149 3D lung models – 3D extracellular matrix models provides improved mimicry due to its resemblance to the physiological conditions, as in vivo the cells reside in a 3D network of native ECM proteins. These 3D culture setups can be realized via various means, with one of the well-characterized methods using individual components isolated from ECM. Collagen, gelatin or hyaluronic acid and their derivatives have been extensively studied, and thanks to the advances in the field of biomaterials, they provide great versatility in their applications for modeling lung disease and regeneration. Tunable mechanical properties, pore size, and fiber diameter in these models allow researchers to investigate the connections between the mechanical microenvironment and the cells in lung disease. Decellularized lung ECM, on the other hand, provides the physiologic architecture of the lung tissue, as well as preserving the native composition of the ECM. Using native decellularized lung ECM to understand how disease progresses and the underlying mechanisms has provided valuable information, not only to understand how cells interact with the ECM, but also how the 3D architecture of the lung tissue microenvironment plays a role in such interactions. Recently, processing these matrices to create a hydrogel derived from lung ECM itself has been demonstrated. In addition to keeping the native ECM composition, the biomechanical properties of these hydrogels resembled the biomechanical properties of tissue as well. Using diseased or healthy lung ECMderived hydrogels alone or in combination with other materials to create advanced in vitro models will further improve our knowledge on lung diseases, repair and regeneration mechanisms. 6
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