Reconstituting organ-level lung functions on a chip.
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.
Huh
Dongeun
D
Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
Matthews
Benjamin D
BD
Mammoto
Akiko
A
Montoya-Zavala
Martín
M
Hsin
Hong Yuan
HY
Ingber
Donald E
DE
D000388:Air; D056809:Alveolar Epithelial Cells / Q000502:physiology*; D000818:Animals; D040761:Biomimetic Materials; D015824:Blood-Air Barrier; D002196:Capillaries / Q000502:physiology*; D002199:Capillary Permeability; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D008168:Lung / Q000098:blood supply / Q000502:physiology; D051379:Mice; D046210:Microfluidic Analytical Techniques; D055616:Microtechnology; D053758:Nanoparticles / Q000633:toxicity; D020556:Neutrophil Infiltration; D018384:Oxidative Stress; D011650:Pulmonary Alveoli / Q000098:blood supply* / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D012119:Respiration; D012822:Silicon Dioxide / Q000633:toxicity; D013314:Stress, Mechanical
D012822:Silicon Dioxide