonstrate how multi-organoid ‘body-on-a-chip’ systems may be used to model the interdependent metabolism and downstream effects of drugs across multiple tissues in a single platform. Such 3D in vitro systems represent a more physiologically relevant model for drug screening and will likely reduce the cost and failure rate associated with the approval of new drugs.  a1758-5090