Liver-on-a-Chip (LoC) Models: Case Studies of Academic Platforms and Commercial Products.

Pharmaceutical companies place significant importance on the liver due to its crucial role in numerous biochemical processes, specifically in drug metabolism. This focus has led to significant progress in liver-on-a-chip (LoC) technology, which has proven useful not only in drug development but also in more advanced applications. As a result, elaboration and incorporation of advanced LoC models into preclinical workflows have great potential to decrease R&D expenses and reduce or even replace animal testing, while improving the safety and efficacy of new therapies. To explore this potential, the present review provides an overview of recent academic and commercial LoC models, examines their different designs and cellular compositions, and evaluates the advantages and disadvantages of their complexity. A systematic comparison of these models is then performed, along with a discussion of their current challenges and future perspectives. Ultimately, we hope this review will assist scientists and industry professionals in selecting optimal models and in contributing to future advancements in LoC technology.

• Publication year

  2026

• Venue

  Molecular Pharmaceutics

• Publication date

  2026-02-01

• Fields of study

  Medicine, Engineering

• Identifiers
  DOI 10.1021/acs.molpharmaceut.5c01122PMID 41622665PMCID PMC12958302
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Pathophysiology of liver cirrhosis and risk correlation between immune status and the pathogenesis of hepatocellular carcinoma

  2025cited by this paper
• Global burden of cirrhosis and other chronic liver diseases caused by specific etiologies from 1990 to 2021

  2025cited by this paper
• Revolutionizing drug evaluation system with organ-on-a-chip and artificial intelligence: A critical review

  2025cited by this paper
• Development of an AI model for DILI-level prediction using liver organoid brightfield images

  2025cited by this paper
• Mass fabrication of PDMS microfluidic devices by injection molding and applications in sensitive 3D spheroid and explant culture

  2025cited by this paper
• An Immune-Liver Microphysiological System Method for Evaluation and Quality Control of Hepatotoxicity Induced by Polygonum multiflorum Thunb. Extract.

  2025cited by this paper
• Artificial intelligence in preclinical research: enhancing digital twins and organ-on-chip to reduce animal testing.

  2025cited by this paper
• Supervised-Learning-Driven Interrogation of Organ-on-a-Chip Quality from Microscopy Images

  2025cited by this paper
• Modeling of lung-liver interaction during infection in a human fluidic organ-on-a-chip

  2025cited by this paper
• Evaluating the synergistic use of advanced liver models and AI for the prediction of drug-induced liver injury

  2025cited by this paper
• Design and optimization of electrode-integrated microfluidic chips for enhanced electrochemical impedance spectroscopy assessments

  2025cited by this paper
• Advances in 3D Bioprinting and Microfluidics for Organ-on-a-Chip Platforms

  2025cited by this paper
• Advanced liver-on-chip model mimicking hepatic lobule with continuous microvascular network via high-definition laser patterning

  2025cited by this paper
• Low dose of micro-/nano-plastics mixture induced cardiac hypertrophy and reductive stress: The liver-heart crosstalk and hepatic-cardiac organoids-on-a-chip.

  2025cited by this paper
• On‐Chip Differentiation of Hepatic Cords with Radial Flow

  2024cited by this paper
• From Organ-on-a-Chip to Human-on-a-Chip: A Review of Research Progress and Latest Applications.

  2024cited by this paper
• High‐Scale 3D‐Bioprinting Platform for the Automated Production of Vascularized Organs‐on‐a‐Chip

  2024cited by this paper
• Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

  2024cited by this paper
• Metabolic-Associated Fatty Liver Disease: The Influence of Oxidative Stress, Inflammation, Mitochondrial Dysfunctions, and the Role of Polyphenols

  2024cited by this paper
• DigiLoCS: A leap forward in predictive organ-on-chip simulations

  2024cited by this paper
• Translational research on drug development and biomarker discovery for hepatocellular carcinoma

  2024cited by this paper
• Clinical Perspectives and Novel Preclinical Models of Malignant Pleural Mesothelioma: A Critical Review.

  2024cited by this paper
• Regular Consumption of Green Tea as an Element of Diet Therapy in Drug-Induced Liver Injury (DILI)

  2024cited by this paper
• The Application of Convolutional Neural Networks in Organ-on-a-Chip Technology: A Review

  2024cited by this paper
• A hollow fiber membrane-based liver organoid-on-a-chip model for examining drug metabolism and transport

  2024cited by this paper
• Convenient rapid prototyping microphysiological niche for mimicking liver native basement membrane: Liver sinusoid on a chip.

  2024cited by this paper
• Pump‐Less, Recirculating Organ‐on‐Chip (rOoC) Platform to Model the Metabolic Crosstalk between Islets and Liver

  2024cited by this paper
• Electrosprayed MnFe2O4/PVDF membrane integrated microfluidic chip for amoxicillin removal with real-time monitoring of pH and dissolved oxygen

  2024cited by this paper
• In Vitro Hepatotoxicity of Routinely Used Opioids and Sedative Drugs

  2024cited by this paper
• A novel green Microfiltration approach by developing a Lab-on-a-Chip System: A case study for Escherichia coli

  2024cited by this paper
• Construction of in vitro liver-on-a-chip models and application progress

  2024cited by this paper
• Organ-On-A-Chip (OOC) Image Dataset for Machine Learning and Tissue Model Evaluation

  2024cited by this paper
• Liver-on-chips for drug discovery and development

  2024cited by this paper
• Grand challenges in organoid and organ-on-a-chip technologies

  2024cited by this paper
• 3D microperfusion of mesoscale human microphysiological liver models improves functionality and recapitulates hepatic zonation.

  2023cited by this paper
• Detection of lineage-reprogramming efficiency of tumor cells in a 3D-printed liver-on-a-chip model

  2023cited by this paper
• Reproducibility and Robustness of a Liver Microphysiological System PhysioMimix LC12 under Varying Culture Conditions and Cell Type Combinations

  2023cited by this paper
• Microneedle array facilitates hepatic sinusoid construction in a large-scale liver-acinus-chip microsystem

  2023cited by this paper
• Improvements in Maturity and Stability of 3D iPSC-Derived Hepatocyte-like Cell Cultures

  2023cited by this paper
• Organ-on-a-chip meets artificial intelligence in drug evaluation

  2023cited by this paper
• Cholangiocarcinoma-on-chip: A 3D liver tumor platform for personalized medicine

  2023cited by this paper
• High-throughput microfluidic chip with silica gel‐C18 channels for cyclotide separation

  2023cited by this paper
• Evolving considerations for choice of hepatitis B vaccine.

  2023cited by this paper
• Drug discovery and development: introduction to the general public and patient groups

  2023cited by this paper
• LivHeart: A Multi Organ‐on‐Chip Platform to Study Off‐Target Cardiotoxicity of Drugs Upon Liver Metabolism

  2023cited by this paper
• Recent Advances of Biosensor-Integrated Organ-on-a-Chip Technologies for Diagnostics and Therapeutics.

  2023cited by this paper
• A review of complex in vitro cell culture stressing the importance of fluid flow and illustrated by organ on a chip liver models

  2023cited by this paper
• A biomimetic liver cancer on-a-chip reveals a critical role of LIPOCALIN-2 in promoting hepatocellular carcinoma progression

  2023cited by this paper
• Author Correction: Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology

  2023cited by this paper
• Microfluidic Liver-on-a-Chip for Preclinical Drug Discovery

  2023cited by this paper
• Clamping strategies for organ-on-a-chip devices

  2023cited by this paper
• Global burden of Liver Disease: 2023 Update.

  2023cited by this paper
• 3D-bioprinted cholangiocarcinoma-on-a-chip model for evaluating drug responses

  2023cited by this paper
• Integration of Extracellular Matrices into Organ‐on‐Chip Systems

  2023cited by this paper
• Development of an Induced Pluripotent Stem Cell-Based Liver-on-a-Chip Assessed with an Alzheimer’s Disease Drug

  2023cited by this paper
• Coculture model of a liver sinusoidal endothelial cell barrier and HepG2/C3a spheroids-on-chip in an advanced fluidic platform.

  2023cited by this paper
• The evolving role of investigative toxicology in the pharmaceutical industry

  2023cited by this paper
• Vascular traffic control of neutrophil recruitment to the liver by microbiota-endothelium crosstalk.

  2023cited by this paper
• Application of a skin and liver Chip2 microphysiological model to investigate the route‐dependent toxicokinetics and toxicodynamics of consumer‐relevant doses of genistein

  2023cited by this paper
• Researchers and regulators plan for a future without lab animals

  2023cited by this paper
• Emerging trends in organ-on-a-chip systems for drug screening

  2023cited by this paper
• From Single- to Multi-organ-on-a-Chip System for Studying Metabolic Diseases

  2023cited by this paper
• Human induced pluripotent stem cell–derived liver-on-a-chip for studying drug metabolism: the challenge of the cytochrome P450 family

  2023cited by this paper
• Increased sinusoidal pressure impairs liver endothelial mechanosensing, uncovering novel biomarkers of portal hypertension

  2023cited by this paper
• Development of a lung-liver in vitro coculture model for inhalation-like toxicity assessment.

  2023cited by this paper
• A Novel Milli-fluidic Liver Tissue Chip with Continuous Recirculation for Predictive Pharmacokinetics Applications

  2023cited by this paper
• Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding

  2023cited by this paper
• A Human Stem Cell-Derived Brain-Liver Chip for Assessing Blood-Brain-Barrier Permeation of Pharmaceutical Drugs

  2022cited by this paper
• Design and Fabrication of a Liver-on-a-chip Reconstructing Tissue-tissue Interfaces

  2022cited by this paper
• Constructing biomimetic liver models through biomaterials and vasculature engineering

  2022cited by this paper
• Perspectives on the evaluation and adoption of complex in vitro models in drug development: Workshop with the FDA and the pharmaceutical industry (IQ MPS Affiliate).

  2022cited by this paper
• On chip microfluidic separation of cyclotides

  2022cited by this paper
• A guide to the organ-on-a-chip

  2022cited by this paper
• Liver-on-a-chip: Considerations, advances, and beyond.

  2022cited by this paper
• Applied Hepatic Bioengineering: Modeling the Human Liver Using Organoid and Liver-on-a-Chip Technologies

  2022cited by this paper
• An Overview of Organs-on-Chips Based on Deep Learning

  2022cited by this paper
• Three-Dimensional-Bioprinted Liver Chips and Challenges

  2022cited by this paper
• Liver Acinus Dynamic Chip for Assessment of Drug-Induced Zonal Hepatotoxicity

  2022cited by this paper
• A rodent thyroid-liver chip to capture thyroid toxicity on organ functional level.

  2022cited by this paper
• Mimicking Native Liver Lobule Microarchitecture In Vitro with Parenchymal and Non-parenchymal Cells Using 3D Bioprinting for Drug Toxicity and Drug Screening Applications.

  2022cited by this paper
• In Vitro Models for the Study of Liver Biology and Diseases: Advances and Limitations

  2022cited by this paper
• State-of-the-art liver disease research using liver-on-a-chip

  2022cited by this paper
• Liver zonation, revisited

  2022cited by this paper
• Liver-on-a-Chip devices: The Pros and Cons of Complexity.

  2022cited by this paper
• Oxygen Gradient Induced in Microfluidic Chips Can Be Used as a Model for Liver Zonation

  2022cited by this paper
• Microfluidic Organ-on-a-Chip Devices for Liver Disease Modeling In Vitro

  2022cited by this paper
• Heterogeneity of non-alcoholic fatty liver disease: Implications for clinical practice and research activity

  2021cited by this paper
• Epigenetic Regulation of Kupffer Cell Function in Health and Disease

  2021cited by this paper
• Liver–Heart on chip models for drug safety

  2021cited by this paper
• Liver-on-a-chip platform to study anticancer effect of statin and its metabolites

  2021cited by this paper
• Liver-lobule-mimicking patterning via dielectrophoresis and hydrogel photopolymerization

  2021cited by this paper
• Insights into Macrophage/Monocyte-Endothelial Cell Crosstalk in the Liver: A Role for Trem-2

  2021cited by this paper
• Modelling human liver fibrosis in the context of non-alcoholic steatohepatitis using a microphysiological system

  2021cited by this paper
• On-Chip Construction of Liver Lobules with Self-Assembled Perfusable Hepatic Sinusoid Networks.

  2021cited by this paper
• Development of a Hybrid Polymer-Based Microfluidic Platform for Culturing Hepatocytes towards Liver-on-a-Chip Applications

  2021cited by this paper
• Experimental liver models: From cell culture techniques to microfluidic organs‐on‐chip

  2021cited by this paper
• Investigation of steatosis profiles induced by pesticides using liver organ-on-chip model and omics analysis.

  2021cited by this paper
• Mechanism of cholangiocellular damage and repair during cholestasis.

  2021cited by this paper
• A 3D bio-printed spheroids based perfusion in vitro liver on chip for drug toxicity assays

  2021cited by this paper
• Liver Disease: Induction, Progression, Immunological Mechanisms, and Therapeutic Interventions

  2021cited by this paper

• Investigation of Permeability and Flow Dynamics in Liver on a Chip: An Integrated Experimental and Computational Study

  2026cites this paper