In Aim 1, we developed a unique microarray 3D bioprinting protocol of progenitor cells in biomimetic hydrogels on a pillar plate with sidewalls and slits, coupled with a clear bottom, 384-deep well plate for scale-up production of human liver organoids (HLOs). The pillar plate platform streamlines the process of organoid differentiation and compound screening by enabling rapid loading through printing and culture media change with minimal human interventions. In Aim 2, human iPSC-derived expandable HLOs were generated, which can be passaged and cryopreserved. Additionally, differentiated HLOs (diff-HLOs) were generated by optimizing differentiation protocols and using the pillar/perfusion platform, resulting in enhanced maturity and functionality. Furthermore, in situ drug testing assessments were performed using day-20 diff-HLOs cultured on the pillar/perfusion platform, along with a study on liver regeneration post-injury. Among adverse drug reactions in the liver, drug-induced liver injury (DILI) is one of the frequent causes of safety-related drug withdrawals from the market. In Aim 3, we aimed to model poor and ultrafast metabolizers caused by ethnicity-based genetic polymorphisms to study DILI. Here, we used the CRISPRai system to activate and inhibit the expression of drug metabolizing enzymes (DMEs), thereby simulating up-regulation and down-regulation to recapitulate the activity levels observed among various ethnic groups.