Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea.
School of Mechanical Engineering, Pusan National University, Busan 46241, Republic of Korea.
Department of Systems Biotechnology, Chung-Ang University, Ansung 17546, Republic of Korea.
Abstract
Cardiovascular diseases, such as ventricular arrhythmias and heart failure, require timely and effective treatment to prevent disease progression and improve patient outcomes. Current therapeutics, including electrical shock and emergent cardiovascular medications, have significantly contributed to managing these conditions. However, due to their systemic side effects, there are ongoing demands for highly effective localized therapies. In this regard, a soft implantable device has been considered for cardiac applications, but invasiveness in their implantation procedure and difficulty in compact integration of multiple functions are unmet challenges. To address these issues, we develop a stretchable, multi-functional fiber designed for emergent cardiac intervention, offering electrogram recording, electrical modulation, and drug therapy directly at the epicardial surface. With temperature-dependent phase shifting properties of the liquid metal inside the fiber, the stiffened fiber can be implanted into the thoracic cavity without invasive surgery. Once implanted, the softened fiber provides multimodal therapies (e.g., chemotherapy and electrical therapy) tailored to the patient's condition. By tuning the delivery parameters based on continuous electrogram recording, effective and urgent cardiac interventions for severe arrhythmias are demonstrated in an in vivo rat model.
FIG. 1.Device configuration and operating mechanism. (a) The stretchable, cylindrical-shaped fiber, composed of a tri-layer structure, is characterized as follows: (i) a cross-sectional optical microscopic image features inner composition. (ii) The elastomeric outer shell, which consists of a composite of silver–gold core-shell nanowires and SBS polymer, encapsulates (iii) the liquid metal core (eutectic gallium–indium) with a centrally positioned microfluidic channel. The liquid metal transitions between a frozen and liquid state depending on the temperature, enabling minimally invasive implantation. (b) The conductive body and integrated drug channel enable three primary functions, electrogram recording, electrical modulation, and drug delivery. (c) In cardiac emergencies, the frozen fiber rapidly penetrates tissues and transitions to a low-modulus state due to the adaptive modulus properties of the liquid metal. The transition allows the fiber to conform to the epicardial surface. By simultaneously offering multiple operations, the device facilitates effective and immediate therapy.FIG. 2.The schematic illustrating materials and fabrication process. (a) The material requirements for synthesizing the nanocomposite solution and the eutectic gallium–indium alloy as a liquid metal. (b) Fabrication of a microfluidic channel by Ecoflex casting and (c) a customized PDMS mold structure for the outer frame. (d) Step-by-step integration of nanocomposite outer frame, liquid metal, and prepared channel to complete the fabrication of the fiber.FIG. 3.Mechanical, electrical, and electrochemical characteristics as stretchable bioelectronics. (a) Von mises stress distribution illustrates the response of the fiber in solidified state and normal state during skin penetration. (b) and (c) The stress–strain curve demonstrates the fiber's behavior under load in both states, highlighting key mechanical properties such as elastic modulus and fracture strength. (d) Optical images of the fiber before (inset) and after stretching. (e)–(g) Relative resistance changes (R/R0) during strain testing and cyclic stretching reveal the strain-insensitive electrical properties of the fiber. (h) Electrochemical tests verify the stability and functional capabilities of the fiber as a bioelectronics device. (i) The marginal difference in impedance around 1000 Hz, even after 5 h of exposure to PBS, indicates impedance stability. (j) The current density of the conductive nanocomposite electrode, induced by voltage pulses, demonstrates charge injection capacity, while (k) cyclic voltammetry present charge storage capacity, further showcasing the potential as an electrode.FIG. 4.Fluidic delivery ex vivo demonstration and performance evaluation. (a) The process of minimally invasive implantation using freeze spraying. (b) The multiple drug delivery is validated in an ex vivo experiment using 1 wt% agarose gel. (c) The end of the fiber is sharpened like conventional needle, allowing for easy penetration. (d) A syringe pump is used to maintain constant pressure, and (e) the fiber achieves a flow rate similar to a conventional syringe, depending on the applied pressure. (f) The fiber maintains a consistent flow rate under various bending radius and (g) across different stretching cycles.FIG. 5.Cardiac application of the fiber in terms of recording and electroceutical functionality. (a) Schematic illustration demonstrating the setup of an in vivo rat model experiment, highlighting simultaneous electrogram recording and electrical stimulation. Optical endoscope image captured during minimally invasive fiber implantation: (b) before implantation, (c) during implantation, and (d) showing secure contact with the heart. (e) Comparison of the recorded epicardial electrogram's intensity with skin ECG. (f) Epicardial electrograms of normal heart, bradycardia, and during pacing. (g) Epicardial electrogram during ventricular tachycardia, resynchronization therapy, and post recovery.FIG. 6.In vivo demonstration of drug delivery and performance evaluation. (a) Optical image of the drug administration process: before injection, (b) during first type of drug injection, (c) the second type of drug injection, and (d) the combined type of drug injection. (e) Transitions of the epicardial electrogram observed during sequential delivery of epinephrine, diltiazem and electrical signals. (f) Comparison of the R–R interval between normal and after administration of epinephrine, diltiazem, and electrical stimulation. (g) Instantaneous heart rate changes compared to subcutaneous injection. (h) Transition of the R–R interval over time following injection, based on the injection method. (i) Comparison of response times based on the injection method. The response time is defined as the point when the R–R interval increases to 125% of its baseline value. (j) Disease classification code (MATLAB) and the result when applied to normal, bradycardia, and tachycardia electrogram. By detecting the number of ventricular contractions, the code can accurately classify the manifestation of the arrythmia.
