A self-assembled implantable microtubular pacemaker for wireless cardiac electrotherapy

Introduction: The current cardiac pacemakers are battery-dependent, and the pacing leads are prone to introduce valve damage and infection, plus a complete pacemaker retrieval is needed for battery replacement. Despite the reported wireless bioelectronics to pace the epicardium, open-chest (thoracotomy) is required to implant the device, and the procedure is invasive, requiring prolonged wound healing and healthcare burden. We hereby demonstrate a fully biocompatible wireless microelectronics with a self-assembled design that can be rolled into a light-weight microtubular pacemaker for intravascular implantation and pacing. The radiofrequency was employed to transfer energy to the microtubular pacemaker for electrical stimulation. We show that this pacemaker provides effective pacing to restore cardiac contraction from a non-beating heart, and have the capacity to perform overdrive pacing to augment blood circulation in an anesthetized pig model. Thus, this microtubular pacemaker paves the way for the minimally invasive implantation of leadless and battery-free microelectronics.

Materials and

Methods: All chemical reagents were commercially available, including PBS (0.01 M, pH 7.4), xylene from Sigma-Aldrich, USA. Asahi Kasei Corporation provided styrene-ethylene-butylene-styrene (SEBS-H1221) elastomer. As regard the formulation of the SEBS solution for spray coating, 5g SEBS-H1221 elastomer were mixed with 100 ml of xylene and stirred for 5 hours. The gold target (57 X 0.1MM, 99.99%) for sputter coating is purchased from TED PELLA, INC. The polyimide based flexible PCB circuit membrane was designed by the Altium Designer software and fabricated with the help of the PCBWay company, and the thickness of the membrane is about 80 μm.
The flexible PCB (f-PCB) membranes were fabricated by a commercialized PCB manufacturer (PCBWay) based on the designs formed using Altium Designer software. The electrical components for the flexible f-PCB membrane includes capacitors, diodes and voltage doubler CMOS chips. The stimulation electrodes of the f-PCB were sputtered with a layer of gold with a thickness of ~100nm, which have an excellent electrochemical stability in electrolyte environment. A layer of SEBS elastomer encapsulation was coated on the f-PCB through masked-spraying method to further protect the ICs from electrolyte environment but also provide the adhesive property for the following self-assembled rolling process. The thin f-PCB membrane was then rolled into a microtube with a diameter of ~2.5mm. The surface adhesiveness of the SEBS encapsulation contributes to the stable microtubular structure.

Results, Conclusions, and Discussions: A self-assembled implantable microtubular pacemaker was developed for intravascular deployment and wireless pacing to restore cardiovascular function. We demonstrated the battery-free and implantable pacemakers for efficient power transfer and minimal power absorption over an anatomically wireless range. This microtubular pacemaker is promising for intravascular deployment and implantation for the miniatured size to deliver up to DC 5 V to overcome myocardial pacing threshold.
The design of the thin f-PCB film with a SEBS encapsulation enabled a self-assembled rolling process to form the microtubular structure, thus allowing the deployment to the anterior cardiac vein. The magnetic field simulation guided an optimized circuit design to achieve a power transfer efficiency of ~1.3% at distances up to 3 cm. The stimulating electrodes of the microtubular pacemaker are well designed to contact with the endoluminal wall, and the contact area was comparable to that of the distal electrode for the commercially designed leadless pacemaker. The in vivo demonstration on a pig model has further substantiated the functionality of the wireless intravascular pacing methodology via anterior cardiac vein implantation.
The frequency of 1.0 MHz used for our inductive power transfer was to reduce radiation absorption by the bio-tissues and attenuation of power transfer due to the higher frequency band. The inductive power transferring at 1.0 MHz also met the Federal Communication Commission specification for the use of small antennas with low energy. The specific absorption rate was simulated to be ~1.0 x 10-4 W/kg, less than the Federal Drug Administration (FDA)-specified safety level at 10 W/kg. The hemocompatibility of the microtubular pacemaker has been demonstrated via anticoagulation, to reduce the risk of acute thrombosis and immune responses.
Overall, this self-assembled microtubular pacemaker provides an innovative entry point for intravascular deployment with translational implication for cardiac, gastric, neural and urological stimulation. The self-assembled microtubular pacemaker has the capacity to jumpstart a non-beating heart or to perform overdrive pacing from 70 bpm at resting to 120 bpm needed during physical activity. This implementation eliminates the need for a charge storage unit in the bioelectronics, and obviates the need for open-chest thoracotomy, prolonged wound healing, and healthcare burden.

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