Abstract
Determining the mechanistic causes of lung diseases, developing new treatments thereof, and assessing toxicity whether from chemical exposures or engineered nanomaterials would benefit significantly from a preclinical human lung alveolar interstitium model of physiological relevance. The existing preclinical models have limitations because they fail to replicate the key anatomical and physiological characteristics of human alveoli. Thus, a human lung alveolar interstitium chip was developed to imitate key alveolar microenvironmental factors including an electrospun nanofibrous membrane as the analogue of the basement membrane for co-culture of epithelial cells with fibroblasts embedded in 3D collagenous gels, physiologically relevant interstitial matrix stiffness, interstitial fluid flow, and 3D breathing-like mechanical stretch. The biomimetic chip substantially improved the epithelial barrier function compared to transwell models. Moreover, the chip having a gel made of a collagen I-fibrin blend as the interstitial matrix sustained the interstitium integrity and further enhanced the epithelial barrier, resulting in a longevity that extended beyond eight weeks. The assessment of multiwalled carbon nanotube toxicity on the chip was in line with the animal study.
Original language | English (US) |
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Pages (from-to) | 36888-36898 |
Number of pages | 11 |
Journal | ACS Applied Materials and Interfaces |
Volume | 15 |
Issue number | 30 |
DOIs | |
State | Published - Aug 2 2023 |
Keywords
- alveolar interstitium
- lung chip
- matrix stiffness
- mechanical stretch
- nanofibrous membrane
- permeability
ASJC Scopus subject areas
- General Materials Science