Our goal was to develop a model of the microvasculature that would allow us to quantify changes in the rheology of sickle blood as it traverses the varying vessel sizes and oxygen tensions in the microcirculation. We designed and implemented a microfluidic model of the microcirculation that comprises a branching microvascular network and physiologic oxygen gradients. We used computational modeling to determine the parameters necessary to generate stable, linear gradients in our devices. Sickle blood from six unique patients was perfused through the microvascular network and subjected to varying oxygen gradients while we observed and quantified blood flow. We found that all sickle blood samples fully occluded the microvascular network when deoxygenated, and we observed that sickle blood could cause vaso-occlusions under physiologic oxygen gradients during the microvascular transit time. The number of occlusions observed under five unique oxygen gradients varied among the patient samples, but we generally observed that the number of occlusions decreased with increasing inlet oxygen tension. The model system we have developed is a valuable tool to address fundamental questions about where in the circulation sickle-cell vaso-occlusions are most likely to occur and to test new therapies.
Bibliographical noteFunding Information:
This work was supported by the National Heart, Lung, and Blood Institute (NHLBI) under grants R21HL130818 and R56HL132906. J.M.H. was also supported by NHLBI grant HL114476, and a National Institutes of Health (NIH) Director's New Innovator Award (DP2DK098087). D.K.W. was also supported by the American Heart Association under grant 13SDG6450000. X.L. was also supported under predoctoral fellowship 16PRE31020025 from the American Heart Association For support with blood sample collection, identification, testing, and transport, the authors would like to thank Dr. Yvonne Data at the University of Minnesota Medical Center and thank the University of Minnesota Advanced Research and Diagnostic Laboratory as well as Judith Oakley, Kerry Breen, Sofia Shaikh, John Yablonski, and other members of the MGH Clinical Laboratories and the MGH Clinical Research Program. Video processing for tracked blood velocities was performed on the Harvard Medical School Orchestra Computing Cluster. The authors also thank the Minnesota Nanofabrication Center for device fabrication support and the Minnesota Supercomputing Institute for simulation support.
© 2017 John Wiley & Sons Ltd
- oxygen gradient
- sickle-cell disease