Printed elastic membranes for multimodal pacing and recording of human stem-cell-derived cardiomyocytes

Markos Athanasiadis,Francesca Murganti,Ivan R Minev,Olaf Bergmann,Wouter Derks,Volker Busskamp,Christoph Tondera,Dzmitry Afanasenkau

doi:10.1038/s41528-020-0075-z

Abstract

Bioelectronic interfaces employing arrays of sensors and bioactuators are promising tools for the study, repair and engineering of cardiac tissues. They are typically constructed from rigid and brittle materials processed in a cleanroom environment. An outstanding technological challenge is the integration of soft materials enabling a closer match to the mechanical properties of biological cells and tissues. Here we present an algorithm for direct writing of elastic membranes with embedded electrodes, optical waveguides and microfluidics using a commercial 3D printing system and a palette of silicone elastomers. As proof of principle, we demonstrate interfacing of cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs), which are engineered to express Channelrhodopsin-2. We demonstrate electrical recording of cardiomyocyte field potentials and their concomitant modulation by optical and pharmacological stimulation delivered via the membrane. Our work contributes a simple prototyping strategy with potential applications in organ-on-chip or implantable systems that are multi-modal and mechanically soft.

Highlights

Recording and modulation in electrogenic tissues requires engineered systems, such as electrode arrays, microfluidics and optical fibres
We develop an algorithm for direct writing of elastic membranes with embedded electrodes, waveguides and microfluidics (Fig. 1a, b)
We present a technological algorithm for printing membranes with integrated electrodes, optrodes and microfluidics for bioelectronic interfaces

Summary

INTRODUCTION

Recording and modulation in electrogenic tissues requires engineered systems, such as electrode arrays, microfluidics and optical fibres. We print prototype devices for liquid mixing and for organ-on-chip applications These are used to demonstrate optical, pharmacological and electrical pacing and recording of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (Fig. 1c). Fabrication of the electrically conductive fibres follows a similar procedure (Fig. 2b, Supplementary Fig. 2b) In this case, the functional core is formed by a conductive composite as described previously[24]. The finished device is connected to external stimulation and recording instrumentation via standard electrical wires, a silica optical fibre and microfluidic tubing (Supplementary Movie 2). This allows us to place the membrane inside a cell culture incubator and to control its operation from outside. This is because shear stresses are known to activate mechanotransduction pathways resulting in recruitment of additional voltage-gated ion channels to the cell membrane[38]

DISCUSSION

Findings

METHODS