Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Accelerated intestinal wound healing via dual electrostimulation from a soft and biodegradable electronic bandage

Abstract

Intestinal wound healing is a long-standing problem, with conventional suturing-based intestinal closure surgeries typically leading to postoperative problems. Alternative strategies or devices capable of effective wound healing have thus been sought. Here we report a self-powered electronic bandage made from soft and biodegradable materials that can accelerate wound healing in the intestine. The device uses dual electrostimulation to promote wound healing: a pulsed electrostimulation that induces electrotransfection of epithelial cells, promoting the expression of healing factors (such as epithelial growth factor); and a d.c. electrostimulation that enhances secretion of healing factors of the transfected cells. The electronic bandage exhibits high transfection efficiency and cell viability for intestinal epithelial cells in vitro, which boosts epithelial growth factor expression during the intraoperative period. Its self-powered galvanic cell from a magnesium and molybdenum microelectrode pair promotes healing factor exocytosis. In vitro and in vivo studies in mice show accelerated intestinal would healing compared to conventional suture-based treatments and an electronic bandage with single electrostimulation.

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

Access options

Buy this article

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

Fig. 1: Fully implantable, biodegradable, self-powered dual-electrostimulation E-bandage for intestinal wound healing.
Fig. 2: The dual-electrostimulation E-bandage for in vitro ET and/or ES.
Fig. 3: In vitro study of the mechanisms of EGF expression and secretion promoted by the dual electrostimulation of the E-bandage.
Fig. 4: E-bandage for targeted gene ET and ES of wounded intestine in vivo.
Fig. 5: The therapeutic effect of the dual-electrostimulation E-bandage in promoting intestinal wound healing.
Fig. 6: Histological and functional assessments of the intestine healed through E-bandage treatment.

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding authors on reasonable request. Source data are provided with this paper.

References

  1. Schluter, J. et al. The gut microbiota is associated with immune cell dynamics in humans. Nature 588, 303–307 (2020).

    Article  Google Scholar 

  2. Jain, U. et al. Debaryomyces is enriched in Crohn’s disease intestinal tissue and impairs healing in mice. Science 371, 1154–1159 (2021).

    Article  Google Scholar 

  3. David, N. N., Aneel, B., Michael, K. & Douglas, M. B. Stapled versus handsewn intestinal anastomosis in emergency laparotomy: a systemic review and meta-analysis. Surgery 157, 609–618 (2015).

    Article  Google Scholar 

  4. Ho, Y. H. & Ashour, M. A. T. Techniques for colorectal anastomosis. World J. Gastroenterol. 16, 1610–1621 (2010).

    Article  Google Scholar 

  5. Slieker, J. C. et al. Systematic review of the technique of colorectal anastomosis. JAMA Surg. 148, 190–201 (2013).

    Article  Google Scholar 

  6. McElrath, C. et al. Critical role of interferons in gastrointestinal injury repair. Nat. Commun. 12, 2624–2639 (2021).

    Article  Google Scholar 

  7. Wu, J. et al. An off-the-shelf bioadhesive patch for sutureless repair of gastrointestinal defects. Sci. Transl. Med. 14, eabh2857 (2022).

    Article  Google Scholar 

  8. Yuk, H., Zhang, T., Lin, S., Parada, G. A. & Zhao, X. Tough bonding of hydrogels to diverse non-porous surfaces. Nat. Mater. 15, 190–196 (2016).

    Article  Google Scholar 

  9. Batalov, I., Stevens, K. R. & DeForest, C. A. Photopatterned biomolecule immobilization to guide three-dimensional cell fate in natural protein-based hydrogels. Proc. Natl Acad. Sci. USA 118, e2014194118 (2021).

    Article  Google Scholar 

  10. Jaroentomeechai, T. et al. Single-pot glycoprotein biosynthesis using a cell-free transcription-translation system enriched with glycosylation machinery. Nat. Commun. 9, 2686 (2018).

    Article  Google Scholar 

  11. Martino, M. M. et al. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science 343, 885–888 (2014).

    Article  Google Scholar 

  12. Yang, Y. et al. Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation. Nat. Commun. 13, 6908 (2022).

    Article  Google Scholar 

  13. Shine, A. & Abell, T. L. Role of gastric electrical stimulation in the treatment of gastroparesis. Gastrointest. Disord. 2, 12–26 (2020).

    Article  Google Scholar 

  14. Gutruf, P. et al. Fully implantable optoelectronic systems for battery-free, multimodal operation in neuroscience research. Nat. Electron. 1, 652–660 (2018).

    Article  Google Scholar 

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

    Article  Google Scholar 

  16. Jimbo, H. & Miki, N. Gastric-fluid-utilizing micro battery for micro medical devices. Sens. Actuators B Chem. 134, 219–224 (2008).

    Article  Google Scholar 

  17. Nadeau, P. et al. Prolonged energy harvesting for ingestible devices. Nat. Biomed. Eng. 1, 0022 (2017).

    Article  Google Scholar 

  18. Mostafalu, P. & Sonkusale, S. Flexible and transparent gastric battery: energy harvesting from gastric acid for endoscopy application. Biosens. Bioelectron. 54, 292–296 (2014).

    Article  Google Scholar 

  19. Tsang, M. et al. Biodegradable magnesium/iron batteries with polycaprolactone encapsulation: a microfabricated power source for transient implantable devices. Microsyst. Nanoeng. 1, 15024–15023 (2015).

    Article  Google Scholar 

  20. Kim, Y. J. et al. Biologically derived melanin electrodes in aqueous sodium-ion energy storage devices. Proc. Natl Acad. Sci. USA 110, 20912–20917 (2013).

    Article  Google Scholar 

  21. Yin, L. et al. Materials, designs, and operational characteristics for fully biodegradable primary batteries. Adv. Mater. 26, 3879–3784 (2014).

    Article  Google Scholar 

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

    Article  Google Scholar 

  23. Hamedi, H. et al. Chitosan based bioadhesives for biomedical applications: a review. Carbohydr. Polym. 282, 119100–119111 (2022).

    Article  Google Scholar 

  24. Mati-Baouche, N. et al. Chitosan as an adhesive. Eur. Polym. J. 60, 192–212 (2014).

    Article  Google Scholar 

  25. Ren, Z. et al. Rapid self-healing and self-adhesive chitosan-based hydrogels by host-guest interaction and dynamic covalent bond as flexible sensor. Carbohydr. Polym. 273, 118533–118544 (2021).

    Article  Google Scholar 

  26. Suo, H. et al. Interpenetrating polymer network hydrogels composed of chitosan and photocrosslinkable gelatin with enhanced mechanical properties for tissue engineering. Mater. Sci. Eng. C. 92, 612–620 (2018).

    Article  Google Scholar 

  27. Yuk, H. et al. Skin-inspired hydrogel-elastomer hybrids with robust interfaces and functional microstructures. Nat. Commun. 7, 12028–12038 (2016).

    Article  Google Scholar 

  28. Yuk, H., Wu, J. & Zhao, X. Hydrogel interfaces for merging humans and machines. Nat. Rev. Mater. 7, 935–952 (2022).

    Article  Google Scholar 

  29. Healy, K. E. & Ducheyne, P. The mechanisms of passive dissolution of titanium in a model physiological environment. J. Biomed. Mater. Res. 26, 319–338 (1992).

    Article  Google Scholar 

  30. Hussain, H. et al. Structure of a model TiO2 photocatalytic interface. Nat. Mater. 16, 461–466 (2017).

    Article  Google Scholar 

  31. Choi, J. J. E. et al. Mechanical properties of human oral mucosa tissues are site dependent: a combined biomechanical, histological and ultrastructural approach. Clin. Exp. Dent. Res. 6, 602–611 (2020).

    Article  Google Scholar 

  32. Liu, J., Qu, S., Suo, Z. & Yang, W. Functional hydrogel coatings. Natl Sci. Rev. 8, nwaa254 (2021).

    Article  Google Scholar 

  33. Mann, G. E., Sumitomo, T., Cáceres, C. H. & Griffiths, J. R. Reversible plastic strain during cyclic loading-unloading of Mg and Mg-Zn alloys. Mater. Sci. Eng. A 456, 138–146 (2007).

    Article  Google Scholar 

  34. Chen, X. et al. Achieving ultra-high ductility and fracture toughness in molybdenum via Mo2TiC2 MXene addition. Mater. Sci. Eng. A 818, 141422 (2021).

    Article  Google Scholar 

  35. Gallego-Perez, D. et al. Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue. Nat. Nanotechnol. 12, 974–979 (2017).

    Article  Google Scholar 

  36. Pang, S., Gao, Y. & Choi, S. Flexible and stretchable biobatteries: monolithic integration of membrane-free microbial fuel cells in a single textile layer. Adv. Energy Mater. 8, 1702261 (2018).

    Article  Google Scholar 

  37. Zhao, X. et al. Photocrosslinkable gelatin hydrogel for epidermal tissue engineering. Adv. Healthc. Mater. 5, 108–118 (2016).

    Article  Google Scholar 

  38. Leppik, L., Oliveira, K. M. C., Bhavsar, M. B. & Barker, J. H. Electrical stimulation in bone tissue engineering treatments. Eur. J. Trauma Emerg. S. 46, 231–244 (2020).

    Article  Google Scholar 

  39. Sigismund, S., Lanzetti, L., Scita, G. & Di Fiore, P. P. Endocytosis in the context-dependent regulation of individual and collective cell properties. Nat. Rev. Mol. Cell Biol. 22, 625–643 (2021).

    Article  Google Scholar 

  40. Cheng, L. & Hill, A. F. Therapeutically harnessing extracellular vesicles. Nat. Rev. Drug Discov. 21, 379–399 (2022).

    Article  Google Scholar 

  41. Starling, S. Probing α-cell dysfunction in type 2 diabetes mellitus. Nat. Rev. Endocrinol. 18, 195 (2022).

    Article  Google Scholar 

  42. Racioppi, L. et al. CaMKK2 in myeloid cells is a key regulator of the immune-suppressive microenvironment in breast cancer. Nat. Commun. 10, 2450 (2019).

    Article  Google Scholar 

  43. Stewart, L. M. et al. CaMKK2 facilitates golgi-associated vesicle trafficking to sustain cancer cell proliferation. Cell Death Dis. 12, 1040 (2021).

    Article  Google Scholar 

  44. 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).

    Article  Google Scholar 

  45. Rickard, J. et al. Surgical infections in low- and middle-income countries: a global assessment of the burden and management needs. Surg. Infect. 21, 478–494 (2020).

    Article  Google Scholar 

  46. Sommer, F., Anderson, J. M., Bharti, R., Raes, J. & Rosenstiel, P. The resilience of the intestinal microbiota influences health and disease. Nat. Rev. Microbiol. 15, 630–638 (2017).

    Article  Google Scholar 

  47. Yao, G. et al. A self-powered implantable and bioresorbable electrostimulation device for biofeedback bone fracture healing. Proc. Natl Acad. Sci. USA 118, e2100772118 (2021).

    Article  Google Scholar 

  48. Song, J. W. et al. Bioresorbable, wireless, and battery-free system for electrotherapy and impedance sensing at wound sites. Sci. Adv. 9, eade4687 (2023).

    Article  Google Scholar 

  49. Huang, Y. et al. Implantable electronic medicine enabled by bioresorbable microneedles for wireless electrotherapy and drug delivery. Nano Lett. 22, 5944–5953 (2022).

    Article  Google Scholar 

  50. Jiang, Y. et al. Wireless, closed-loop, smart bandage with integrated sensors and stimulators for advanced wound care and accelerated healing. Nat. Biotechnol. 41, 652–662 (2023).

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by National Key Research and Development Program of China (grant nos. 2022YFB3205600 and 2023YFC2415900), National Natural Science Foundation of China (grant nos. 32071407, 62003023), Beijing Natural Science Foundation (grant no. 7212204) (all to L.C.); and National Natural Science Foundation of China (grant no. 32101088) and Beijing Nova Program (grant nos. Z2111000021211133, 20220484225) (all to L.W.). We acknowledge critical support and infrastructure provided for this work by the Feng Chen. Zhejiang University of Technology, School of Materials Science and Engineering, and we thank M. Li, M. Yang and Ms. L. Du for their assistance.

Author information

Authors and Affiliations

Authors

Contributions

L.C., C.Y., L.W. and Y.F. supervised the project. L.C., H.L., H.W., Yuqiong Wang and L.W. designed the E-bandage (ET) system and experiment. H.W. conducted the in vitro experiments. Yuqiong Wang discovered the role of Ca2+ influx in EVs secretion. Yuqiong Wang and Y.H. conducted the in vivo mice experiments. H.W., H.L., Yuqiong Wang, X.J., Youdi Liu, X.Y., L.W., C.Y. and L.C. prepared the manuscript. H.W., H.L., Yi Wang, T.C. and L.C. processed the data and drew the figures. H.Z. and Z.Y. assisted in fabricating the E-bandage. H.S., F.L., S.D., Z.W., A.X., Z.D., M.L. and D.Y. assisted in the in vitro experiments. S.W., J.C., T.C., K.Y., Yilin Liu and S.K. assisted in the in vivo experiments. L.L., S.K. and Y. Li assisted in simulation. All authors discussed and agreed with the final version.

Corresponding authors

Correspondence to Liu Wang, Cunjiang Yu or Lingqian Chang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Electronics thanks Quansan Yang, Zhou Li and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Note 1, Figs. 1–31, Tables 1–6, Videos 1–3 and References.

Reporting Summary

Supplementary Video 1

The E-bandage in shaking and swing scenarios remained firmly adhered to the intestinal tissue.

Supplementary Video 2

E-bandage attached to the swelling surface of the intestine remained intact.

Supplementary Video 3

Ultrasound image after E-bandage implantation in mouse intestine.

Supplementary Data 1

Source data for Supplementary Figs. 2, 4, 5, 7–9, 11–17, 20–24, 27, 29 and 31.

Source data

Source Data Figs. 2–6

Statistical source data from Figs. 2–6 and unprocessed western blots from Figs. 2 and 3.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, H., Wang, Y., Li, H. et al. Accelerated intestinal wound healing via dual electrostimulation from a soft and biodegradable electronic bandage. Nat Electron 7, 299–312 (2024). https://doi.org/10.1038/s41928-024-01138-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41928-024-01138-8

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing