Utility of microfluidic devices to study the platelet-endothelium interface

Abstract

The integration of biomaterials and understanding of vascular biology has led to the development of perfusable endothelialized flow models, which have been used as valuable tools to study the platelet-endothelium interface under shear. In these models, the parameters of geometry, compliance, biorheology, and cellular complexity are varied to recapitulate the physical biology of platelet recruitment and activation under physiologically relevant conditions of blood flow. In this review, we summarize the mechanistic insights learned from perfusable microvessel models and discuss the potential utility as well as challenges of endothelialized microfluidic devices to study platelet function in the bloodstream in vitro.

Keywords: Endothelial cell; VWF; shear; vessel barrier.

Figure 1. The platelet-endothelium interface

Under laminar flow (depicted with arrows on left), healthy endothelial cells prevent platelet adhesion and aggregation by secreting soluble nitric oxide (NO) and prostacyclin (PGI₂). The surface of the endothelium is covered by an anti-adhesive layer of glycocalyx and expresses endonucleases (CD39), which hydrolyzes adenosine diphosphate (ADP), and thrombomodulin (TM), which promotes reduction of thrombin and an increase in antithrombotic activated protein C (APC), all of which serve to maintain platelets in their quiescent state. Upon vessel injury, platelets are rapidly recruited to subendothelial extracellular matrix (ECM) proteins via platelet glycoprotein (GP) Ib binding to the adhesive protein von Willebrand factor (VWF). Platelets are activated downstream of the collagen receptor GPVI leading to glycoprotein IIb/IIIa (GPIIb/IIIa)-dependent aggregate formation to prevent blood loss. Activated platelets release adenosine diphosphate (ADP) and thromboxane (TXA₂) and provide a surface for thrombin generation, all of which feedback to promote secondary recruitment and activation of platelets from the bloodstream to form a hemostatic plug.