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Probing the effect of morphology on lymphatic valve dynamic function

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Abstract

The lymphatic system is vital to the circulatory and immune systems, performing a range of important functions such as transport of interstitial fluid, fatty acid, and immune cells. Lymphatic vessels are composed of contractile walls and lymphatic valves, allowing them to pump lymph against adverse pressure gradients and to prevent backflow. Despite the importance of the lymphatic system, the contribution of mechanical and geometric changes of lymphatic valves and vessels in pathologies of lymphatic dysfunction, such as lymphedema, is not well understood. We develop a fully coupled fluid–solid, three-dimensional computational model to interrogate the various parameters thought to influence valve behavior and the consequences of these changes to overall lymphatic function. A lattice Boltzmann model is used to simulate the lymph, while a lattice spring model is used to model the mechanics of lymphatic valves. Lymphatic valve functions such as enabling lymph flow and preventing backflow under varied lymphatic valve geometries and mechanical properties are investigated to provide an understanding of the function of lymphatic vessels and valves. The simulations indicate that lymphatic valve function is optimized when valves are of low aspect ratio and bending stiffness, so long as these parameters are maintained at high enough values to allow for proper valve closing. This suggests that valve stiffening could have a profound effect on overall lymphatic pumping performance. Furthermore, dynamic valve simulations showed that this model captures the delayed response of lymphatic valves to dynamic flow conditions, which is an essential feature of valve operation. Thus, our model enhances our understanding of how lymphatic pathologies, specifically those exhibiting abnormal valve morphologies such as has been suggested to occur in cases of primary lymphedema, can lead to lymphatic dysfunctions.

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Acknowledgements

Financial support from the National Science Foundation (CMMI-1635133) is gratefully acknowledged. The authors would also like to acknowledge David Zawieja at Texas A&M University for providing access to and assistance with rat isolated lymphatic vessels and John Peroni at the University of Georgia for assistance with obtaining sheep lymphatic vessels.

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Correspondence to Alexander Alexeev.

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Ballard, M., Wolf, K.T., Nepiyushchikh, Z. et al. Probing the effect of morphology on lymphatic valve dynamic function. Biomech Model Mechanobiol 17, 1343–1356 (2018). https://doi.org/10.1007/s10237-018-1030-y

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Keywords

  • Computational simulations
  • Biomechanics
  • Lymphatic valve
  • Lymph transport
  • Lymphedema