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February 8, 2018

Model Wound System Created that Self Heals

  • Watch as blood cells stream through a "wound" and a clot forms. The red-stained cells are actually white blood cells. A green extracellular glue can be seen at the top of the wound; this is fibrin, which holds the clot together. [Yumiko Sakurai/Emory/Georgia Tech]
  • Scientists say they have developed a miniature self-sealing model system for studying bleeding and the clotting of wounds. They view the device as a drug discovery platform and potential diagnostic tool that is described in Nature Communications (“A Microengineered Vascularized Bleeding Model That Integrates the Principal Components of Hemostasis”).

    “...here we develop a comprehensive in vitro mechanical injury bleeding model comprising an ‘endothialized’ 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,” write the investigators.

    “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.”

    According to Wilbur Lam, M.D., Ph.D., blood clotting involves the damaged blood vessel, platelets, blood clotting proteins that form a net-like mesh, and the flow of the blood itself.

    "Current methods to study blood clotting require isolation of each of these components, which prevents us from seeing the big picture of what's going with the patient's blood clotting system," says Dr. Lam, assistant professor in the department of pediatrics at Emory University School of Medicine and in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

    The model is the result of a collaboration between Lam's group at Emory and Georgia Tech and Shawn Jobe, M.D., Ph.D. at the Blood Center of Wisconsin. The co-first authors of the paper are research specialist Yumiko Sakurai, instructor Elaissa Hardy, Ph.D., and senior engineer Byungwook Ahn, Ph.D., now at LG Electronics.

    The system reportedly is the first to reproduce all the aspects of blood vessel injury seen in the microvasculature: blood loss due to trauma, clot formation by whole blood, and repair of the blood vessel lining. Previous models might only simulate clot formation, notes Dr. Lam, adding that the model does not include smooth muscle and does not reproduce aspects of larger blood vessels, however.

    The system consists of a layer of human endothelial cells, which line blood vessels, cultured on top of a pneumatic valve. The "wound" is created by activating a pneumatic valve, opening what Dr. Lam calls a trap door. Donated human blood flows through the wound, which is about 130 μm across.

    In real time, it takes about 8 minutes for blood flow into the wound to stop. Without the endothelial cells, the blood flow does not stop.

    The system responds to manipulation by drugs and other alterations that reproduce clotting disorders. Blood from hemophilia A patients forms abnormal clots and shows extended bleeding time in the model.

    In the Nature Communications paper, the authors also describe insights into how the drug eptifibatide affects the interactions of platelets and other cells in the 3D space of a wound.

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