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.

In vitro comparative study of red blood cell and VWF damage on 3D printing biomaterials under different blood-contacting conditions

“…The surface microstructure of the material, such as roughness and hydrophilicity, may cause a different level of damage to the blood. 5,24 Therefore, the influence of material surface microstructure on blood damage should also be investigated in the future.…”

“…[1][2][3][4] However, it is often accompanied by the occurrence of hemocompatibility complications in clinical treatment, mainly including hemolysis, thrombosis, and gastrointestinal bleeding. 5,6 Hemolysis has been confirmed to be caused by the damage of red blood cells, thrombosis is mainly caused by platelet activation due to high shear stress, and the main trigger of gastrointestinal bleeding complication is the degradation of high molecular weight von Willebrand Factor (VWF). In addition to shear stress and exposure time, 7,8 which are considered to be two key mechanical factors contributing to blood damage, the blood-contacting materials in Mechanical Circulatory Support Devices (MCSDs) are equally likely to cause blood damage.…”

Constructing and evaluating the effect of micron-scale structures on von Willebrand factor damage

“…The details of collecting samples for VWF test were described in our previous research. 15 The perfusion tests were performed four groups under same condition using the same batch of plasma. The same procedure was repeated for each experiment.…”

“…In addition, we also found that VWF damage can be significantly reduced when the aspect ratio of material surface micro-structure (regular millimeter surface micro-structure) exceeds a certain range. 15 These studies indicated that the changes of interface factors caused by surface modification can also affect VWF damage besides mechanical factors. The development of micro-machining technology makes it possible to construct bionic micro-structures (regular surface micron-scale structures) on the material surface.…”