Next-Generation Respiratory Models: Bridging the Gap Between Biology and Bioengineering

The development of in vitro respiratory model systems has advanced physiological understanding and clinical strategies by creating multi-dimensional platforms that replicate in vivo-like microenvironments. These systems bridge the gap between conventional models and human biology, providing insights into respiratory physiology and disease mechanisms. Recent innovations integrate advanced technologies to meet the growing demand for physiologically relevant and disease-specific platforms. In this review, we highlight the recent advances in in vitro respiratory model systems that recapitulate key aspects of human respiratory anatomy and function to facilitate disease modeling. We focus on 2.5D on-chip systems, 3D biological models, and bioprinting structures, each providing distinct advantages for constructing physiologically relevant models. We outline the engineering principles underlying these techniques and evaluate their ability to mimic structural and functional features of the respiratory system, supported by representative examples and clinical relevance. Finally, we discuss current challenges and future directions, highlighting the potential of advanced in vitro respiratory models to accelerate translational research and therapeutic development.