Modeling Transport and Biomechanics of Pulmonary Capillary Networks in Health and Disease

Abstract The pulmonary capillary network (PCN) is a highly complex and dynamic structure essential for gas exchange and systemic homeostasis. Beyond its primary role in oxygen transport, the PCN also mediates a range of transport processes relevant to both health and disease. Scientific interest in PCN has evolved considerably over time, from early efforts characterizing its anatomy and architecture to modern investigations of its in situ microcirculatory dynamics using advanced imaging technologies. More recently, research has shifted toward developing biomimetic models—such as in vitro microfluidic systems and tissue-engineered constructs—that replicate the PCN's intricate structure and cellular function. These platforms now play a crucial role in disease modeling, drug delivery research, and the study of pulmonary microvascular biology under both physiological and pathological conditions. In this review, we first outline the anatomical and physiological characteristics of the PCN and discuss its roles in homeostasis and disease. We then examine classical biomechanical models of blood flow in the PCN, followed by an overview of recent advances in in vitro modeling approaches, with an emphasis on microfluidic platforms. Finally, we highlight emerging next-generation models designed to better replicate PCN complexity and discuss how they can accelerate the development of new therapeutic strategies.