Lymphatic Valves Separate Lymph Flow Into a Central Stream and a Slow-Moving Peri-Valvular Milieu

The lymphatic system plays a pivotal role in the transport of fats, waste, and immune cells, while also serving as a metastatic route for select cancers. Using live imaging and particle tracking, we experimentally characterized the lymph flow field distal from the inguinal lymph node in the vicinity of normal bileaflet and malformed unileaflet intraluminal valves. Particle tracking experiments demonstrated that intraluminal lymphatic valves concentrate higher velocity lymph flow in the center of the vessel, while generating adjacent perivalvular recirculation zones. The recirculation zones are characterized by extended particle residence times and low wall shear stress (WSS) magnitudes in comparison to the rest of the lymphangion. A malformed unileaflet valve skewed lymph flow toward the endothelium on the vessel wall, generating a stagnation point and a much larger recirculation zone on the opposite wall. These studies define physical consequences of bileaflet and unileaflet intraluminal lymphatic valves that affect lymph transport and the generation of a heterogeneous flow field that affects the lymphatic endothelium nonuniformly. The characterized flow fields were recreated in vitro connecting different flow environments present in the lymphangion to a lymphatic endothelial cell (LEC) pro-inflammatory phenotype. Unique and detailed insight into lymphatic flow is provided, with potential applications to a variety of diseases that affect lymph transport and drug delivery.