Reconstituting Organ-Level Lung Functions on a Chip

TLDR

The study presents a biomimetic microsystem that recreates the human lung’s alveolar‑capillary interface. The device is a bioinspired microdevice that reproduces organ‑level responses to bacteria and inflammatory cytokines introduced into the alveolar space. Nanotoxicology studies revealed that cyclic mechanical strain amplifies silica nanoparticle toxicity and inflammation, increases epithelial and endothelial uptake, and promotes transport into the microvascular channel, with similar effects seen in whole mouse lungs, suggesting that mechanically active organ‑on‑a‑chip devices can expand drug screening and toxicology applications.

Abstract

Here, we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This bioinspired microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space. In nanotoxicology studies, this lung mimic revealed that cyclic mechanical strain accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticulates and stimulates their transport into the underlying microvascular channel. Similar effects of physiological breathing on nanoparticle absorption are observed in whole mouse lung. Mechanically active "organ-on-a-chip" microdevices that reconstitute tissue-tissue interfaces critical to organ function may therefore expand the capabilities of cell culture models and provide low-cost alternatives to animal and clinical studies for drug screening and toxicology applications.