Organs-on-Chips for Disease Modeling and Drug Development: Engineering, Validation and Medical Translation

Abstract

Introduction: about nine in ten drug candidates that enter clinical development fail, partly because preclinical models, including animal models, predict human responses poorly. Organs-on-chips (OoCs), microfluidic devices lined with living human cells under fluid flow, have emerged as engineered alternatives that reproduce organ-level physiology. Objective: to critically describe the engineering principles of OoCs, the evidence on their predictive value in toxicology and pharmacology, their use in disease modeling and personalized medicine, and the regulatory and technical barriers to their adoption. Development: a human Liver-Chip evaluated with a blinded set of 27 drugs reached a reported sensitivity of 87% and specificity of 100% for drug-induced liver injury, and an airway chip identified antiviral candidates that cell lines under static conditions missed. Patient-derived organoids integrated into chips are being explored for personalized drug screening. Regulatory frameworks have begun to accept non-animal methods, but unresolved issues include small-molecule absorption by device materials, limited throughput, scarce standardization and the lack of prospective clinical validation. Conclusions: OoCs are a promising complement to conventional preclinical models rather than a proven replacement; their clinical value will depend on independent validation, standardization and clearly defined contexts of use.