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Am J Physiol Heart Circ Physiol (January 16, 2003). doi:10.1152/ajpheart.01008.2002
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Submitted on November 21, 2002
Accepted on January 10, 2003

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

Chee Ping Ng1 and Melody A. Swartz2*

1 Department of Chemical Engineering, Northwestern University, Evanston, IL, USA
2 Department of Chemical Engineering, Northwestern University, Evanston, IL, USA; Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA

* To whom correspondence should be addressed. E-mail: m-swartz2{at}northwestern.edu.

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 have developed a tissue culture model that physically supports soft tissue cultures and allows microscopic visualization of cells within the 3-D matrix. In addition, pressure-flow relationships can be continuously monitored to evaluate the bulk hydraulic resistance as an indicator of changes in 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 3-D controls remained randomly oriented while cells subjected to fluid shear as a 2-D monolayer regressed. Also, the dynamic measurements of hydraulic conductivity suggest reorganization towards a steady state. These primary findings help establish the importance of interstitial flow on the biology of tissue organization and interstitial fluid balance.




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