Creation of a Biological Wire using Cell-Targeted Paramagnetic Beads

Abstract

Introduction: Cardiac conduction delays and blocks are associated with re-entrant arrhythmias. We sought to create a novel approach to treat such disorders by engineering biological wires designed to bridge or bypass zones of slow conduction.Methods: Paramagnetic beads (8 μm diameter) were conjugated with an antibody specific for γ-sarcoglycan, a cardiomyocyte cell-surface antigen. Freshly-isolated neonatal rat ventricular cardiomyocytes (NRVMs) were exposed to antibody-coated beads. A biological wire (BioWire) was formed by exposing the bead-NRVM complex to a linear magnetic field. To create a model of conduction block, NRVMs were plated in monolayers and mechanically interrupted along the middle. Action potential (AP) propagation and AP duration were measured by optical mapping.Results: Prior to bridging, the two sides of an interrupted NRVM monolayer beat independently. In order to re-establish conduction, BioWire was formed perpendicular to the axis of interruption, by placing a magnet bridging the two halves underneath the monolayer. Within one day of BioWire implantation, the two NRVM islands beat synchronously, and APs propagated from one island to the other via BioWire with a conduction velocity (CV) of 18±4 cm/s. Action potential morphology and APD90 were similar in BioWire (APD90=443±5ms) and the adjacent monolayers (APD90=439±12ms, p=ns). BioWire was amenable to further engineering. Cardiosphere-derived cells (CDCs), which can couple to and exert anti-apoptotic effects on cardiomyocytes, were mixed with NRVMs and conjugated to the beads via CD105 (≤5% CDCs, BioWire-mx) in order to enhance the physical integrity of BioWire. When paced, BioWire-mx showed faster CV than that of BioWire (17±6 vs 11±1 cm/s, n=4).Conclusion: This proof-of-concept study demonstrates that BioWire could re-establish cardiac conduction between isolated regions of two-dimensional cardiac tissue. The approach is highly generalizable, offering a novel platform to engineer biologically-compatible materials for relaying electrical signals.