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

Autor: Sakurai Y; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 345 Ferst Drive, Atlanta, GA, 30332, USA.; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Hardy ET; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 345 Ferst Drive, Atlanta, GA, 30332, USA.; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Ahn B; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 345 Ferst Drive, Atlanta, GA, 30332, USA.; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Tran R; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 345 Ferst Drive, Atlanta, GA, 30332, USA.; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Fay ME; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 345 Ferst Drive, Atlanta, GA, 30332, USA.; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Ciciliano JC; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive, Atlanta, GA, 30332, USA., Mannino RG; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 345 Ferst Drive, Atlanta, GA, 30332, USA.; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Myers DR; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 345 Ferst Drive, Atlanta, GA, 30332, USA.; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Qiu Y; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 345 Ferst Drive, Atlanta, GA, 30332, USA.; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Carden MA; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Baldwin WH; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Meeks SL; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA., Gilbert GE; Medicine Depts of VA Boston Healthcare System and Harvard Medical School, 150 S Huntington Ave, Boston, Massachusetts, 02130, USA., Jobe SM; Blood Center of Wisconsin, 8733W Watertown Plank Road, Wauwatosa, WI, 53226, USA. Shawn.Jobe@BCW.edu., Lam WA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 345 Ferst Drive, Atlanta, GA, 30332, USA. wilbur.lam@emory.edu.; Department of Pediatrics, Divisoin of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, Atlanta, GA, 30322, USA. wilbur.lam@emory.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2018 Feb 06; Vol. 9 (1), pp. 509. Date of Electronic Publication: 2018 Feb 06.
DOI: 10.1038/s41467-018-02990-x
Abstrakt: 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.
Databáze: MEDLINE