Drug induced liver injury (dili) is a leading cause for fda-approved drug withdrawal from the market and is the major health concern as more than 50 % of acute liver failures are caused by dili. current preclinical models inadequately predict hepatotoxicity and dili in humans. poor clinical translation arises from species differences present in animal models and the limited in vivo-relevant physiology of conventional liver cell culture. this not only leads to high preclinical and clinical attrition, but it can also pose serious health risks to patients. owing to the major limitations with animal models, regulatory and pharmaceutical communities are adopting dynamic in vitro human liver models for drug safety assessment, drug development, disease modeling and personalized medicine. the last 10 years witnessed significant advances in this field with growing interest from government regulatory agencies, and pharmaceutical companies. several initiatives such as fda modernization act 2.0, government of india's “new drugs and clinical trials (amendment) rules, 2023, nih-darpa tissue chip program, european organ-on-chip society (euroocs) and japanese agency for medical research and development (amed) mps program, has catalysed the development of several organ-on-chips companies. therefore, in order to cater to the immediate and cost-effective need in the development of human-relevant pre-clinical in vitro liver model, we have microengineered and validated {as per the central drugs standard control organisation (cdsco) and indian council of medical research (icmr) guidelines} a preclinical in vitro liver model using transdisciplinary technologies. in a landmark study in “biomaterials” journal (souradeep dey et. al, 2024), our team demonstrated that the developed human liver model could improve patient safety and reduce small-molecule clinical trial failures due to liver toxicity by up to 80%, with 100% specificity. in the reported study, utilizing 3d printing and microfluidic technology, we bioengineered a human physiomimetic liver model (hplm), recapitulating the radial hepatic cord-like structure with functional sinusoidal microvasculature network, biochemical and biophysical properties of native liver. intriguingly, the human derived hepatic cells incorporated hplm 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. overall, the microfluidic bioreactor-based hplm closely emulates in vivo like hepatic functionality and provides a useful platform for dili risk assessment with greater fidelity than animal testing or conventional cell culture, lowering the risk of dili and clinical trial attrition for drug candidates. the developed human physiomimetic 3d printed in vitro liver acinus model addresses patient-specific absorption, distribution, metabolism, excretion and toxicity (admet) and can serve as disease model platform for application related to therapeutic discovery and development, pathophysiological studies, precision medicine and pre-clinical trials. under the essence of “atmanirbhar bharat”, “biotechnology research innovation and entrepreneurship development (bio-ride)” and “biotechnology for economy, environment, and employment (bio-e3) schemes initiated by the government of india, we envision that our proposed technology holds high translational values in terms of technology transfer, product development and eventually commercializing the same through a start-up, for improving the current drug development scenario.