TABLE I.

List for in vitro bionic lung-on-a-chip based on microfluidic chip technology.

Diseases mimicking		Cell types	Factors investigated	Features	Ref.
Lung injury	Mechanical cellular injury; ventilator-induced lung injury; acute respiratory distress syndrome; neonatal respiratory distress syndrome	Primary human small airway epithelial cells	Deleterious fluid mechanical stresses; air–liquid interface culture	Porous membrane sandwiched microchip; physiologic or pathologic liquid plug flows	Huh et al. (Ref. 41)
		A549; primary murine alveolar epithelial cells	Combined effects of fluid mechanical and solid mechanical stress	Porous membrane sandwiched microchip; surface tension forces	Douville et al. (Ref. 44)
		A549	Fluid mechanical stresses of liquid plug propagation in airways; Survanta surfactant	Porous membrane sandwiched microchip; the protective role of surfactants in liquid plugs	Tavana et al. (Ref. 48)
Lung inflammation	Asthmatic; chronic obstructive pulmonary disease (COPD); pulmonary edema; emphysema; pulmonary diseases caused by particle transport and deposition	Beas-2B; primary human fibrocytes	Eosinophil cationic protein (ECP); medium flow	Porous silicon membrane sandwiched microchip; fibrocyte extravasation	Punde et al. (Ref. 30)
		Human alveolar epithelial cells; endothelium cells, neutrophils	Mechanical stretching; air–liquid interface culture; cytokines (ICAM-1,TNF-a); bacterial, nanoparticles and interleukin-2	Porous membrane sandwiched microchip; alveolar-capillary barrier	Huh et al. (Ref. 36)
		Human alveolar epithelial cells; HUVECs	Nanoparticles (TiO2 and ZnO); cell coculture; blood vessel-tissue interface	Multichannel microfluidic chip; perfusion culture	Zhang et al. (Ref. 46)
		Calu-3; human bronchial smooth muscle cells	Rat-tail type I collagen and Matrigel; cell coculture	Multilayer PMMA chip	Humayun et al. (Ref. 47)
		A549	Particles; airflow and medium flow	PMMA chip; computational fluid dynamics simulation	Moghadas et al. (2018) (Ref. 49)
		Primary human airway epithelial cells; neutrophils	Interleukin-13; inflammatory cytokines; air–liquid interface culture	Porous membrane sandwiched microchip; secretion of the inflammatory cytokines	Benam et al. (2016) (Ref. 50)
		Primary human airway epithelial cells obtained from healthy donors or COPD patients	Cigarette smoke extract (CSE); cigarette smoke condensate (CSC)	Porous membrane sandwiched microchip; smoke-induced pathological microenvironment	Benam et al. (Ref. 51)
Pulmonary fibrosis	Pulmonary fibrosis	Primary human small airway epithelial cells	Antifibrotic drugs pirfenidone and nintedanib; TGF-β1; mechanical stretching and traction	Simulating the membranous morphology of the alveolar wall; PDMS micropillars	Asmani et al. (Ref. 55)
Lung cancer	Nonsmall cell lung cancer	A549; HFL1; HUVEC	Antitumor drug Gefitinib; IGF; cell coculture; 3D microenvironment	PLGA nanofiber membrane sandwiched microchip	Yang et al. (Ref. 57)