128 Chapter 6 ABSTRACT In vitro models for investigating mechanisms underlying repair and regeneration in lung disease have advanced greatly in the last decades. Of these models, 3-dimensional (3D) models are particularly interesting owing to their enhanced resemblance of the physiological conditions in vivo. 3D in vitro models can be created using natural or synthetic biomaterials; where utilizing the extracellular matrix (ECM) from the lung itself or ECM-derived biomaterials have improved our understanding of lung disease and repair mechanisms. Homeostasis of lung ECM is critically important for the function of the lungs for gas exchange, and disruption of the ECM occurs in most chronic lung diseases. Reflecting the complexity of the architecture of lung tissue, several different types of in vitro models based on ECM have been developed. Materials derived from collagen, gelatin, hyaluronic acid and their derivatives are among the most used single ECM protein-based models. Although these models lack the 3D architecture and organization of the native ECM, they facilitate the collection of extensive information via mimicking the lung microenvironment in health and disease. Decellularized lung matrices have been used as scaffolds for in vitro models enabling the preservation of native architecture and composition within the ECM. However, reintroducing and imaging to localize cells poses some novel challenges when working within these 3D models. Hydrogels prepared using these decellularized lung matrices are emerging as a new opportunity, bringing the native lung ECM composition and the ability to control the model shape together. In this chapter, we discuss the ECM-based 3D in vitro models for lung disease, repair and regeneration. First, we briefly outline the lung ECM and the changes associated with chronic lung diseases. Then we summarize the progress and the state-ofthe-art research performed using these models, discussing the advantages and challenges related to these models and summarizing the properties of an ideal 3D model.
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