We investigate the mechanical conditions leading to the rupture of the plasma membrane of an endothelial cell subjected to a local, compressive force. Membrane rupture is induced by tilted microindentation, a technique used to perform mechanical measurements on adherent cells. In this technique, the applied force can be deduced from the measured horizontal displacement of a microindenter's tip, as imaged with an inverted microscope and without the need for optical sensors to measure the microindenter's deflection. We show that plasma membrane rupture of endothelial cells occurs at a well-defined value of the applied compressive stress. As a point of reference, we use numerical simulations to estimate the magnitude of the compressive stresses exerted on endothelial cells during the deployment of a stent.

Purpose-Wave membrane blood pumps (WMBP) are novel pump designs in which blood is propelled by means of wave propagation by an undulating membrane. In this paper, we computationally studied the performance of a new WMBP design (J-shaped) for different working conditions, in view of potential applications in human patients. Methods-Fluid-structure interaction (FSI) simulations were conducted in 3D pump geometries and numerically discretized by means of the extended finite element method (XFEM). A contact model was introduced to capture membrane-wall collisions in the pump head. Mean flow rate and membrane envelope were determined to evaluate hydraulic performance. A preliminary hemocompatibility analysis was performed via calculation of fluid shear stress. Results-Numerical results, validated against in vitro experimental data, showed that the hydraulic output increases when either the frequency or the amplitude of membrane oscillations were higher, with limited increase in the fluid stresses, suggesting good hemocompatibility properties. Also, we showed better performance in terms of hydraulic power with respect to a previous design of the pump. We finally studied an operating point which achieves physiologic flow rate target at diastolic head pressure of 80 mmHg. Conclusion-A new design of WMBP was computationally studied. The proposed FSI model with contact was employed to predict the new pump hydraulic performance and it could help to properly select an operating point for the upcoming first-in-human trials.

Background: Lack of physiologic pulsatility with the use of continuous flow (CF) LVADs has been associated with serious adverse events including stroke, bleeding, and aortic insufficiency. CorWave is developing a unique LVAD employing an undulating membrane to generate a physiologic pulse while improving hemocompatibility. The present studies focused on in vitro and in vivo testing of the pump control algorithms for hemodynamic performance and hemocompatibility. Methods: The pump actuator, membrane, and blood flow path were designed using respectively electromagnetic simulations (MAGNET), Fluid-Structure Interaction (COMSOL), and Computational Fluid Dynamics. Algorithms were developed for actuator control, synchronization with the native left ventricle (LV), suction detection, and adaptive physiologic control. They were tested in a mock circulation loop (MCL) with INTERMACS 1-2, 3-4, and 5-6 heart failure (HF) profiles using LV pressure-volume loops to examine performance. The algorithms were then tested in chronic implants in healthy sheep for up to 3 months, and in acute implants in sheep with induced HF (ejection fraction < 40%). Results: During MCL tests, in synchronous pulsation (SynchPuls) mode, the membrane pump generated a more physiologic PV loop, with lower mean left atrial pressures (LAP), increased native LV stroke volume, and 1:1 opening of the aortic valve. CF pumps generated a characteristic, non-physiologic narrow PV loop with elevated mean LAP and aortic valve opening once per 3-5 beats. These results demonstrated the SynchPuls algorithm could respond to changes in pre-load to better unload the LV, restore more physiologic hemodynamics, and ensure aortic valve opening, so we proceeded to animal trials, which present more dynamic and challenging conditions. During acute implants in sheep with HF, using SynchPuls, the membrane pump increased cardiac output from ~2 to ~4 LPM. The physiologic control algorithm adjusted pump output to prevent LV suction and retrograde flow during hemodynamic manipulations, including epinephrine administration, and head up or down tilt. The algorithms switched to continuous mode, as intended, when arrhythmias or tachycardia were detected. In chronic implants, the SynchPuls algorithm successfully synchronized with the LV for > 97% of heartbeats and adapted to circadian cycles. Biomarkers of end-organ function returned to baseline within 2 weeks of implant, hemolysis was < 20 mg/dL, and VWF activity was preserved during the chronic implants. Conclusion: These studies showed that the membrane pump can provide physiologic pulsatility and restore cardiac output in HF models. The algorithms' robustness was confirmed in chronic implants. Overall, these successful tests demonstrated that the CorWave membrane pump can deliver the hemocompatibility, pulsatility, and adaptability required to advance the LVAD field. CARD20