ORGANOIDS, ORGAN-ON-A-CHIP, AND 3D BIOPRINTING IN PRECLINICAL DRUG DEVELOPMENT AND DISEASE MODELING

Traditional preclinical models, including two-dimensional cell cultures and animal models, often fail to predict human drug efficacy and toxicity, contributing to high attrition rates in pharmaceutical development. Advanced in vitro models—organoids, organ-on-a-chip systems, and 3D bioprinted tissues—aim to better recapitulate human physiology and disease. Organoids are self-organizing three-dimensional structures derived from stem cells that mimic organ architecture and function. Organ-on-a-chip devices integrate living cells with microfluidic systems to replicate dynamic mechanical and biochemical environments. Three-dimensional bioprinting enables precise spatial deposition of cells and biomaterials to construct tissue-like structures. This review critically examines the current state and applications of these technologies in preclinical drug development and disease modeling, focusing on literature through early 2026. Organoids have been used to model genetic diseases, infectious diseases, and cancers, and to screen drug responses. Organ-on-a-chip systems have demonstrated utility in toxicology and pharmacokinetic studies, with multi-organ platforms emerging. 3D bioprinting offers scalability and architectural control, enabling fabrication of vascularized tissues. Challenges include standardization, reproducibility, scalability, and validation against human physiology. Future directions include integration of immune components, multi-organ connectivity, and regulatory acceptance as alternative methods. These platforms hold promise for reducing animal use and improving drug development efficiency.