Investigation into the effect of the aspect ratio of cylindrical surface microstructure on von Willebrand factor damage

Abstract

Hemorrhagic episodes in patients carrying mechanical circulatory support represent a severe clinical complication. These bleeding episodes may originate from a reduced functionality of von Willebrand factor (VWF), a multimer protein pertinent to form a hemostatic plug. The reduced functionality is due to increased loss of high molecular weight von Willebrand factor multimers (HMWM-VWF), a phenomenon that is facilitated by device-induced increases in shear stress to which VWF is exposed. However, in addition to the mechanics factors, VWF damage may also be affected by interface factors, including the properties of bulk material and the surface characteristics. In this study, the effect of cylindrical surface microstructure topography on VWF damage was investigated. In the 1 to 9 range, the high aspect ratio surface features were constructed on the polycarbonate (PC) films. The topographic surfaces were fabricated by 3D printing casting on a template. A roller pump circulation platform was built to conduct in vitro experiments. VWF antigen (VWF-Ag) and VWF ristocetin cofactor activity (VWF-Rico) on these topographic surfaces were quantified by enzyme-linked immunosorbent assay (ELISA), the loss of HMWM-VWF was quantified by immunoblotting. The lower loss of HMWM-VWF was observed on surfaces with high aspect ratio compared to the pristine PC templates and surfaces with low aspect ratio, while VWF-Ag was nearly unchanged. The topographical parameters found to significantly reduce the loss of HMWM-VWF were high aspect ratio structures of more than 5. The results signify that topographical manipulation of surfaces is a feasible approach for reducing the loss of HMWM-VWF.