Organ-on-a-Chip Technology in Otorhinolaryngology: Design Strategies and Applications in Mucosal Tissues and Head and Neck Cancer

The complex mucosal microenvironment of the upper aerodigestive tract influences otorhinolaryngologic diseases. Therefore, establishing preclinical models that recapitulate the structural and functional characteristics of otorhinolaryngologic tissues is important for understanding disease pathophysiology and evaluating therapeutic responses. Recently, organ-on-a-chip (OoC) has emerged as a promising in vitro approach to address limitations of conventional models. OoC can reproduce key tissue-level features under controlled microenvironmental conditions by integrating relevant cell or tissue sources, spatial organization, dynamic culture conditions, and multicellular interactions. In this review, we focus on representative OoC applications in oral mucosa and gingiva, nasal mucosa and airway, and head and neck cancer (HNC). We discuss how OoC design strategies are tailored to the intended biological or preclinical application and summarize the current applications, translational challenges, and future directions of these models. Continued advances in patient-relevant model development, reproducibility, standardization, and validation against in vivo and clinical findings may further strengthen the role of OoC as a complementary preclinical platform in otorhinolaryngology.