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.
Waldo, A. L., Wells, J. L. J., Cooper, T. B. & MacLean, W. A. Temporary cardiac pacing: applications and techniques in the treatment of cardiac arrhythmias. Prog. Cardiovasc. Dis. 23, 451–474 (1981).
Zoll, P. M. et al. External noninvasive temporary cardiac pacing: clinical trials. Circulation 71, 937–944 (1985).
Curtis, J. J. et al. A critical look at temporary ventricular pacing following cardiac surgery. Surgery 82, 888–893 (1977).
Wilhelm, M. J. et al. Cardiac pacemaker infection: surgical management with and without extracorporeal circulation. Ann. Thorac. Surg. 64, 1707–1712 (1997).
Choo, M. H. et al. Permanent pacemaker infections: characterization and management. Am. J. Cardiol. 48, 559–564 (1981).
Imparato, A. M. & Kim, G. E. Electrode complications in patients with permanent cardiac pacemakers. Arch. Surg. 105, 705–710 (1972).
Bernstein, V., Rotem, C. E. & Peretz, D. I. Permanent pacemakers: 8-year follow-up study. Incidence and management of congestive cardiac failure and perforations. Ann. Intern. Med. 74, 361–369 (1971).
Hartstein, A. I., Jackson, J. & Gilbert, D. N. Prophylactic antibiotics and the insertion of permanent transvenous cardiac pacemakers. J. Thorac. Cardiovasc. Surg. 75, 219–223 (1978).
Austin, J. L., Preis, L. K., Crampton, R. S., Beller, G. A. & Martin, R. P. Analysis of pacemaker malfunction and complications of temporary pacing in the coronary care unit. Am. J. Cardiol. 49, 301–306 (1982).
Lumia, F. J. & Rios, J. C. Temporary transvenous pacemaker therapy: an analysis of complications. Chest 64, 604–608 (1973).
Donovan, K. D. & Lee, K. Y. Indications for and complications of temporary transvenous cardiac pacing. Anaesth. Intensive Care 13, 63–70 (1985).
Braun, M. U. et al. Percutaneous lead implantation connected to an external device in stimulation-dependent patients with systemic infection – a prospective and controlled study. Pacing Clin. Electrophysiol. 29, 875–879 (2006).
Del Nido, P. & Goldman, B. S. Temporary epicardial pacing after open heart surgery: complications and prevention. J. Card. Surg. 4, 99–103 (1989).
Elmistekawy, E. Safety of temporary pacemaker wires. Asian Cardiovasc. Thorac. Ann. 27, 341–346 (2019).
Gutruf, P. et al. Wireless, battery-free, fully implantable multimodal and multisite pacemakers for applications in small animal models. Nat. Commun. 10, 5742 (2019).
Koo, J. et al. Wireless bioresorbable electronic system enables sustained nonpharmacological neuroregenerative therapy. Nat. Med. 24, 1830–1836 (2018).
Choi, Y. S. et al. Stretchable, dynamic covalent polymers for soft, long-lived bioresorbable electronic stimulators designed to facilitate neuromuscular regeneration. Nat. Commun. 11, 5990 (2020).
Won, S. M. et al. Natural wax for transient electronics. Adv. Funct. Mater. 28, 1801819 (2018).
Choi, Y. S., Koo, J. & Rogers, J. A. Inorganic materials for transient electronics in biomedical applications. MRS Bull. 45, 103–112 (2020).
Makadia, H. K. & Siegel, S. J. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers (Basel) 3, 1377–1397 (2011).
Hwang, S. W. et al. Dissolution chemistry and biocompatibility of single-crystalline silicon nanomembranes and associated materials for transient electronics. ACS Nano 8, 5843–5851 (2014).
Yin, L. et al. Mechanisms for hydrolysis of silicon nanomembranes as used in bioresorbable electronics. Adv. Mater. 27, 1857–1864 (2015).
Yin, L. et al. Dissolvable metals for transient electronics. Adv. Funct. Mater. 24, 645–658 (2014).
Length, F. Chemical and structural characterization of Candelilla (Euphorbia antisyphilitica Zucc.). J. Med. Plants Res. 7, 702–705 (2013).
Winter, K. F., Hartmann, R. & Klinke, R. A stimulator with wireless power and signal transmission for implantation in animal experiments and other applications. J. Neurosci. Methods 79, 79–85 (1998).
Dinis, H., Colmiais, I. & Mendes, P. M. Extending the limits of wireless power transfer to miniaturized implantable electronic devices. Micromachines 8, 359 (2017).
Kang, S. K. et al. Bioresorbable silicon electronic sensors for the brain. Nature 530, 71–76 (2016).
Shreiner, D. P., Weisfeldt, M. L. & Shock, N. W. Effects of age, sex, and breeding status on the rat heart. Am. J. Physiol. Content 217, 176–180 (1969).
Mačianskienė, R. et al. Evaluation of excitation propagation in the rabbit heart: optical mapping and transmural microelectrode recordings. PLoS ONE 10, e0123050 (2015).
Lee, P. T. et al. Left ventricular wall thickness and the presence of asymmetric hypertrophy in healthy young army recruits. Circ. Cardiovasc. Imaging 6, 262–267 (2013).
Schwartzman, D., Chang, I., Michele, J. J., Mirotznik, M. S. & Foster, K. R. Electrical impedance properties of normal and chronically infarcted left ventricular myocardium. J. Interv. Card. Electrophysiol. 3, 213–224 (1999).
Salazar, Y., Bragos, R., Casas, O., Cinca, J. & Rosell, J. Transmural versus nontransmural in situ electrical impedance spectrum for healthy, ischemic, and healed myocardium. IEEE Trans. Biomed. Eng. 51, 1421–1427 (2004).
Clauss, S. et al. Animal models of arrhythmia: classic electrophysiology to genetically modified large animals. Nat. Rev. Cardiol. 16, 457–475 (2019).
Pichorim, S. F. Design of circular and solenoid coils for maximum mutual inductance. In Proc.14th International Symposium on Biotelemetry 71–77 (Tectum, 1998).
Kurs, A. et al. Wireless power transfer via strongly coupled magnetic resonances. Science 317, 83–86 (2007).
Rahko, P. S. Evaluation of the skin-to-heart distance in the standing adult by two-dimensional echocardiography. J. Am. Soc. Echocardiogr. 21, 761–764 (2008).
C95.1-2005 IEEE Standard for Safety Levels with Respect to Human Exposure to Radio Frequency Electromagnetic Fields, 3 kHz to 300 GHz (revision of IEEE Std C95.1-1991). https://doi.org/10.1109/IEEESTD.2006.99501 (2006).
Choi, Y. S. et al. Biodegradable polyanhydrides as encapsulation layers for transient electronics. Adv. Funct. Mater. 30, 2000941 (2020).
Koo, J. et al. Wirelessly controlled, bioresorbable drug delivery devices with active valves that exploit electrochemically triggered crevice corrosion. Sci. Adv. 6, eabb1093 (2020).
Katsura, M., Sato, J., Akahane, M., Kunimatsu, A. & Abe, O. Current and novel techniques for metal artifact reduction at CT: practical guide for radiologists. Radiographics 38, 450–461 (2018).
Lee, Y. K. et al. Dissolution of monocrystalline silicon nanomembranes and their use as encapsulation layers and electrical interfaces in water-soluble electronics. ACS Nano 11, 12562–12572 (2017).
Sofia, S. J., Premnath, V. & Merrill, E. W. Poly(ethylene oxide) grafted to silicon surfaces: grafting density and protein adsorption. Macromolecules 31, 5059–5070 (1998).
Nakanishi, K., Sakiyama, T. & Imamura, K. On the adsorption of proteins on solid surfaces, a common but very complicated phenomenon. J. Biosci. Bioeng. 91, 233–244 (2001).
Lee, G., Choi, Y. S., Yoon, H.-J. & Rogers, J. A. Advances in physicochemically stimuli-responsive materials for on-demand transient electronic systems. Matter 3, 1031–1052 (2020).
Sperelakis, N. & Hoshiko, T. Electrical impedance of cardiac muscle. Circ. Res. 9, 1280–1283 (1961).
Fry, C. H. et al. Cytoplasm resistivity of mammalian atrial myocardium determined by dielectrophoresis and impedance methods. Biophys. J. 103, 2287–2294 (2012).
Gabriel, S., Lau, R. W. & Gabriel, C. The dielectric properties of biological tissues: II. Measurements in the frequency range 10 Hz to 20 GHz. Phys. Med. Biol. 41, 2251–2269 (1996).
Rong, C. et al. Analysis of wireless power transfer based on metamaterial using equivalent circuit. J. Eng. 2019, 2032–2035 (2019).
George, S. A., Brennan, J. A. & Efimov, I. R. Preclinical cardiac electrophysiology assessment by dual voltage and calcium optical mapping of human organotypic cardiac slices. J. Vis. Exp. https://doi.org/10.3791/60781 (2020).
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 39, 1228–1238 (2021). https://doi.org/10.1038/s41587-021-00948-x
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