Biomimetic Human Lung Alveolar Interstitium Chip with Extended Longevity

Area of Science:

• Biomedical Engineering
• Pulmonary Medicine
• Toxicology

Background:

• Current preclinical lung models lack the anatomical and physiological relevance of human alveoli.
• This limits understanding of lung diseases and toxicity assessments.
• There is a need for advanced models that replicate the human lung interstitium.

Purpose of the Study:

• To develop a human lung alveolar interstitium chip that replicates key microenvironmental factors.
• To enhance the physiological relevance of preclinical lung models.
• To provide a platform for studying lung diseases and assessing toxicity.

Main Methods:

• Developed a biomimetic chip with an electrospun nanofibrous membrane, mimicking the basement membrane.
• Co-cultured epithelial cells with fibroblasts in 3D collagenous gels.
• Incorporated interstitial fluid flow and breathing-like mechanical stretch.

Main Results:

• The chip demonstrated significantly improved epithelial barrier function compared to transwell models.
• A collagen I-fibrin blend matrix enhanced barrier function and model longevity beyond eight weeks.
• Milled carbon nanotube toxicity assessments on the chip aligned with animal study findings.

Conclusions:

• The developed human lung alveolar interstitium chip offers superior physiological relevance for preclinical lung research.
• This model enhances epithelial barrier function and provides a robust platform for toxicity testing.
• The chip represents a significant advancement for studying lung diseases and their mechanistic causes.