Development of a Biological Ventricular Assist Device

Abstract

Background— Engineered heart tissue (EHT) can be generated from cardiomyocytes and extracellular matrix proteins and used to repair local heart muscle defects in vivo. Here, we hypothesized that pouch-like heart muscle constructs can be generated by using a novel EHT-casting technology and applied as heart-embracing cardiac grafts in vivo. Methods and Results— Pouch-like EHTs (inner/outer diameter: 10/12 mm) can be generated mainly from neonatal rat heart cells, collagen type I, and serum containing culture medium. They contain a dense network of connexin 43 interconnected cardiomyocytes and an endo-/epicardial surface lining composed of prolylhydroxylase positive cells. Pouch-like EHTs beat spontaneously and show contractile properties of native heart muscle including positive inotropic responses to calcium and isoprenaline. First implantation studies indicate that pouch-like EHTs can be slipped over uninjured adult rat hearts to completely cover the left and right ventricles. Fourteen days after implantation, EHT-grafts stably covered the epicardial surface of the respective hearts. Engrafted EHTs were composed of matrix and differentiated cardiac muscle as well as newly formed vessels which were partly donor-derived. Conclusions— Pouch-like EHTs can be generated with structural and functional properties of native myocardium. Implantation studies demonstrated their applicability as cardiac muscle grafts, setting the stage for an evaluation of EHT-pouches as biological ventricular assist devices in vivo.