Different Effects of Speciesdependent Funny Channel Current on Engineered Biological Pacemaking Activity It has been verified that biological pacemaker could be produced based on ventricular myocytes (VMs) by overexpressing HCN gene which codes the expression of hyperpolarizationactivated current (I f ). Clinically, xenograft is in common use by which one specieu0027 stem cell is infected with another specieu0027s HCN gene so that the stem cell could transfer into cardiac pacemaker cell. The difference of HCN gene between species affects I f  properties, but how the I f  properties influence pacemaker creation is not easy to be qualified in biological experiments. In this study, we build an engineered biological pacemaker model based on a ventricular myocyte model by incorporating I f  formulation and simulated the membrane potential of biological pacemaker. The I f  of different species is simulated by modifying average halfmaximal activation voltage (V 12 ) of I f  activation gate and I f  conductance (G f ). Based on the modified pacemaker model, the effect of I f  properties on pacemaking stability and frequency is evaluated. Simulation results indicate that pacemaking ability is influenced dramatically by I f  properties. In addition, the spontaneous pacemaking mechanism showed both membraneclock and Ca2clock and its deep reason is analyzed in this paper. This study may provide a subcellular perspective for the clinical use of biological pacemaker.

An organosynthetic dynamic heart model with enhanced biomimicry guided by cardiac diffusion tensor imaging The complex motion of the beating heart is accomplished by the spatial arrangement of contracting cardiomyocytes with varying orientation across the transmural layers, which is difficult to imitate in organic or synthetic models. Highfidelity testing of intracardiac devices requires anthropomorphic, dynamic cardiac models that represent this complex motion while maintaining the intricate anatomical structures inside the heart. In this work, we introduce a biorobotic hybrid heart that preserves organic intracardiac structures and mimics cardiac motion by replicating the cardiac myofiber architecture of the left ventricle. The heart model is composed of organic endocardial tissue from a preserved explanted heart with intact intracardiac structures and an active synthetic myocardium that drives the motion of the heart. Inspired by the helical ventricular myocardial band theory, we used diffusion tensor magnetic resonance imaging and tractography of an unraveled organic myocardial band to guide the design of individual soft robotic actuators in a synthetic myocardial band. The active soft tissue mimic was adhered to the organic endocardial tissue in a helical fashion using a customdesigned adhesive to form a flexible, conformable, and watertight organosynthetic interface. The resulting biorobotic hybrid heart simulates the contractile motion of the native heart, compared with in vivo and in silico heart models. In summary, we demonstrate a unique approach fabricating a biomimetic heart model with faithful representation of cardiac motion and endocardial tissue anatomy. These innovations represent important advances toward the unmet need for a highfidelity in vitro cardiac simulator for preclinical testing of intracardiac devices.