Ex vivo lymphatic perfusion system for independently controlling pressure gradient and transmural pressure in...

In addition to external forces, collecting lymphatic vessels intrinsically contract to transport lymph from the extremities to the venous circulation. As a result, the lymphatic endothelium is routinely exposed to a wide range of dynamic mechanical forces, primarily fluid shear stress and circumferential stress, which have both been shown to affect lymphatic pumping activity. Although various ex vivo perfusion systems exist to study this innate pumping activity in response to mechanical stimuli, none are capable of independently controlling the two primary mechanical forces affecting lymphatic contractility: transaxial pressure gradient, [Formula: see text], which governs fluid shear stress; and average transmural pressure, [Formula: see text], which governs circumferential stress. Hence, the authors describe a novel ex vivo lymphatic perfusion system (ELPS) capable of independently controlling these two outputs using a linear, explicit model predictive control (MPC) algorithm. The ELPS is capable of reproducing arbitrary waveforms within the frequency range observed in the lymphatics in vivo, including a time-varying [Formula: see text] with a constant [Formula: see text], time-varying [Formula: see text] and [Formula: see text], and a constant [Formula: see text] with a time-varying [Formula: see text]. In addition, due to its implementation of syringes to actuate the working fluid, a post-hoc method of estimating both the flow rate through the vessel and fluid wall shear stress over multiple, long (5 s) time windows is also described.