Symmetry-breaking flow bifurcation as an under-recognised haemodynamic factor in valve-associated thrombosis

Venous thrombosis commonly develops in the vicinity of venous valve pockets, where disturbed haemodynamics, xreduced washout, and endothelial dysfunction promote thrombus initiation. While previous studies have focused on conventional flow descriptors such as velocity, shear stress, recirculation, and residence time, the influence of valve mechanics on flow organisation remains poorly understood. Here, we combine a biomimetic vein-on-a-chip platform with computational fluid dynamics, fluid-structure interaction simulations, Ghost Particle Velocimetry (GPV), whole-blood flow measurements, and particle transport experiments to investigate the interplay between valve biomechanics and venous haemodynamics. Movable venous valve leaflets fabricated by in situ photopolymerisation of poly(ethylene glycol) diacrylate (PEGDA) enabled independent control of leaflet stiffness under physiologically relevant steady and pulsatile flow conditions. Previous experiments demonstrated that leaflet flexibility governs thrombus localisation, with symmetric leaflet stiffness promoting clot formation at the valve tips, while asymmetric stiffness shifts thrombus formation towards the valve sinus. In addition, we identify a previously undescribed Reynolds-number-dependent symmetry-breaking transition in post-valve flow. Above a critical flow condition, an initially symmetric jet spontaneously develops into a stable asymmetric flow pattern. This behaviour was consistently reproduced experimentally using GPV and confirmed by Fluid-structure simulations. Valve compliance delayed the onset of the transition by increasing the effective leaflet opening, whereas valves with a small geometric offset promoted earlier asymmetry through higher local flow velocities within the valve gap. The resulting asymmetric flow generated persistent lateral bias in the transport of red blood cell-sized particles, suggesting enhanced platelet accumulation and prolonged residence within one valve sinus. These findings demonstrate that venous valve mechanics regulate not only local flow fields but also particle transport relevant to thrombosis. The discovery of a stable symmetry-breaking flow state provides a new haemodynamic mechanism linking valve stiffness, asymmetric particle transport, and the preferential localisation of thrombus formation, offering new insight into the mechanobiology of deep vein thrombosis.