Reconstituting organ-level lung functions on a chip. Science 2010 Jun 25;328(5986):1662-8
Date
06/26/2010Pubmed ID
20576885Pubmed Central ID
PMC8335790DOI
10.1126/science.1188302Scopus ID
2-s2.0-77954038080 (requires institutional sign-in at Scopus site) 3007 CitationsAbstract
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.
Author List
Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DEAuthor
Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AirAlveolar Epithelial Cells
Animals
Biomimetic Materials
Blood-Air Barrier
Capillaries
Capillary Permeability
Cells, Cultured
Endothelial Cells
Escherichia coli
Humans
Immunity, Innate
Inflammation
Lung
Mice
Microfluidic Analytical Techniques
Microtechnology
Nanoparticles
Neutrophil Infiltration
Oxidative Stress
Pulmonary Alveoli
Respiration
Silicon Dioxide
Stress, Mechanical
