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Combined In Silico and In Vitro Approach Predicts Low Wall Shear Stress Regions in a Hemofilter that Correlate with Thrombus Formation In Vivo

Buck, Amanda K. W.*†; Groszek, Joseph J.; Colvin, Daniel C.*; Keller, Sara B.§; Kensinger, Clark; Forbes, Rachel; Karp, Seth; Williams, Phillip; Roy, Shuvo; Fissell, William H.

doi: 10.1097/MAT.0000000000000649
Biomedical Engineering

A major challenge in developing blood-contacting medical devices is mitigating thrombogenicity of an intravascular device. Thrombi may interfere with device function or embolize from the device to occlude distant vascular beds with catastrophic consequences. Chemical interactions between plasma proteins and bioengineered surface occur at the nanometer scale; however, continuum models of blood predict local shear stresses that lead to platelet activation or aggregation and thrombosis. Here, an iterative approach to blood flow path design incorporating in silico, in vitro, and in vivo experiments predicted the occurrence and location of thrombi in an implantable hemofilter. Low wall shear stress (WSS) regions identified by computational fluid dynamics (CFD) predicted clot formation in vivo. Revised designs based on CFD demonstrated superior performance, illustrating the importance of a multipronged approach for a successful design process.

From the *Department of Radiology and Radiological Sciences, Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center (VUMC), Nashville, Tennessee; Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee; Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center (VUMC), Nashville, Tennessee; §Department of Bioengineering, University of Washington, Seattle, Washington; Department of Surgery, Vanderbilt University Medical Center (VUMC), Nashville, Tennessee; and Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California.

Submitted for consideration February 2017; accepted for publication in revised form July 2017.

This work was supported by grants from the National Institutes of Health (1R01EB014315 and 1U01EB021214), as well as a generous gift from the Wildwood Foundation.

Disclosure: S. Roy and W. H. Fissell have ownership in Silicon Kidney. The other authors have no conflicts of interest to report.

Correspondence: William H. Fissell, Division of Nephrology and Hypertension, Vanderbilt University Medical Center (VUMC), 1161 21st Ave South, MCN S-3223, Nashville, TN 37232. Email:

Copyright © 2018 by the American Society for Artificial Internal Organs