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Am J Physiol Heart Circ Physiol 284: H1771-H1777, 2003. First published January 16, 2003; doi:10.1152/ajpheart.01008.2002
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Vol. 284, Issue 5, H1771-H1777, May 2003

Fibroblast alignment under interstitial fluid flow using a novel 3-D tissue culture model

Chee Ping Ng1 and Melody A. Swartz1,2

1 Departments of Chemical Engineering and 2 Biomedical Engineering, Northwestern University, Evanston, Illinois 60208

Interstitial flow is an important component of the microcirculation and interstitial environment, yet its effects on cell organization and tissue architecture are poorly understood, in part due to the lack of in vitro models. To examine the effects of interstitial flow on cell morphology and matrix remodeling, we developed a tissue culture model that physically supports soft tissue cultures and allows microscopic visualization of cells within the three-dimensional matrix. In addition, pressure-flow relationships can be continuously monitored to evaluate the bulk hydraulic resistance as an indicator of changes in the overall matrix integrity. We observed that cells such as human dermal fibroblasts aligned perpendicular to the direction of interstitial flow. In contrast, fibroblasts in static three-dimensional controls remained randomly oriented, whereas cells subjected to fluid shear as a two-dimensional monolayer regressed. Also, the dynamic measurements of hydraulic conductivity suggest reorganization toward a steady state. These primary findings help establish the importance of interstitial flow on the biology of tissue organization and interstitial fluid balance.

cell culture; shear stress; mechanical stress; hydraulic conductivity


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