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The lymphatics transport material from peripheral tissues to lymph nodes, where immune responses are formed, before being transported into systemic circulation. With key roles in transport and fluid homeostasis, lymphatic dysregulation is linked to diseases, including lymphedema. Fluid within the interstitium passes into initial lymphatic vessels where a valve system prevents fluid backflow. Additionally, lymphatic endothelial cells produce key chemokines, such as CCL21, that direct the migration of dendritic cells and lymphocytes. As a result, lymphatics are an attractive delivery route for transporting immune modulatory treatments to lymph nodes where immunotherapies are potentiated in addition to being an alternative method of reaching systemic circulation. In this review, we discuss the physiology of lymphatic vessels and mechanisms used in the transport of materials from peripheral tissues to lymph nodes. We then summarize nanomaterial-based strategies to take advantage of lymphatic transport functions for delivering therapeutics to lymph nodes or systemic circulation. We also describe opportunities for targeting lymphatic endothelial cells to modulate transport and immune functions.
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Fluid pumping of peristaltic vessel fitted with elastic valves
Using numerical simulations, we probe the fluid flow in an axisymmetric peristaltic vessel fitted with elastic bi-leaflet valves. In this biomimetic system that mimics the flow generated in lymphatic vessels, we investigate the effects of the valve and vessel properties on pumping performance of the valved peristaltic vessel. The results indicate that valves significantly increase pumping by reducing backflow. The presence of valves, however, increases the viscous resistance, therefore requiring greater work compared to valveless vessels. The benefit of the valves is the most significant when the fluid is pumped against an adverse pressure gradient and for low vessel contraction wave speeds. We identify the optimum vessel and valve parameters leading to the maximum pumping efficiency. We show that the optimum valve elasticity maximizes the pumping flow rate by allowing the valve to block the backflow more effectively while maintaining low resistance during the forward flow. We also examine the pumping in vessels where the vessel contraction amplitude is a function of the adverse pressure gradient, as found in lymphatic vessels. We find that, in this case, the flow is limited by the work generated by the contracting vessel, suggesting that the pumping in lymphatic vessels is constrained by the performance of the lymphatic muscle. Given the regional heterogeneity of valve morphology observed throughout the lymphatic vasculature, these results provide insight into how these variations might facilitate efficient lymphatic transport in the vessel's local physiologic context.
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- Award ID(s):
- 1635133
- PAR ID:
- 10283099
- Date Published:
- Journal Name:
- Journal of Fluid Mechanics
- Volume:
- 918
- ISSN:
- 0022-1120
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1017/jfm.2021.302
