Research Projects

Drug-induced liver injury (DILI) is a multifactorial and patient-specific adverse reaction to drugs or xenobiotics, often leading to the loss of both parenchymal and non-parenchymal liver cells. Despite regulatory mandates by the US FDA, EMA, and CDSCO India for preclinical evaluation using animal models, only ~55% concordance is observed between animal and human hepatotoxic outcomes. This limited predictability arises from interspecies differences in liver architecture, drug metabolism, transporter expression, and immune responses, underscoring the urgent need for more physiologically relevant in vitro human liver models that align with the 3Rs principle (Reduction, Replacement, Refinement). While conventional in vitro liver cultures are cost-effective, they lack the native liver’s architecture, mechanical cues, and dynamic environment. Microfluidic liver models, with their ability to simulate tissue-level function, vascular perfusion, metabolic gradients, and multicellular interactions, offer improved prediction of drug toxicity and disease progression. Additionally, hepatotropic infections like hepatitis and malaria represent critical health challenges. These pathogens exploit liver-specific biology, where hepatitis viruses cause chronic liver inflammation and fibrosis, while Plasmodium sporozoites replicate in hepatocytes and release merozoites in the bloodstream. Studying these infections demands advanced physiomimetic models to dissect host-pathogen interactions, immune dynamics, and antiviral or antiparasitic drug efficacy in a controlled, human-relevant system. Building on Prof. Biman B. Mandal’s expertise in tissue engineering, his group has developed a physiomimetic microfluidic liver model that mimics native human liver microarchitecture and function. In the proposed project, the first phase will focus on miniaturizing this model to enable high-throughput drug screening. Using iterative design and computational simulation, an optimized microfluidic bioreactor will be developed. Further, a 3D-printed liver acinus-mimetic model, fabricated with an optimized biomaterial ink, will be incorporated with both parenchymal and non-parenchymal hepatic cells and cultured under perfused conditions. Further, functionality will be assessed through hepatic biomarkers, secretome analysis, and gene expression profiling. The second phase of the study involves validation of the liver model for high-throughput screening applications against hepatotoxicants, non-hepatotoxicants, and idiosyncratic drugs. Additionally, an attempt will also be made to study hepatotropic infection in the model such as hepatitis or malaria, enabling evaluation of host-parasite interactions, hepatocyte response and drug efficacy. Collaboratively conceptualized with Prof. Biman B. Mandal, this project aims to establish physiomimetic microfluidic liver models as advanced preclinical tools for drug development and infectious disease research.