Scalability and translational potential of advanced in vitro airway and lung models for personalised medicine and drug screening

Abstract

Advanced in vitro respiratory models, including air-liquid interface (ALI) cultures, airway and lung organoids and airway- and lung-on-a-chip platforms, have gained considerable attention as physiologically relevant systems for studying respiratory diseases, evaluating drug responses, and personalised medicine. While these models offer clear biological advantages over traditional cell cultures and animal studies, their successful translation into widespread research and clinical use also depends on their scalability, experimental capacity, practicality and cost-effectiveness. To date, these aspects have received less systematic evaluation than biological performance, limiting informed decisions regarding their implementation in drug development and translational pipelines. Here, the scalability of these three advanced respiratory models is critically assessed to determine and compare their translational potential and applicability for personalised medicine and drug screening. Key aspects, including experimental capacity, costs, practicality and (technical) complexity are examined in detail. Besides, recent advances and major barriers for scaling up these models are highlighted. Finally, emerging strategies to improve scalability and standardisation are discussed, alongside prospects for their broader translational adoption.