Network Trauma Research Series: Modeling Trauma Complexity - In Vitro Models to Study Traumatic Lung Damage

Polytrauma, defined as severe injury to multiple body regions, frequently affects the head and thorax and induces a systemic immune response that can favor secondary infections such as pneumonia. In particular, thoracic trauma substantially increases the risk of post-traumatic pneumonia, as direct lung injury, impaired respiratory function, and the frequent need for mechanical ventilation predispose patients to pulmonary infections, thereby contributing to adverse clinical outcomes. To improve translational understanding of these interactions, complex in vitro models have been developed to experimentally dissect the biological mechanisms underlying injuries of the lung. This review provides a comprehensive overview of current in vitro lung models and their suitability to analyze trauma induced lung damage and following infection. Key methodological variables are the selection of appropriate cell lines, the modeling of air - liquid interface or barrier function and the simulation of the trauma. Importantly, experimental approaches should clearly distinguish between inflammatory stimulation and mechanical injury, as these represent distinct pathophysiological processes. Collectively, the models discussed herein highlight the importance of standardized and physiologically relevant in vitro trauma models for advancing mechanistic insights and facilitating the development of targeted therapeutic strategies.