Zhiyuan Chen1
The George Washington University1
Zhiyuan Chen1
The George Washington University1
<b>Heart disease kills nearly 700,000 people in the United States each year, with an estimated annual cost of $219 billion.</b> A key factor contributing to these alarming statistics is the lack of tools that can unravel complex pathophysiology, facilitate intraoperative or postsurgical monitoring, and provide effective and timely clinical treatments.<br/><br/>Noble metal–based microelectrode arrays (MEAs) have been widely used to probe the patterns of cardiac excitation waves and identify the regions causing arrhythmias, while electrical pacemakers and defibrillators are the cornerstone of therapy in clinical medicine to correct abnormal heart rhythm. However, they are <b>problematic in detecting critical cardiac parameters</b> such as intracellular calcium dynamics, metabolic activity, or target-specific cell types.<br/><br/>Optical mapping using voltage/calcium-sensitive dyes or intrinsic fluorescence can complement these electrical approaches by uncovering the roles of above-mentioned cellular parameters in both health and disease conditions. However, conventional opaque MEAs are not compatible with this as they block the passage of excitation illumination and fluorescence signals, and obscure the bio-signals by artifacts due to the photovoltaic effect. Furthermore, given the mechanical dynamic nature of hearts, higher requirements are placed on the flexibility of the interface devices. Therefore, developing such technology that can <b>bridge electrophysiology and opto-physiology at cardiac interface is of significance but very challenging</b>.<br/><br/>Soft transparent MEAs show great promise in tackling this challenge, as they allow light to transmit in both directions for simultaneous artifact-free optical and electrical investigation of cell/tissue from the same field of view and visualize the spatiotemporal distribution of cardiac activities with multiple parameters. Additionally, optically transparent MEAs are highly desired during clinical procedures to allow direct observation of areas of interest under the microelectrodes for concurrent optical diagnostics/therapies (such as endoscopy) and guiding other procedures (such as catheters) on the hearts. However, <b>all exsiting transparent MEAs are designed for chronic biointerfacing</b> and require surgical removal when they malfunction or are no longer needed. <br/><br/>In comparison, bioresorbable electronics provide unique opportunities to investigate, monitor, and treat short-lived cardiac complications, including postoperative arrhythmias and heart failure on the order of a few days to weeks following ischemic events or surgery, which account for at least one-third of postoperative deaths. Those devices can subsequently dissolve into benign products via natural metabolic mechanisms to avoid the complications, infection risks, and additional costs associated with surgical retrieval. However, <b>soft transparent MEAs that exhibit bioresorbable functionality remain unexplored</b>.<br/><br/>Here, we report materialas, device design, fabrication, characterization, and validation of <b>the first fully bioresorbable and transparent MEA platform</b>. The developed fabrication strategry achieves <b>nanoscale transient patterns for the first time</b>. The device enables multiparametric electrical and optical mapping of cardiac dynamics and on-demand site-specific stimulation to investigate and modulate cardiac physiology in rat and human heart models. In addition, the device can be used as a heart implant to perform the <b>continuous process of arrhythmia detection, monitoring, and bipolar-pacing treatment</b> <i>in vivo </i>over a clinically relevant period. The bioresorption dynamics and biocompatibility of the device are systematically investigated by histology and serology. The concept and design of this work lay the foundation for bioresorbable cardiac technologies that advance postoperative monitoring and treatment of temporary patient pathological conditions in certain clinical scenarios, such as myocardial infarction, ischemia, and transcatheter aortic valve replacement.