A Novel Hybrid Membrane VAD as First Step Toward Hemocompatible Blood Propulsion.

Heart failure is a raising cause of mortality. Heart transplantation and ventricular assist device (VAD) support represent the only available lifelines for end stage disease. In the context of donor organ shortage, the future role of VAD as destination therapy is emerging. Yet, major drawbacks are connected to the long-term implantation of current devices. Poor VAD hemocompatibility exposes the patient to life-threatening events, including haemorrhagic syndromes and thrombosis. Here, we introduce a new concept of artificial support, the Hybrid Membrane VAD, as a first-of-its-kind pump prototype enabling physiological blood propulsion through the cyclic actuation of a hyperelastic membrane, enabling the protection from the thrombogenic interaction between blood and the implant materials. The centre of the luminal membrane surface displays a rationally-developed surface topography interfering with flow to support a living endothelium. The precast cell layer survives to a range of dynamically changing pump actuating conditions i.e., actuation frequency from 1 to 4 Hz, stroke volume from 12 to 30 mL, and support duration up to 313 min, which are tested both in vitro and in vivo, ensuring the full retention of tissue integrity and connectivity under challenging conditions. In summary, the presented results constitute a proof of principle for the Hybrid Membrane VAD concept and represent the basis for its future development towards clinical validation.

Assessment of the Flow Field in the HeartMate 3 Using Three-Dimensional Particle Tracking Velocimetry and Comparison to Computational Fluid Dynamics.

Flow fields in rotary blood pumps (RBPs) have a significant influence on hemocompatibility. Because flow characteristics vary with flow rate, different operating conditions play a role. Furthermore, turbulence is crucial in the evaluation of blood damage potential, but the level of turbulence in implantable RBPs is still unknown. In this study, we addressed both research aspects and for the first time measured turbulent flow fields in the HeartMate 3 (HM3) at different operating flows. The averaged, three-dimensional velocity field including fluctuating velocity components in a HM3 with a transparent lower housing was measured using three-dimensional particle tracking velocimetry (3D-PTV). In vitro results were compared with computational fluid dynamic (CFD) simulations for two flow cases, representing the lower and upper physiologic flow range (2.7 and 5.7 L/min), using two different turbulence models that account for fluctuating velocity fields: the k-ω shear stress transport and the Reynolds stress model (RSM). The measurements revealed higher mean and turbulent kinetic energies (TKEs) for the low-flow condition especially within the gap beneath the impeller. Computed mean fields agree well with 3D-PTV for both models, but the RSM predicts the TKE levels better than the k-ω model. Computational fluid dynamic results further show wall shear stresses higher than 150 Pa, a commonly used damage threshold, in the bottom gap for the lower flow condition. In conclusion, the low-flow condition was found to be more prone to blood damage. Furthermore, CFD predictions for turbulence must be carefully experimentally validated.

High-frequency operation of pulsatile ventricular assist devices: A computational study on circular and elliptically shaped pumps.

Pulsatile positive displacement pumps as ventricular assist devices were gradually replaced by rotary devices due to their large volume and high adverse event rates. Nevertheless, pulsatile ventricular assist devices might be beneficial with regard to gastrointestinal bleeding and cardiac recovery. Therefore, aim of this study was to investigate the flow field in new pulsatile ventricular assist devices concepts with an increased pump frequency, which would allow lower stroke volumes to reduce the pump size. We developed a novel elliptically shaped pulsatile ventricular assist devices, which we compared to a design based on a circular shape. The pump size was adjusted to deliver similar flow rates at pump frequencies of 80, 160, and 240 bpm. Through a computational fluid dynamics study, we investigated flow patterns, residence times, and wall shear stresses for different frequencies and pump sizes. A pump size reduction by almost 50% is possible when using a threefold pump frequency. We show that flow patterns inside the circular pump are frequency dependent, while they remain similar for the elliptic pump. With slightly increased wall shear stresses for higher frequencies, maximum wall shear stresses on the pump housing are higher for the circular design (42.2 Pa vs 18.4 Pa). The calculated blood residence times within the pump decrease significantly with increasing pump rates. A smaller pump size leads to a slight increase of wall shear stresses and a significant improvement of residence times. Hence, high-frequency operation of pulsatile ventricular assist devices, especially in combination with an elliptical shape, might be a feasible mean to reduce the size, without any expectable disadvantages in terms of hemocompatibility.

A Novel Bioreactor System for the Assessment of Endothelialization on Deformable Surfaces.

The generation of a living protective layer at the luminal surface of cardiovascular devices, composed of an autologous functional endothelium, represents the ideal solution to life-threatening, implant-related complications in cardiovascular patients. The initial evaluation of engineering strategies fostering endothelial cell adhesion and proliferation as well as the long-term tissue homeostasis requires in vitro testing in environmental model systems able to recapitulate the hemodynamic conditions experienced at the blood-to-device interface of implants as well as the substrate deformation. Here, we introduce the design and validation of a novel bioreactor system which enables the long-term conditioning of human endothelial cells interacting with artificial materials under dynamic combinations of flow-generated wall shear stress and wall deformation. The wall shear stress and wall deformation values obtained encompass both the physiological and supraphysiological range. They are determined through separate actuation systems which are controlled based on validated computational models. In addition, we demonstrate the good optical conductivity of the system permitting online monitoring of cell activities through live-cell imaging as well as standard biochemical post-processing. Altogether, the bioreactor system defines an unprecedented testing hub for potential strategies toward the endothelialization or re-endothelialization of target substrates.