Abstract
Temporary pacemakers are essential for the care of patients with short-lived bradycardia in post-operative and other settings1,2,3,4. Conventional devices require invasive open-heart surgery or less invasive endovascular surgery, both of which are challenging for paediatric and adult patients5,6,7,8. Other complications9,10,11 include risks of infections, lacerations and perforations of the myocardium, and of displacements of external power supplies and control systems. Here we introduce a millimetre-scale bioresorbable optoelectronic system with an onboard power supply and a wireless, optical control mechanism with generalized capabilities in electrotherapy and specific application opportunities in temporary cardiac pacing. The extremely small sizes of these devices enable minimally invasive implantation, including percutaneous injection and endovascular delivery. Experimental studies demonstrate effective pacing in mouse, rat, porcine, canine and human cardiac models at both single-site and multi-site locations. Pairing with a skin-interfaced wireless device allows autonomous, closed-loop operation upon detection of arrhythmias. Further work illustrates opportunities in combining these miniaturized devices with other medical implants, with an example of arrays of pacemakers for individual or collective use on the frames of transcatheter aortic valve replacement systems, to provide unique solutions that address risks for atrioventricular block following surgeries. This base technology can be readily adapted for a broad range of additional applications in electrotherapy, such as nerve and bone regeneration, wound therapy and pain management.
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Data availability
The data supporting the results of this study are present in the paper and Supplementary Information. Source data are provided with this paper.
Code availability
The code for connecting to the device via BLE, recording and analysing ECG data in real time, and configuring the pacing parameters in a closed-loop system is available on Code Ocean at https://codeocean.com/capsule/9406347/tree/v1 (ref. 49).
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Acknowledgements
We acknowledge support from the Querrey Simpson Institute for Bioelectronics, the Leducq Foundation grant ‘Bioelectronics for Neurocardiology’ and the NIH grant (NIH R01 HL141470). Y.Z. acknowledges support from the National University of Singapore start-up grant and the AHA’s Second Century Early Faculty Independence Award (grant: https://doi.org/10.58275/AHA.23SCEFIA1154076.pc.gr.173925). J. Gong and Z.M. acknowledge the support from AFOSR (grant number FA9550-21-1-0081). We thank E. Dempsey, Q. Ma, N. Ghoreishi-Haack, I. Stepien and S. Han for the help in the biocompatibility study and animal experiment. This work made use of the NUFAB facility of Northwestern University’s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), the IIN and Northwestern’s MRSEC programme (NSF DMR-1720139). This work was supported by the Developmental Therapeutics Core and the Center for Advanced Molecular Imaging (RRID:SCR_021192) at Northwestern University and the Robert H. Lurie Comprehensive Cancer Center support grant (NCI P30 CA060553).
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Contributions
Y.Z. and J.A.R. initiated and conceived the self-powered, light-controlled pacing concept. Y.Z., E.R., I.R.E. and J.A.R. designed the studies and analysed the results. Y.Z., L.Z., K.Z., X.L., A.L., G.J., J.L., F.L., Y.F.L.L., Y.L., C.H., A.H. and R.N. fabricated and characterized the pacemakers. E.R., L.T., A. Mikhailov, L.D., A.B., A.P., A.A. and A. Melisova conducted animal surgeries. Y.Z., E.R., L.Z., L.T., A. Mikhailov, L.D., J.W., A.B., A.P. and W.O., performed in vivo and ex vivo cardiac pacing experiments. W.O., Y.W., J. Gu, T.Y., Y.Y. and Y.L. developed closed-loop and optical control systems. J.U.K., S.G.S., J. Gong, J.J., J.C., S.H.J. and Z.M. designed and fabricated phototransistors. H.Z., S.L., Z.L. and Y.H. performed computational simulations. E.A. and W.B. fabricated bioresorbable optical filters. T.W., N.S.P. and J.M.T. developed and synthesized the hydrogels. L.T., L.D. and K.B. evaluated the biocompatibility. Y.Z., E.R., L.Z., J.U.K., L.T., A. Mikhailov., K.Z., X.L., Y.W., H.Z., A.L., E.A., G.J., S.L., S.G.S., K.B., N.L., W.O., R.K.A., I.R.E. and J.A.R. discussed and interpreted the data. Y.Z. and J.A.R. prepared figures and wrote the paper, with input from E.R., W.O., A. Mikhailov, R.K.A. and I.R.E. In addition, J.U.K., L.Z., L.T., Y.W., H.Z., S.L. and J. Gu. assisted with the preparation of figures and text. Y.Z., L.Z., L.T., H.Z., L.D., W.O., I.R.E. and J.A.R. revised the paper. Y.Z., E.R., L.Z., J.U.K., L.T. and H.Z. contributed equally to this work.
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Extended data figures and tables
Extended Data Fig. 1 Comparisons of previously reported pacemakers and the technology introduced here.
a, Comparisons between conventional pacemakers with leads, leadless pacemakers, bioresorbable pacemakers, and the pacemaker reported here. b, Table showing details of previously reported leadless pacemakers and the pacemaker reported here. Illustration of the pacemaker with leads in a was created with BioRender.com (https://biorender.com). Bioresorbable pacemaker in a adapted from ref. 1, Springer Nature America, Inc.
Extended Data Fig. 2 Characteristics of bipolar junction transistor (BJT)-based phototransistors.
a,b, Characteristic curves of the phototransistors under various light intensities emitted from a NIR LED (850 nm, a) and a red LED (650 nm, b).
Extended Data Fig. 3 Measurement of the operational lifespan of the device.
a, EIS of an agarose gel and chicken tissue. b, The output currents of the pacemaker over days. c, Output currents of the pacemaker over days under pulsed illumination.
Extended Data Fig. 4 In vivo demonstration of cardiac pacing in mouse models.
a, Photograph showing a pacemaker placed on the surface of a mouse heart. b, ECG results before and during mouse heart pacing. c, Strength-duration curve when pacing at 480 bpm. n = 3 biologically independent animals.
Extended Data Fig. 5 Selection of LEDs and optical filters for multi-site, time-synchronized cardiac pacing.
a, Emission spectra for LEDs 1 and 2. b, Transmission curves for filters 1 and 2. c, Transmitted light intensities as a function of incident intensities from LEDs 1 and (2) for filters 1 and 2.
Supplementary information
Supplementary Information
Supplementary Methods, Notes 1–11, Tables 1–3, Figs. 1–26 and References.
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Zhang, Y., Rytkin, E., Zeng, L. et al. Millimetre-scale bioresorbable optoelectronic systems for electrotherapy. Nature 640, 77–86 (2025). https://doi.org/10.1038/s41586-025-08726-4
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DOI: https://doi.org/10.1038/s41586-025-08726-4
