A Sewing Approach to the Fabrication of Eco/bioresorbable Electronics.

Eco/bioresorbable electronics represent an emerging class of technology defined by an ability to dissolve or otherwise harmlessly disappear in environmental or biological surroundings after a period of stable operation. The resulting devices provide unique capabilities as temporary biomedical implants, environmental sensors, and related systems. Recent publications report schemes to overcome challenges in fabrication that follow from the low thermostability and/or high chemical reactivity of the eco/bioresorbable constituent materials. Here, this work reports the use of high-speed sewing machines, as the basis for a high-throughput manufacturing technique that addresses many requirements for these applications, without the need for high temperatures or reactive solvents. Results demonstrate that a range of eco/bioresorbable metal wires and polymer threads can be embroidered into complex, user-defined conductive patterns on eco/bioresorbable substrates. Functional electronic components, such as stretchable interconnects and antennas are possible, along with fully integrated systems. Examples of the latter include wirelessly powered light-emitting diodes, radiofrequency identification tags, and temporary cardiac pacemakers. These advances add to a growing range of options in high-throughput, automated fabrication of eco/bioresorbable electronics.

Soft, bioresorbable, transparent microelectrode arrays for multimodal spatiotemporal mapping and modulation of cardiac physiology.

Transparent microelectrode arrays (MEAs) that allow multimodal investigation of the spatiotemporal cardiac characteristics are important in studying and treating heart disease. Existing implantable devices, however, are designed to support chronic operational lifetimes and require surgical extraction when they malfunction or are no longer needed. Meanwhile, bioresorbable systems that can self-eliminate after performing temporary functions are increasingly attractive because they avoid the costs/risks of surgical extraction. We report the design, fabrication, characterization, and validation of a soft, fully bioresorbable, and transparent MEA platform for bidirectional cardiac interfacing over a clinically relevant period. The MEA provides multiparametric electrical/optical mapping of cardiac dynamics and on-demand site-specific pacing to investigate and treat cardiac dysfunctions in rat and human heart models. The bioresorption dynamics and biocompatibility are investigated. The device designs serve as the basis for bioresorbable cardiac technologies for potential postsurgical monitoring and treating temporary patient pathological conditions in certain clinical scenarios, such as myocardial infarction, ischemia, and transcatheter aortic valve replacement.

Wireless, fully implantable cardiac stimulation and recording with on-device computation for closed-loop pacing and defibrillation.

Monitoring and control of cardiac function are critical for investigation of cardiovascular pathophysiology and developing life-saving therapies. However, chronic stimulation of the heart in freely moving small animal subjects, which offer a variety of genotypes and phenotypes, is currently difficult. Specifically, real-time control of cardiac function with high spatial and temporal resolution is currently not possible. Here, we introduce a wireless battery-free device with on-board computation for real-time cardiac control with multisite stimulation enabling optogenetic modulation of the entire rodent heart. Seamless integration of the biointerface with the heart is enabled by machine learning-guided design of ultrathin arrays. Long-term pacing, recording, and on-board computation are demonstrated in freely moving animals. This device class enables new heart failure models and offers a platform to test real-time therapeutic paradigms over chronic time scales by providing means to control cardiac function continuously over the lifetime of the subject.

Acetylcholine Reduces IKr and Prolongs Action Potentials in Human Ventricular Cardiomyocytes.

Vagal nerve stimulation (VNS) has a meaningful basis as a potentially effective treatment for heart failure with reduced ejection fraction. There is an ongoing VNS randomized study, and four studies are completed. However, relatively little is known about the effect of acetylcholine (ACh) on repolarization in human ventricular cardiomyocytes, as well as the effect of ACh on the rapid component of the delayed rectifier K+ current (IKr). Here, we investigated the effect of ACh on the action potential parameters in human ventricular preparations and on IKr in human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Using standard microelectrode technique, we demonstrated that ACh (5 µM) significantly increased the action potential duration in human left ventricular myocardial slices. ACh (5 µM) also prolonged repolarization in a human Purkinje fiber and a papillary muscle. Optical mapping revealed that ACh increased the action potential duration in human left ventricular myocardial slices and that the effect was dose-dependent. Perforated patch clamp experiments demonstrated action potential prolongation and a significant decrease in IKr by ACh (5 µM) in hiPSC-CMs. Computer simulations of the electrical activity of a human ventricular cardiomyocyte showed an increase in action potential duration upon implementation of the experimentally observed ACh-induced changes in the fully activated conductance and steady-state activation of IKr. Our findings support the hypothesis that ACh can influence the repolarization in human ventricular cardiomyocytes by at least changes in IKr.

Advances in Implantable Optogenetic Technology for Cardiovascular Research and Medicine.

Optogenetic technology provides researchers with spatiotemporally precise tools for stimulation, sensing, and analysis of function in cells, tissues, and organs. These tools can offer low-energy and localized approaches due to the use of the transgenically expressed light gated cation channel Channelrhodopsin-2 (ChR2). While the field began with many neurobiological accomplishments it has also evolved exceptionally well in animal cardiac research, both in vitro and in vivo. Implantable optical devices are being extensively developed to study particular electrophysiological phenomena with the precise control that optogenetics provides. In this review, we highlight recent advances in novel implantable optogenetic devices and their feasibility in cardiac research. Furthermore, we also emphasize the difficulties in translating this technology toward clinical applications and discuss potential solutions for successful clinical translation.