nature.com

Millimetre-scale bioresorbable optoelectronic systems for electrotherapy

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.

Access through your institution

Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

$29.99 / 30 days

cancel any time

Learn more

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Learn more

Buy this article

Purchase on SpringerLink

Instant access to full article PDF

Buy now

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Learn about institutional subscriptions

Read our FAQs

Contact customer support

Fig. 1: Design of injectable, self-powered, bioresorbable cardiac pacemakers with wireless, optoelectronic control.

Fig. 2: Optoelectronic characteristics and ex vivo pacing with human and porcine hearts.

Fig. 3: In vivo demonstration of pacemaker injection and closed-chest pacing in canine model.

Fig. 4: In vivo demonstration of multi-site, time-synchronized pacing in canine models.

Fig. 5: Design of a wireless, skin-interfaced optoelectronic system for closed-loop cardiac electrotherapy.

Fig. 6: Ex vivo demonstration of cardiac pacing with a collection of pacemakers integrated with a TAVR valve in a human heart.

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](https://www.nature.com/articles/s41586-025-08726-4#ref-CR49 "Millimetre-scale, bioresorbable optoelectronic systems for minimally invasive electrotherapy. Code Ocean

https://codeocean.com/capsule/9406347/tree/v1

(2025).")).

References

Choi, Y. S. et al. Fully implantable and bioresorbable cardiac pacemakers without leads or batteries. Nat. Biotechnol. 39, 1228–1238 (2021).

CASPubMedPubMed CentralMATHGoogle Scholar

Zhang, Y. et al. Advances in bioresorbable materials and electronics. Chem. Rev. 123, 11722–11773 (2023).

CASPubMedGoogle Scholar

Choi, Y. S. et al. A transient, closed-loop network of wireless, body-integrated devices for autonomous electrotherapy. Science 376, 1006–1012 (2022).

ADSCASPubMedPubMed CentralMATHGoogle Scholar

Lumia, F. J. & Rios, J. C. Temporary transvenous pacemaker therapy: an analysis of complications. Chest 64, 604–608 (1973).

CASPubMedMATHGoogle Scholar

Wood, M. A. & Ellenbogen, K. A. Cardiac pacemakers from the patient’s perspective. Circulation 105, 2136–2138 (2002).

PubMedMATHGoogle Scholar

Bar-Cohen, Y. et al. Minimally invasive implantation of a micropacemaker into the pericardial space. Circ. Arrhythm. Electrophysiol. 11, e006307 (2018).

PubMedPubMed CentralGoogle Scholar

Zhao, J. et al. Permanent epicardial pacing in neonates and infants less than 1 year old: 12-year experience at a single center. Transl. Pediatr. 11, 825–833 (2022).

PubMedPubMed CentralMATHGoogle Scholar

Wildbolz, M., Dave, H., Weber, R., Gass, M. & Balmer, C. Pacemaker implantation in neonates and infants: favorable outcomes with epicardial pacing systems. Pediatr. Cardiol. 41, 910–917 (2020).

PubMedGoogle Scholar

Wilhelm, M. J. et al. Cardiac pacemaker infection: surgical management with and without extracorporeal circulation. Ann. Thorac. Surg. 64, 1707–1712 (1997).

CASPubMedMATHGoogle Scholar

Donovan, K. D. & Lee, K. Y. Indications for and complications of temporary transvenous cardiac pacing. Anaesth. Intensive Care 13, 63–70 (1985).

CASPubMedGoogle Scholar

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).

ADSPubMedMATHGoogle Scholar

Ouyang, H. et al. Symbiotic cardiac pacemaker. Nat. Commun. 10, 1821 (2019).

ADSPubMedPubMed CentralMATHGoogle Scholar

Lyu, H. et al. Synchronized biventricular heart pacing in a closed-chest porcine model based on wirelessly powered leadless pacemakers. Sci. Rep. 10, 2067 (2020).

ADSCASPubMedPubMed CentralMATHGoogle Scholar

Ho, J. S. et al. Wireless power transfer to deep-tissue microimplants. Proc. Natl Acad. Sci. USA 111, 7974–7979 (2014).

ADSCASPubMedPubMed CentralMATHGoogle Scholar

Wang, S. et al. A self-assembled implantable microtubular pacemaker for wireless cardiac electrotherapy. Sci. Adv. 9, eadj0540 (2023).

CASPubMedPubMed CentralGoogle Scholar

Prominski, A. et al. Porosity-based heterojunctions enable leadless optoelectronic modulation of tissues. Nat. Mater. 21, 647–655 (2022).

ADSCASPubMedGoogle Scholar

Liu, Z. et al. Photoelectric cardiac pacing by flexible and degradable amorphous Si radial junction stimulators. Adv. Healthc. Mater. 9, 1901342 (2020).

CASGoogle Scholar

Wang, L. et al. A fully biodegradable and self-electrified device for neuroregenerative medicine. Sci. Adv. 6, eabc6686 (2020).

ADSCASPubMedPubMed CentralGoogle Scholar

Zhang, Y. et al. Self-powered, light-controlled, bioresorbable platforms for programmed drug delivery. Proc. Natl. Acad. Sci. USA 120, e2217734120 (2023).

Huang, I. et al. High performance dual-electrolyte magnesium–iodine batteries that can harmlessly resorb in the environment or in the body. Energy Environ. Sci. 15, 4095–4108 (2022).

CASMATHGoogle Scholar

Won, S. M. et al. Natural wax for transient electronics. Adv. Funct. Mater. 28, 1801819 (2018).

MATHGoogle Scholar

Choi, Y. S. et al. Biodegradable polyanhydrides as encapsulation layers for transient electronics. Adv. Funct. Mater. 30, 2000941 (2020).

CASGoogle Scholar

Song, G. Control of biodegradation of biocompatable magnesium alloys. Corros. Sci. 49, 1696–1701 (2007).

CASMATHGoogle Scholar

Schauer, A. et al. Biocompatibility and degradation behavior of molybdenum in an in vivo rat model. Materials 14, 7776 (2021).

ADSCASPubMedPubMed CentralMATHGoogle Scholar

Yin, L. et al. Dissolvable metals for transient electronics. Adv. Funct. Mater. 24, 645–658 (2014).

CASMATHGoogle Scholar

Yu, K. J. et al. Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex. Nat. Mater. 15, 782–791 (2016).

ADSCASPubMedPubMed CentralMATHGoogle Scholar

Kang, S.-K. et al. Bioresorbable silicon electronic sensors for the brain. Nature 530, 71–76 (2016).

ADSCASPubMedMATHGoogle Scholar

Li, G. et al. Flexible transient phototransistors by use of wafer‐compatible transferred silicon nanomembranes. Small 14, e1802985 (2018).

ADSPubMedGoogle Scholar

Li, G. et al. Silicon nanomembrane phototransistor flipped with multifunctional sensors toward smart digital dust. Sci. Adv. 6, eaaz6511 (2020).

ADSCASPubMedPubMed CentralGoogle Scholar

López Ayerbe, J. et al. Temporary pacemakers: current use and complications. Rev. Esp. Cardiol. Engl. Ed. 57, 1045–1052 (2004).

MATHGoogle Scholar

Yu, L., Nina-Paravecino, F., Kaeli, D. & Fang, Q. Scalable and massively parallel Monte Carlo photon transport simulations for heterogeneous computing platforms. J. Biomed. Opt. 23, 1 (2018).

PubMedGoogle Scholar

Fang, Q. & Boas, D. A. Monte Carlo simulation of photon migration in 3D turbid media accelerated by graphics processing units. Opt. Express 17, 20178 (2009).

ADSCASPubMedGoogle Scholar

Taroni, P., Pifferi, A., Torricelli, A., Comelli, D. & Cubeddu, R. In vivo absorption and scattering spectroscopy of biological tissues. Photochem. Photobiol. Sci. 2, 124–129 (2003).

CASPubMedMATHGoogle Scholar

Khan, R., Gul, B., Khan, S., Nisar, H. & Ahmad, I. Refractive index of biological tissues: review, measurement techniques, and applications. Photodiagnosis Photodyn. Ther. 33, 102192 (2021).

CASPubMedMATHGoogle Scholar

Green, M. A. & Keevers, M. J. Optical properties of intrinsic silicon at 300 K. Prog. Photovoltaics Res. Appl. 3, 189–192 (1995).

CASGoogle Scholar

Firbank, M., Hiraoka, M., Essenpreis, M. & Delpy, D. T. Measurement of the optical properties of the skull in the wavelength range 650–950 nm. Phys. Med. Biol. 38, 503–510 (1993).

CASPubMedGoogle Scholar

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).

PubMedMATHGoogle Scholar

Chen, R. et al. Deep brain optogenetics without intracranial surgery. Nat. Biotechnol. 39, 161–164 (2021).

CASPubMedMATHGoogle Scholar

Yin, R. T. et al. Open thoracic surgical implantation of cardiac pacemakers in rats. Nat. Protoc. 18, 374–395 (2023).

CASPubMedMATHGoogle Scholar

Yang, Q. et al. Photocurable bioresorbable adhesives as functional interfaces between flexible bioelectronic devices and soft biological tissues. Nat. Mater. 20, 1559–1570 (2021).

ADSCASPubMedPubMed CentralMATHGoogle Scholar

Shea, J. B. & Sweeney, M. O. Cardiac resynchronization therapy a patient’s guide. Circulation 108, e64–e66 (2003).

Connolly, S. J., Kerr, C., Gent, M. & Yusuf, S. Dual-chamber versus ventricular pacing. Circulation 94, 578–583 (1996).

CASPubMedGoogle Scholar

Rodés-Cabau, J., Muntané-Carol, G. & Philippon, F. Managing conduction disturbances after TAVR: toward a tailored strategy. JACC Cardiovasc. Interv. 14, 992–994 (2021).

PubMedMATHGoogle Scholar

Urena, M. & Rodés-Cabau, J. Conduction abnormalities: the true Achilles’ heel of transcatheter aortic valve replacement? JACC Cardiovasc. Interv. 9, 2217–2219 (2016).

PubMedGoogle Scholar

Pagnesi, M. et al. Incidence, predictors, and prognostic impact of new permanent pacemaker implantation after TAVR with self-expanding valves. JACC Cardiovasc. Interv. 16, 2004–2017 (2023).

PubMedMATHGoogle Scholar

Reiter, C. et al. Delayed total atrioventricular block after transcatheter aortic valve replacement assessed by implantable loop recorders. JACC Cardiovasc. Interv. 14, 2723–2732 (2021).

PubMedGoogle Scholar

Muntané-Carol, G. et al. Ambulatory electrocardiographic monitoring following minimalist transcatheter aortic valve replacement. JACC Cardiovasc. Interv. 14, 2711–2722 (2021).

PubMedGoogle Scholar

Krishnaswamy, A. et al. Feasibility and safety of same-day discharge following transfemoral transcatheter aortic valve replacement. JACC Cardiovasc. Interv. 15, 575–589 (2022).

PubMedMATHGoogle Scholar

Millimetre-scale, bioresorbable optoelectronic systems for minimally invasive electrotherapy. Code Oceanhttps://codeocean.com/capsule/9406347/tree/v1 (2025).

Download references

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).

Author information

Author notes

These authors contributed equally: Yamin Zhang, Eric Rytkin, Liangsong Zeng, Jong Uk Kim, Lichao Tang, Haohui Zhang

Authors and Affiliations

Center for Bio-Integrated Electronics, Northwestern University, Evanston, IL, USA

Yamin Zhang, Jong Uk Kim, Seung Gi Seo, Jianyu Gu, Tianyu Yang, Naijia Liu, Wei Ouyang & John A. Rogers

Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL, USA

Yamin Zhang, Liangsong Zeng, Jong Uk Kim, Kaiyu Zhao, Yue Wang, Li Ding, Xinyue Lu, Elena Aprea, Gengming Jiang, Seung Gi Seo, Jin Wang, Jianyu Gu, Fei Liu, Tianyu Yang, Naijia Liu, Yinsheng Lu, Claire Hoepfner, Alex Hou, Rachel Nolander, Wei Ouyang, Igor R. Efimov & John A. Rogers

Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, Singapore

Yamin Zhang & Lichao Tang

Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA

Eric Rytkin, Yue Wang, Anastasia Lantsova, Altynai Melisova, Alex Hou, Rachel Nolander, Igor R. Efimov & John A. Rogers

Department of Mechanical Engineering, Northwestern University, Evanston, IL, USA

Liangsong Zeng, Shupeng Li, Yonggang Huang & John A. Rogers

Department of Civil and Environmental Engineering, Northwestern University, Evanston, IL, USA

Haohui Zhang & Zengyao Lv

Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Aleksei Mikhailov, Anna Pfenniger, Andrey Ardashev, Rishi K. Arora & Igor R. Efimov

Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA

Kaiyu Zhao, Jiayang Liu, Fei Liu, Yat Fung Larry Li, Nathan S. Purwanto, Yinsheng Lu, John M. Torkelson & John A. Rogers

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Li Ding

The BioRobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant’Anna, Pisa, Italy

Elena Aprea

Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA

Tong Wang & John M. Torkelson

Alnylam Pharmaceuticals Inc, Cambridge, MA, USA

Keith Bailey

Center for Comparative Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Amy Burrell

Department of Electrical and Computer Engineering, Northwestern University, Evanston, IL, USA

Yue Ying

Department of Electrical and Computer Engineering, University of Wisconsin-Madison, Madison, WI, USA

Jiarui Gong & Zhenqiang Ma

Department of Electronic Engineering, Incheon National University, Incheon, Republic of Korea

Jinheon Jeong & Sung Hun Jin

Department of Chemical Engineering, Dankook University, Yongin, Republic of Korea

Junhwan Choi

Department of Applied Physical Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Wubin Bai

Thayer School of Engineering, Dartmouth College, Hanover, NH, USA

Wei Ouyang

The University of Chicago Medicine, University of Chicago, Chicago, IL, USA

Rishi K. Arora

Authors

Yamin Zhang

View author publications