3D In Vitro Models: Novel Insights into Idiopathic Pulmonary Fibrosis Pathophysiology and Drug Screening

Idiopathic pulmonary fibrosis (IPF) is a progressive and often lethal interstitial lung disease of unknown aetiology. IPF is characterised by myofibroblast activation, tissue stiffening, and alveolar epithelium injury. As current IPF treatments fail to halt disease progression or induce regeneration, there is a pressing need for the development of novel therapeutic targets. In this regard, tri-dimensional (3D) models have rapidly emerged as powerful platforms for disease modelling, drug screening and discovery. In this review, we will touch on how 3D in vitro models such as hydrogels, precision-cut lung slices, and, more recently, lung organoids and lung-on-chip devices have been generated and/or modified to reveal distinct cellular and molecular signalling pathways activated during fibrotic processes. Markedly, we will address how these platforms could provide a better understanding of fibrosis pathophysiology and uncover effective treatment strategies for IPF patients.