Organoids-on-a-Chip: An Integrating New Technology for Drug Development

Organoids-on-a-chip integrate the three-dimensional structural fidelity of organoids with the dynamic microenvironmental control capabilities of microfluidic technology, providing a transformative preclinical research platform for drug development. This perspective catalogues organoids-on-a-chip systems encompassing liver, heart, tumor, neural, tissue barrier, and multi-organ integration platforms, and elaborates on their distinctive advantages in dynamically simulating the complete in vivo trajectory of drug absorption, distribution, metabolism, target engagement, and toxicological response. The mechanisms of this technology overcome the limitations associated with conventional static culture models, and interspecies disparities are elucidated. Furthermore, the applications of these systems across critical stages of drug development are summarized, including preclinical safety assessment, integrated pharmacokinetic/pharmacodynamic studies, personalized therapeutics, immunotherapy evaluation, and disease molecular mechanisms. Finally, we highlighted the main challenges facing this field and discussed future directions.