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Wirelessly operated bioelectronic sutures for the monitoring of deep surgical wounds

Nature Biomedical Engineering volume 5, pages 1217–1227 (2021)Cite this article

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Abstract

Monitoring surgical wounds post-operatively is necessary to prevent infection, dehiscence and other complications. However, the monitoring of deep surgical sites is typically limited to indirect observations or to costly radiological investigations that often fail to detect complications before they become severe. Bioelectronic sensors could provide accurate and continuous monitoring from within the body, but the form factors of existing devices are not amenable to integration with sensitive wound tissues and to wireless data transmission. Here we show that multifilament surgical sutures functionalized with a conductive polymer and incorporating pledgets with capacitive sensors operated via radiofrequency identification can be used to monitor physicochemical states of deep surgical sites. We show in live pigs that the sutures can monitor wound integrity, gastric leakage and tissue micromotions, and in rodents that the healing outcomes are equivalent to those of medical-grade sutures. Battery-free wirelessly operated bioelectronic sutures may facilitate post-surgical monitoring in a wide range of interventions.

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Fig. 1: Wirelessly responsive sutures for monitoring deep surgical wounds.
Fig. 2: Suture functionalization and characterization.
Fig. 3: Wireless system design and performance.
Fig. 4: In vivo post-operative monitoring.
Fig. 5: Chronic wireless sensing and wound healing outcomes.

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Data availability

The main data supporting the findings of this study are available within the paper and its supplementary information. Source data for Fig. 5f,g are provided with this paper. Other raw and analysed datasets generated during the study are available for research purposes from the corresponding authors on reasonable request.

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Acknowledgements

We thank Z. Goh for assisting in the art in Fig. 1a; A. Bansal and H. Li for supporting the in vitro experiments; and Y. X. Guo for facilitating the dielectric measurements. J.S.H. acknowledges support from grants from the National Research Foundation Singapore (NRFF2017-07 and AISG-GC-2019-002), Ministry of Education Singapore (MOE2016-T3-1-004) and the Institute for Health Innovation and Technology. P.L.R.E. acknowledges funding provided by the Ministry of Education Singapore (R148000240114). Part of the work was performed at the National University of Singapore Medicine Confocal Microscopy Unit.

Author information

Author notes

  1. Sybil Obuobi

    Present address: Drug Transport and Delivery Research Group, Department of Pharmacy, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway

  2. These authors contributed equally: Viveka Kalidasan, Xin Yang, Ze Xiong.

Authors and Affiliations

  1. Department of Electrical and Computer Engineering, National University of Singapore, Singapore, Singapore

    Viveka Kalidasan, Xin Yang, Ze Xiong, Xi Tian, Selman A. Kurt, Zhipeng Li & John S. Ho

  2. Institute for Health Innovation and Technology, National University of Singapore, Singapore, Singapore

    Ze Xiong, Benjamin C. K. Tee & John S. Ho

  3. The N.1 Institute for Health, National University of Singapore, Singapore, Singapore

    Ze Xiong, Benjamin C. K. Tee & John S. Ho

  4. Cardiovascular Research Institute, National University Heart Centre, Singapore, Singapore

    Renee R. Li, Jiong-Wei Wang & Christopher J. Charles

  5. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Renee R. Li, Jiong-Wei Wang & Christopher J. Charles

  6. Department of Materials Science and Engineering, National University of Singapore, Singapore, Singapore

    Haicheng Yao, Hareesh Godaba, Xin Guan, Benjamin C. K. Tee & Jianyong Ouyang

  7. Department of Pharmacy, National University of Singapore, Singapore, Singapore

    Sybil Obuobi, Devika Mukherjee & Pui Lai Rachel Ee

  8. Faculty of Dentistry, National University of Singapore, Singapore, Singapore

    Priti Singh & Weiqiang Loke

  9. Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore

    Ravisankar Rajarethinam

  10. Department of Surgery, National University Hospital, Singapore, Singapore

    Choon Seng Chong

  11. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Jiong-Wei Wang

  12. Nanomedicine Translational Research Programme, Centre for NanoMedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Jiong-Wei Wang

  13. Christchurch Heart Institute, Department of Medicine, University of Otago, Christchurch, New Zealand

    Christopher J. Charles

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  1. Viveka Kalidasan
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Contributions

V.K., X.Y., Z.X. and J.S.H. designed and performed the research. R.R.L., J.-W.W. and C.J.C. performed the large-animal studies. H.Y., H.G. and B.C.K.T. performed the mechanical testing experiments. R.R. conducted the histopathological studies. S.O., P.S., D.M., P.L.R.E. and W.L. performed the in vitro experiments and contributed materials. X.G. and J.O. assisted in the design of the fabrication process and contributed materials. X.T., S.A.K. and Z.L. supported the design and characterization of the wireless system. C.S.C. contributed to the study design. V.K., Z.X. and J.S.H. wrote the paper with input from all the authors.

Corresponding authors

Correspondence to Viveka Kalidasan, Ze Xiong or John S. Ho.

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The authors declare no competing interests.

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Peer review information Nature Biomedical Engineering thanks Keat Ghee Ong, Sameer Sonkusale and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Extended data

Extended Data Fig. 1 Radio-frequency response of different stitches and varying suture conductivity.

a-c, Current distribution on (a) Lembert, (b) lock, and (c) Cushing stitches at the fundamental f0 and harmonic 2f0 frequencies. The stitches are excited by a plane wave. d, Simulated received power detected by the wireless system at the second harmonic for Cushing stitch with varying conductivity at distance d from the antenna.

Extended Data Fig. 2 Effect of tissue curvature and spacing between adjacent sutures.

a,b, Schematic of the experimental setup for in-plane bending (a) and out-of-plane bending (b). c,d, Resonant frequency and averaged power over the operational band (2.2–3.4 GHz) measured for varying in-plane (c) and out-of-plane (d) bending angles. Error bars show the mean ± s.d. (n = 3 samples). e,f, Schematic diagrams of the test setup for wireless interference of WiSe with different spacing in X direction (e) and Y direction (f). WiSe sutures are separately labelled as WiSe1 and WiSe2. g,h, Measured harmonic backscattering spectra with various spacing in X direction (g) and Y direction (h).

Extended Data Fig. 3 Effect of suture length.

a,d Schematic of the experimental setup for suture with double-side (a) or single-side (d) cutting. The suture is placed under 2.5 cm porcine tissue and the length of varied Lembert stitches. b,e Averaged received power and received harmonic power (at 2.4 GHz) of WiSe over the operation band with double-side (b) or single-side (e) cutting. Error bars show the mean ± s.d. (n = 3 samples). c,f Harmonic signal received (at 2.4 GHz) for sutures with length 0, 10, and 20 mm on each side (c) or left side (f) of the pledget.

Extended Data Fig. 4 WiSe suture breakage test.

a, Schematic of test setup for simulating suture breakage under 2.5 cm porcine tissue. b, Heatmap of the received harmonic signal power as a function of the length of the left segment of the suture L' and the angle θ of the unravelled segment. c, Corresponding measured harmonic signal at 2.4 GHz. The signals are normalized to the initial suture state (0 dB). The angle θ is used to vary the effective length of the dipole antenna formed by the suture. In clinical applications, the unravelled segment is expected to spontaneously bunch together due to agitation by natural body motions61, which also leads to reduction of the effective dipole antenna length.

Extended Data Fig. 5 in vivo post-operative monitoring in rat model.

a, Illustration of the rodent surgical wound model. WiSe sutures were used to close an incision on the gluteal muscle and the skin over the wound stitched with unmodified silk sutures. Leakage of gastric fluid is simulated by subcutaneous injection of artificial gastric solution and breakage of the suture by cutting near the center of the surgical stitch. b, Computed tomography image of the surgical site. Dashed lines show WiSe suture estimated from the position of electronic pledget. c-e, Frequency-resolved wireless readout of the WiSe suture during implantation (c), gastric leakage (d), and suture breakage (e). Signal amplitudes were separately normalized based on the minimum amplitude of each group. f-h, Time-resolved wireless readout of the WiSe suture during implantation (f), gastric leakage (g), and suture breakage (h). Lower panels show respiratory waveforms aligned and normalized to the peak. i-k, Spectrogram (continuous wavelet transform) of the time-resolved signal. Red arrows indicate spectral peaks corresponding to the respiratory rate (RR, 0.28 Hz) and its second and third harmonics.

Extended Data Fig. 6 Reader antenna positioning.

a, Illustration of the steps to position the reader antenna. b, Contour plot of the received harmonic signal power when the position of the antenna is scanned within a 40 mm × 40 mm area. c, Measured backscattering signal for the antenna positions in (b). Yellow shading indicates the 10 mm × 10 mm area with highest signal amplitude. d, Resonant frequency and received power as a function of the orientation angle of the antenna. Blue shading denotes the frequency uncertainty due to decrease in the signal-to-noise ratio. e, Harmonic backscattering spectra for varying orientation angles.

Extended Data Fig. 7 Chronic wireless sensing in vivo.

a, Time-resolved wireless readout of WiSe suture applied to muscle wound on day 1, day 14, after simulated gastric leakage on day 14, and after simulated suture breakage on day 14. b, Signal-to-noise ratio (SNR) of wireless readout from WiSe sutures applied to skin wounds on rats over 14 days. Sutures are naturally removed by the rats as the skin wound heals. Box plots show the mean, upper quartile, and lower quartile (n = 5 rats on day 1 and n = 1 rat on day 14). c, Backscattering signals from a WiSe suture applied to a muscle wound over 14 days. Dash line indicates the harmonic signal amplitude on day 1. d,e, Representative H&E-stained tissue sections from the skin and muscle wounds near the sutures. Solid black arrows show skin re-epithelization (d), dashed black arrows show wound closure in muscle (e). Scale bars, 500 μm.

Supplementary information

Supplementary Information

Supplementary notes, figures, tables, references and video captions.

Reporting Summary

Supplementary Video 1

Suturing technique by threading the electronic pledget.

Supplementary Video 2

Suturing technique by knotting the electronic pledget.

Supplementary Video 3

Real-time wireless response of a surgical stitch.

Supplementary Video 4

Frequency-resolved wireless readout of a deep surgical stitch.

Supplementary Video 5

Ultrasound imaging of a suture in a porcine model.

Source data

Source Data for Fig. 5

Source data for Fig. 5f,g.

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Kalidasan, V., Yang, X., Xiong, Z. et al. Wirelessly operated bioelectronic sutures for the monitoring of deep surgical wounds. Nat Biomed Eng 5, 1217–1227 (2021). https://doi.org/10.1038/s41551-021-00802-0

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