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1 Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA
2 Department of Mathematical Sciences, Worcester Polytechnic Institute, Worcester, MA, USA
* To whom correspondence should be addressed. E-mail: sliu{at}northwestern.edu.
Smooth muscle cells (SMCs) are organized in various patterns in blood vessels. While straight blood vessels mainly contain circumferentially aligned SMCs, curved blood vessels comprise axially aligned SMCs in regions with vortex blood flow. The vortex flow-dependent feature of SMC alignment suggests a role for nonuniform fluid shear stress in regulating the pattern formation of SMCs. Here we demonstrate that, in experimental models with vascular polymer implants designed for the observation of neointima formation and SMC migration under defined fluid shear stress, nonuniform shear stress possibly plays a role in regulating the direction of SMC migration and alignment in the neointima of the vascular implant. It was found that fluid shear stress inhibited cell growth, and the presence of nonuniform shear stress influenced the distribution of total cell density and induced the formation of cell density gradients, which in turn directed SMC migration and alignment. In contrast, uniform fluid shear stress in a control model influenced neither the distribution of total cell density, nor the direction of SMC migration and alignment. In both uniform and nonuniform shear model, the gradient of total cell density was consistent with the alignment of SMCs. These observations suggest that nonuniform shear stress may regulate the pattern formation of SMCs, possibly via mediating the gradient of total cell density in the neointima of vascular polymer implants.
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