A microengineered vascularized bleeding model that integrates the principal components of hemostasis

Yumiko Sakurai, Elaissa T. Hardy, Byungwook Ahn, Reginald Tran, Meredith E. Fay, Jordan C. Ciciliano, Robert G. Mannino, David R. Myers, Yongzhi Qiu, Marcus A. Carden, W. Hunter Baldwin, Shannon L. Meeks, Gary E. Gilbert, Shawn M. Jobe () and Wilbur A. Lam ()
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Yumiko Sakurai: Georgia Institute of Technology and Emory University
Elaissa T. Hardy: Georgia Institute of Technology and Emory University
Byungwook Ahn: Georgia Institute of Technology and Emory University
Reginald Tran: Georgia Institute of Technology and Emory University
Meredith E. Fay: Georgia Institute of Technology and Emory University
Jordan C. Ciciliano: Georgia Institute of Technology
Robert G. Mannino: Georgia Institute of Technology and Emory University
David R. Myers: Georgia Institute of Technology and Emory University
Yongzhi Qiu: Georgia Institute of Technology and Emory University
Marcus A. Carden: Aflac Cancer Center and Blood Disorders Center of Children’s Healthcare of Atlanta, Emory University School of Medicine
W. Hunter Baldwin: Aflac Cancer Center and Blood Disorders Center of Children’s Healthcare of Atlanta, Emory University School of Medicine
Shannon L. Meeks: Aflac Cancer Center and Blood Disorders Center of Children’s Healthcare of Atlanta, Emory University School of Medicine
Gary E. Gilbert: Medicine Depts of VA Boston Healthcare System and Harvard Medical School
Shawn M. Jobe: Blood Center of Wisconsin
Wilbur A. Lam: Georgia Institute of Technology and Emory University

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: Abstract Hemostasis encompasses an ensemble of interactions among platelets, coagulation factors, blood cells, endothelium, and hemodynamic forces, but current assays assess only isolated aspects of this complex process. Accordingly, here we develop a comprehensive in vitro mechanical injury bleeding model comprising an “endothelialized” microfluidic system coupled with a microengineered pneumatic valve that induces a vascular “injury”. With perfusion of whole blood, hemostatic plug formation is visualized and “in vitro bleeding time” is measured. We investigate the interaction of different components of hemostasis, gaining insight into several unresolved hematologic issues. Specifically, we visualize and quantitatively demonstrate: the effect of anti-platelet agent on clot contraction and hemostatic plug formation, that von Willebrand factor is essential for hemostasis at high shear, that hemophilia A blood confers unstable hemostatic plug formation and altered fibrin architecture, and the importance of endothelial phosphatidylserine in hemostasis. These results establish the versatility and clinical utility of our microfluidic bleeding model.

Date: 2018
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DOI: 10.1038/s41467-018-02990-x

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