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

• Type of Material: Article
• Authors: Yumiko Sakurai, Georgia Institute of Technology; Elaissa T. Hardy, Georgia Institute of Technology; Byungwook Ahn, Georgia Institute of Technology; Reginald Tran, Georgia Institute of Technology; Meredith E. Fay, Georgia Institute of Technology; Jordan C. Ciciliano, Georgia Institute of Technology; Robert G. Mannino, Georgia Institute of Technology; David R Myers, Emory University; Yongzhi Qiu, Georgia Institute of Technology; Marcus A. Carden, Emory University; W. Hunter Baldwin, Emory University; Shannon L. Meeks, Emory University; Gary E. Gilbert, Virginia Boston Healthcare System; Shawn M. Jobe, Blood Center of Wisconsin; Wilbur Lam, Emory University
• Language: English
• Date: 2018-02-06
• Publisher: Nature Publishing Group: Nature Communications
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-018-02990-x
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 9
• Issue: 1
• Start Page: 509
• End Page: 509
• Grant/Funding Information: Financial support was provided by NIH R01 (HL121264, HL130918), NIH U54 (HL112309), and NSF CAREER (1150235) to W.A.L.; Also, this work was performed in part at the Georgia Tech Institute for Electronics and Nanotechnology, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by NSF ECCS (1542174).
• Keywords: IN-VIVO; Multidisciplinary Sciences; Science & Technology - Other Topics; ANTIBODIES; PLATELETS; PHOSPHATIDYLSERINE; THROMBOSIS; PROCOAGULANT; MICROFLUIDIC TECHNOLOGY; GENERATION; Science & Technology; VON-WILLEBRAND-FACTOR; COAGULATION
• Research Categories: Health Sciences, Medicine and Surgery

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.