The Flow Dependent Adhesion of von Willebrand Factor (VWF)-A1 Functionalized Nanoparticles in an in Vitro Coronary Stenosis Model

Abstract

In arterial thrombosis, von Willebrand factor (VWF) bridges platelets to sites of vascular injury. The adhesive properties of VWF are controlled by its different domains, which may be engineered into ligands for targeting nanoparticles to vascular injuries. Here, we functionalized 200 nm polystyrene nanoparticles with the VWF-A1 domain and studied their spatial adhesion to collagen or collagen-VWF coated, real-sized coronary stenosis models under physiological flow. When VWF-A1 nano-particles (A1-NPs) were perfused through a 75% stenosis model coated with collagen-VWF, the particles preferentially adhered at the post stenotic region relative to the pre-stenosis region while much less adhesion was detected at the stenosis neck (~ 65-fold less). When infused through collagen-coated models or when the A1 coating density of nanoparticles was reduced by 100-fold, the enhanced adhesion at the post-stenotic site was abolished. In a 60% stenosis model, the adhesion of A1-NPs to collagen-VWF-coated models depended on the location examined within the stenosis. Altogether, our results indicate that VWF-A1 NPs exhibit a flow-structure dependent adhesion to VWF and illustrate the important role of studying cardiovascular nano-medicines in settings that closely model the size, geometry, and hemodynamics of pathological environments.

Computational and experimental investigation of particulate matter deposition in cerebral side aneurysms

“…We have previously reported a similar pattern in the study of arterial bifurcations and stenosed artery models, where we observed that particle impingement at the bifurcation and deposition in the internal carotid artery in vitro model prevented them from entering the carotid sinus circulation, resulting in a clearing in the sinus [39]. Similarly, in models of arterial stenosis, we observed that the re-attachment point of the post-stenotic circulation removed particles from the streamlines, leaving a large clearing between the narrowing and the re-attachment point [23].…”

“…This work provides a physical framework, supported by experimental measurements, to examine particle deposition in low-shear regions. Such conditions, characteristic of aneurysms, are also prevalent in other flow structures associated with arterial stenosis [23] or any flow separation region [59], such as in the carotid sinus [60]. Furthermore, flow structure features, such as vortices and particle impingement, which may also play an important role in guiding mass deposition in aneurysms, in particular, and in cardiovascular disease, in general, should be further studied in the future.…”

“…Both aneurysm models were coated with collagen (Vitrocol ® , Advanced Biomatrix, see [23] for detailed protocol) to generate a hydrophilic surface and to avoid hydrophobic attraction of the polystyrene particles. The particle deposition pattern was then visualized under a fluorescence microscope (Nikon SMZ 25), and the particles were counted using image processing in MATLAB ® (see electronic supplementary material for the code).…”

“…For example, using the model shown in equation (1.2), Shamloo et al reported that large particles coated with a P-selectin aptamer should have enhanced deposition at the stenosis neck, with little deposition at the post-stenosis zones, where the shear is low [20]. Yet, experimental arterial stenosis models have shown enhanced deposition at the post-stenosis region, where low shear exists [22,23]. Thus, there is a need for a more comprehensive model that incorporates the physics of adhesion at low-shear region, as is the case in side aneurysms.…”

Nanosystems in Cardiovascular Medicine: Advancements, Applications, and Future Perspectives

“…To explore targeted drug delivery in arterial thrombosis, von Willebrand factor (VWF)-A1 domain-functionalized nanoparticles (A1-NPs) have been investigated [ 65 ]. These nanoparticles exhibit flow-structure dependent adhesion to VWF, with preferential localization at post-stenotic regions in coronary stenosis models.…”