A Multi-faceted Approach to Cardiac Repair

Abstract

Treatment of heart failure has largely been approached with either a mechanical or biological strategy, but in the past few years, the idea of combining mechanical support and cellular therapy synergistically has emerged as a realistic alternative to heart transplantation. The overarching hypothesis of my work is that both therapeutic approaches can be combined to provide acute assistance, longer term regeneration and reverse remodeling. A vision for this polytherapy is a ventricular assist device that allows therapy to be delivered via an integrated biomaterial liner and enables percutaneous replenishment through inbuilt device conduits. I first develop the building blocks towards this type of therapy. Traditional mechanical assist devices are largely blood-contacting, thereby increasing risk of stroke while biological therapies show promise but have been limited by the poor retention and engraftment of cells in cardiac tissue. I develop an active material that can simulate the motion of the heart using soft robotics techniques. I then use this technology to develop a biomimetic direct cardiac compression (DCC) device that is surgically implanted around the heart. The device is synchronized with the native heartbeat through the use of physiological monitoring and has the ability to assist the heart along its natural force vectors I show that this can improve cardiac output in an in vitro and in vivo model. Next, I compare a panel of biomaterials as cell carriers in an infarcted heart, and demonstrate that they can improve cell retention compared to a saline control. I then develop an implantable system that allows non-invasive, repeated replenishment of cells to an implanted biomaterial on the heart. Finally, building on these advancements, I develop a combined mechanical and biological device that assists the heart while providing a network of refillable reservoirs of therapy at the device/heart interface and show proof-of-concept of this polytherapy in vivo.