Table 2.

Recent lung chip systems for modeling pathophysiologic states, lung injury, fibrotic response, and therapeutic testing.

Modeling Approach	Cellular Composition	Key Outcome	References
Normal Physiologic State	Human alveolar epithelial and pulmonary endothelial cells	Inflammatory, immune, and stress reactions to pollutants.	[64]
	Airway epithelial cells, lung fibroblast, and endothelial cells	Multi-layered, co-cultured replicating cellular composition of lung.	[65]
	Type I and II alveolar epithelial cells, endothelial cells	Medium-throughput physiologic three-dimensional stretching system	[66]
	Alveolar epithelial and endothelial cells	collagen-elastin membrane replicating geometric and biophysical characteristics of ECM	[62]
	Alveolar epithelial cells and fibroblasts	Enhanced nano spun pseudo-interstitium, improving epithelial barrier function and longevity.	[67]
Alveolar Injury	Human type II A549	Exposure to gastric contents induced cellular injury.	[68]
	Human pulmonary alveolar epithelial and umbilical vascular endothelial cells	Nanoparticles cause dose-dependent toxicity to lung cells	[69]
	Human alveolar epithelial cells, pulmonary vascular endothelial cells, and human acute leukemia monocytic cell lines (THP-1)	Air pollutants disrupt alveolar-capillary interface, induce inflammation, and trigger immune cell recruitment.	[70]
	Immortalized human alveolar epithelial cell lines (iAECs), primary human lung microvascular endothelial cells, and peripheral blood mononuclear cells (PBMCs).	Bacterial endotoxin exposure causing alveolar barrier disruption and inflammation.	[71]
	Human primary alveolar epithelial cells and human lung microvascular endothelial cells (HMVEC-L)	Radiation induced lung injury. Therapeutic response to lovastatin and prednisolone.	[72]
Induction of Fibrosis	Pulmonary Fibroblast	Simulate fibrotic events, predicts antifibrotic effects of pirfenidone and nintedanib	[73]
	Primary human lung microvascular endothelial cells iAECs, and PBMCs	TGFβ1 induced epithelial to mesenchymal transition.	[71]
	Human-induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) and primary human lung fibroblast.	Stromal-endothelial interactions modulate changes in vessel density, expression levels, and tissue stiffness.	[74]
Therapeutic Testing and Drug Delivery	Primary human lung fibroblasts	Antifibrotic drug efficacy.	[75]
	Primary cell-derived immortalized alveolar epithelial cells (AXiAECs), macrophages (THP-1), and endothelial (HLMVEC) cells	Aerosol delivery system and inhaled steroid efficacy.	[76]