Advanced engineered tissues for replicating first pass metabolism on chip

In this work, we developed an innovative gut-liver-on-chip system useful to predict oral drug administration and first pass metabolism. The two main organs involved in the first pass metabolism are the liver and the intestine. First-pass effects consist mainly in the reduction of bioavailability of drugs and xenobiotics. The prediction of this mechanism is important both for the development of new substances, but also for toxicity testing. For this purpose, we designed a microfluidic device which interconnect 3D human intestinal equivalent (3D-HIE) and HepG2-microtissues, recapitulating the intestinal and hepatic firstpass effect mechanism of ethanol. 3D-HIE were obtained by bottom up approach, using intestinal microtissues moulded into a maturation chamber and HepG2-μTPs were obtained by dynamic cell seeding of Hepg2 and gelatin porous microsphere in a spinner flask bioreactor.