PROJECT SUMMARY/ABSTRACT Nearly 5 million people in the USA suffer from heart failure, with approximately 400,000 heart failure-related deaths occurring yearly. Heart failure causes a significant public healthcare burden and significantly reduces mobility and quality of life. Left ventricular assist device (LVAD) is a promising therapeutic option for end-stage heart failure patients besides cardiac transplant, which is limited by the number of available donors. However, severe complications, including bleeding and thrombosis, significantly worsen the long-term outcome in patients with implanted LVADs. This proposed innovative interdisciplinary effort aims to maximize the LVAD hemocompatibility from two different fronts: hemocompatible slippery hydrophilic (SLIC) coatings and innovative stented inlet design. We hypothesize that by using the SLIC coating and innovative design optimization, the device will achieve excellent hemocompatibility and dramatically reduce blood damage and thrombosis risk. The objective of this project is to develop a novel magnetic levitated (maglev) LVAD with excellent hemocompatibility to reduce thrombosis and complication incidents significantly. After a series of in vitro validation testing and hemocompatibility evaluation, the LVAD prototype will be evaluated and validated in vivo with large animal models. These breakthrough innovations will bring LVAD technology a giant leap forward, eventually crossing the threshold of non-inferior outcomes compared to cardiac transplants. Four aims are proposed to complete this project. In Aim 1 (Optimize SLIC Coatings for Maximum Antithrombotic Response), we will fabricate and characterize the physical and chemical inhomogeneities of SLIC coatings. The coating will cover the entire device, including drive system and inlet cannula. The properties and durability of the coatings will be thoroughly tested. In Aim 2 (Optimize LVAD Design and Develop Novel Stented Inlet to Reduce Thrombosis Risk), we will use a machine learning-based optimization framework and an innovative stented inlet design to reduce blood damage and eliminate the risk of thrombosis at the inlet. The device's hemodynamic performance will be evaluated in vitro by using 2D and 3D particle image velocimetry. In Aim 3 (Design and Evaluate Maglev Drive System with Heart Rate Sensing for Speed Control), we will develop the Maglev drive system to reduce the hemolysis and incorporate it with speed control modulation to reduce the occurrence of regional blood stagnation. Finally, the SLIC LVAD will be validated in Aim 4 (Evaluate In Vitro and In Vivo Hemocompatibility of the Pump Prototype) by both in vitro blood loop experiments and large-animal models for hemocompatibility performance and device energy transmission efficiency. This novel device will potentially be developed as a low-thrombosis-infection-risk therapeutic, a better alternative to cardiac transplant, providing long- term support to end-stage heart failure pat...