Dongeun Huh
*,
, Hideki
Fujioka
*, Yi-Chung Tung
*,
Nobuyuki Futai
*, Robert Paine, III
,
, James B.
Grotberg
*, and Shuichi
Takayama
*,¶,||
Departments of *Biomedical Engineering and ¶Macromolecular Science
and Engineering, University of Michigan, Ann Arbor, MI 48109-2099; and Division of Pulmonary and
Critical Care Medicine, Department of Internal Medicine, University of Michigan,
Ann Arbor, MI 48105
Edited by Howard A. Stone, Harvard University, Cambridge, MA, and accepted by
the Editorial Board September 10, 2007 (received for review December 7, 2006)
Abstract
We describe a microfabricated airway system integrated with
computerized air-liquid two-phase microfluidics that enables
on-chip engineering of human airway epithelia and precise
reproduction of physiologic or pathologic liquid plug flows found in
the respiratory system. Using this device, we demonstrate
cellular-level lung injury under flow conditions that cause symptoms
characteristic of a wide range of pulmonary diseases. Specifically,
propagation and rupture of liquid plugs that simulate
surfactant-deficient reopening of closed airways lead to significant
injury of small airway epithelial cells by generating deleterious
fluid mechanical stresses. We also show that the explosive pressure
waves produced by plug rupture enable detection of the mechanical
cellular injury as crackling sounds.
airway reopening | small airway epithelial cells | mechanical
forces | microfluidic cell culture
Footnotes
Author contributions: D.H., R.P., J.B.G., and
S.T. designed research; D.H. performed research; H.F., Y.-C.T., N.F.,
and J.B.G. contributed new reagents/analytic tools; D.H., H.F.,
Y.-C.T., J.B.G., and S.T. analyzed data; and D.H. and S.T. wrote
the paper.
Present address: Vascular Biology Program, Departments of
Pathology and Surgery, Harvard Medical School and Children''s
Hospital, Boston, MA 02115.
Present address: Department of Internal Medicine and
Division of Pulmonary and Critical Care Medicine, University of
Utah School of Medicine, Salt Lake City, UT 84132.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. H.A.S.
is a guest editor invited by the Editorial Board.
||To whom correspondence should be
addressed at: Department of Biomedical Engineering, University of Michigan, 2200
Bonisteel Boulevard, 2115 Gerstacker, Ann Arbor, MI 48109-2099.
박성희 (University of Pennsylvania)
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