Temporary cardiac pacemakers used in periods of need during surgical recovery involve percutaneous leads and externalized hardware that carry risks of infection, constrain patient mobility and may damage the heart during lead removal. Here we report a leadless, battery-free, fully implantable cardiac pacemaker for postoperative control of cardiac rate and rhythm that undergoes complete dissolution and clearance by natural biological processes after a defined operating timeframe. We show that these devices provide effective pacing of hearts of various sizes in mouse, rat, rabbit, canine and human cardiac models, with tailored geometries and operation timescales, powered by wireless energy transfer. This approach overcomes key disadvantages of traditional temporary pacing devices and may serve as the basis for the next generation of postoperative temporary pacing technology.
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All data that support the findings of this study are included in the manuscript. Source data are provided with this paper.
The software for the analysis of optical mapping data, custom MATLAB software (RHYHTM) and custom scripts used in the study are freely available for download at https://github.com/optocardiography.
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This work made use of the NUFAB facility of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental Resource (NSF no. ECCS-1542205); the MRSEC program (NSF no. DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. This work was also performed in part at The George Washington University Nanofabrication and Imaging Center. We acknowledge support from the Leducq Foundation projects RHYTHM and R01-HL141470 (to I.R.E. and J.A.R.). R.T.Y. acknowledges support from the American Heart Association Predoctoral Fellowship (no. 19PRE34380781). R.A. acknowledges support from the National Science Foundation Graduate Research Fellowship (NSF no. 1842165) and the Ford Foundation Predoctoral Fellowship. Z.X. acknowledges the support from the National Natural Science Foundation of China (grant no. 12072057) and Fundamental Research Funds for the Central Universities (grant no. DUT20RC(3)032). B.P.K. and D.J. acknowledge support from a research donation by Mr and Mrs Ronald and JoAnne Willens. We thank NU Comprehensive Transplant Center Microsurgery Core for help with cardiac implantation surgical procedures. We also thank the Washington Regional Transplant Community, heart organ donors and families of the donors; our research would not have been possible without their generous donations and support.
The authors declare no competing interests.
Peer review information Nature Biotechnology thanks the anonymous reviewers for their contribution to the peer review of this work.
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Extended Data Fig. 1 Illustrations that compare use scenarios of conventional temporary pacemakers and the bioresorbable, implantable, leadless, battery-free devices reported here.
a, Schematic illustration that demonstrates the existing clinical approach for using conventional temporary pacemakers. (i) An external generator connects through wired, percutaneous interfaces to pacing electrodes attached to the myocardium. Temporary transvenous leads are affixed to the myocardium either passively with tines or actively with extendable/retractable screws. (ii) The pacing leads can become enveloped in fibrotic tissue at the electrode-myocardium interface, which increases the risk of myocardial damage and perforation during lead removal. As a result, temporary epicardial leads placed at the time of open heart surgery are often cut and allowed to retract to avoid the risk of removal by traction. b, The proposed approach is uniquely enabled by the bioresorbable, leadless device introduced here. (i) Electrical stimulation paces the heart via inductive wireless power transfer, as needed throughout the post-operative period. (ii) Following resolution of pacing needs or insertion of a permanent device, the implanted device dissolves into the body, thereby eliminating the need for extraction.
Extended Data Fig. 2 Design of bioresorbable, implantable, leadless, battery-free cardiac pacemaker.
a, Dimensions of the device: (top) x,y-view; (bottom) x,z-view. The minimum length of the device is 15.8 mm. The total length can be altered to meet requirements for the target application, simply by changing the length of the extension electrode. b, Dimensions of the contact pad. PLGA encapsulation covers the top surface of the contact electrode to leave only the bottom of contact electrode exposed.
Extended Data Fig. 3 Modeling and experimental studies of mechanical reliability of the bioresorbable, leadless cardiac pacemaker.
a, Photograph (left) and FEA (right) results for devices during compressive buckling (20%). Scale bar, 10 mm. b, c, d, Photograph of twisted (180°) and bent (bend radius = 4 mm) devices. Scale bar, 10 mm. e, Output voltage of a device as a function of bending radius (left), compression (middle), and twist angle (right) at different distances between the Rx and Tx coils (black, 1 mm; red 6 mm). n = 3 independent samples.
a, Schematic illustration of the circuit diagram for the transmission of RF power. Monophasic electrical pulses (programmed duration; alternative current) are generated by a waveform generator at ~13.5 MHz (Agilent 33250 A, Agilent Technologies, USA). The voltage can be further increased with an amplifier (210 L, Electronics & innovation, Ltd., USA). The generated waveforms (that is input power) are delivered to the Tx coil (3 turns, 20 mm diameter). This RF power is transferred to the Mg Rx coil (17 turns, 12 mm diameter) of an implanted bioresorbable cardiac pacemaker. The received waveform is transformed into a direct current output via the RF diode to stimulate the targeted tissue. b, Measured RF behavior of the stimulator (black, S11; red, phase). The resonance frequency is ~13.5 MHz. c, Simulation results for inductance (L) and Q factor as a function of frequency. d, An alternating current (sine wave) applied to the Tx coil. The resonance frequency and input voltage (that is transmitting voltage) are ~13.5 MHz and 7 Vpp, respectively. e, Example direct current output of ~13.2 V wirelessly generated via the Rx coil of the bioresorbable device. f, Output voltage as a function of transmitting frequency. At the resonance frequency (~13.5 MHz) of the receiver coil (transmitting voltage = 7 V), the device produces a maximum output voltage of ~13.2 V. g, Output voltage as a function of the distance between the Tx and Rx coils (transmitting voltage = 10 Vpp; transmitting frequency = ~13.5 MHz).
ECG, optical mapping data.
ECG, optical mapping data.
ECG, output performance data.
Output performance data.
Output performance data.
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Choi, Y.S., Yin, R.T., Pfenniger, A. et al. Fully implantable and bioresorbable cardiac pacemakers without leads or batteries. Nat Biotechnol (2021). https://doi.org/10.1038/s41587-021-00948-x