Figure 7.

Overview of microfluidic device designs to mimic the lung. Pathological changes within the interstitial extracellular matrix (ECM) in the diseased lung. (A) Overview of the lung and sites of disease formation. (B) Healthy lung ECM is maintained by fibroblasts and represents a loose meshwork of protein anchored to the basal membrane of the epithelial cell layer. (C) In idiopathic pulmonary fibrosis (IPF), fibroblasts transdifferentiate to highly contractile myofibroblasts, depositing ECM and increasing its rigidity. (D) Chronic obstructive pulmonary disease (COPD) is characterized by the secretion of enzymes that degrade normal ECM, along with new ECM deposition by inflammatory cells. (E) In pulmonary arterial hypertension (PAH), remodeling of the ECM within the arterial wall is characterized by an increase in ECM proteins and hyperplasia of smooth muscle cells. (F) In asthma, the characteristic ECM changes take place beneath the bronchial epithelium and thickened basal membrane. (G) In cancer, tumors at primary and metastatic sides are surrounded by an extensive stiff stroma that contains highly crosslinked collagens, and specific proteins. (H) Legend depicting molecules and cell types. Reproduced with permission of the © ERS 2020: European Respiratory Journal 2017 50: 1601805; DOI: 10.1183/13993003.01805-2016.⁷⁶ (I-L) Existing microfluidic models are linked to their specific ECM patterns. (I) Microfluidic organotypic model of normal lung function⁹⁵, (J) COPD⁸², (K) asthma⁸⁶, (L) lung cancer⁷⁷. Reproduced from ref. 82 with permission from Springer Nature, copyright 2015. Reproduced from ref. 86 with permission from IOP Publishing, copyright 2018.