02377nas a2200289   4500000000100000008004100001260001500042653001600057653003700073653003000110653001900140653001900159653002200178653003800200100001800238700001700256700001400273700002100287700002100308700002000329245010300349856007200452300001100524490000800535520153000543022001402073       2024                            d  c2024-10-0110a3D printing10aCell instructive biomaterial ink10aDrug induced liver injury10aDrug screening10aHepatotoxicity10aHuman liver model10aPhysiomimetic microfluidic device1 aSouradeep Dey1 aAmritha Bhat1 aG. Janani1 aVartik Shandilya1 aRaghvendra Gupta1 aBiman B. Mandal00aMicrofluidic human physiomimetic liver model as a screening platform for drug induced liver injury  uhttps://www.sciencedirect.com/science/article/pii/S0142961224001613  a1226270 v3103 aThe pre-clinical animal models often fail to predict intrinsic and idiosyncratic drug induced liver injury (DILI), thus contributing to drug failures in clinical trials, black box warnings and withdrawal of marketed drugs. This suggests a critical need for human-relevant in vitro models to predict diverse DILI phenotypes. In this study, a porcine liver extracellular matrix (ECM) based biomaterial ink with high printing fidelity, biocompatibility and tunable rheological and mechanical properties is formulated for supporting both parenchymal and non-parenchymal cells. Further, we applied 3D printing and microfluidic technology to bioengineer a human physiomimetic liver acinus model (HPLAM), recapitulating the radial hepatic cord-like structure with functional sinusoidal microvasculature network, biochemical and biophysical properties of native liver acinus. Intriguingly, the human derived hepatic cells incorporated HPLAM cultured under physiologically relevant microenvironment, acts as metabolic biofactories manifesting enhanced hepatic functionality, secretome levels and biomarkers expression over several weeks. We also report that the matured HPLAM reproduces dose- and time-dependent hepatotoxic response of human clinical relevance to drugs typically recognized for inducing diverse DILI phenotypes as compared to conventional static culture. Overall, the developed HPLAM emulates in vivo like functions and may provide a useful platform for DILI risk assessment to better determine safety and human risk.  a0142-9612