Electrical bioadhesive interface for bioelectronics


Reliable functions of bioelectronic devices require conformal, stable and conductive interfaces with biological tissues. Integrating bioelectronic devices with tissues usually relies on physical attachment or surgical suturing; however, these methods face challenges such as non-conformal contact, unstable fixation, tissue damage, and/or scar formation. Here, we report an electrical bioadhesive (e-bioadhesive) interface, based on a thin layer of a graphene nanocomposite, that can provide rapid (adhesion formation within 5 s), robust (interfacial toughness >400 J m−2) and on-demand detachable integration of bioelectronic devices on diverse wet dynamic tissues. The electrical conductivity (>2.6 S m−1) of the e-bioadhesive interface further allows bidirectional bioelectronic communications. We demonstrate biocompatibility, applicability, mechanical and electrical stability, and recording and stimulation functionalities of the e-bioadhesive interface based on ex vivo porcine and in vivo rat models. These findings offer a promising strategy to improve tissue–device integration and enhance the performance of biointegrated electronic devices.

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Fig. 1: Design and mechanism of the e-bioadhesive interface.
Fig. 2: Mechanical properties of the e-bioadhesive interface.
Fig. 3: Electrical properties of the e-bioadhesive interface.
Fig. 4: In vitro and in vivo biocompatibility of the e-bioadhesive interface.
Fig. 5: In vivo recording and stimulation via the e-bioadhesive interface.

Data availability

All relevant data that support the findings of this study are available in the article and its supplementary files. Source data of plots are provided with this paper. Source data are provided with this paper.

Code availability

No custom code is used in this study.


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We thank C.S. Nabzdyk at Mayo Clinic for the insightful discussions and suggestions, R. Bronson at Harvard Medical School for the histological analyses and D. Yang at MIT for help with the charge injection capacity tests. This work is supported by Centers for Mechanical Engineering Research and Education at MIT and SUSTech (MechERE Centers at MIT and SUSTech), the Innovation Committee of Shenzhen Municipality (JCYJ20170817111714314, C.F.G.), the National Natural Science Foundation of China (numbers U1613204 and 51771089, C.F.G.), the Science Technology the Shenzhen Sci-Tech Fund (KYTDPT20181011104007, C.F.G.) and the Guangdong Innovative and Entrepreneurial Research Team Program (2016ZT06G587, C.F.G.). H.Y. acknowledges financial support from a Samsung Scholarship.

Author information




H.Y., J.D. and X.Z. conceived the idea. J.D., H.Y., C.F.G. and X.Z. designed the study. J.D. and H.Y. developed the materials and methods for the e-bioadhesive interface. J.D., H.Y., J.W. and X.C. designed and performed the in vitro and ex vivo experiments. H.Y., J.W., C.E.V., J.D. and E.T.R. designed the in vivo experiments. J.W., H.Y., C.E.V. and J.D. performed the in vivo experiments. J.D., H.Y., C.F.G. and X.Z. analysed the data and wrote the manuscript with input from all authors.

Corresponding authors

Correspondence to Chuan Fei Guo or Xuanhe Zhao.

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The authors declare no competing interests.

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Extended data

Extended Data Fig. 1 Rapid and robust adhesion of a device on wet tissue surface by the e-bioadhesive interface.

a, Overall process of applying a device with the e-bioadhesive interface to an ex vivo porcine heart. b, Robust integration of the device to the wet heart surface.

Extended Data Fig. 2 Amine coupling of the e-bioadhesive interface.

a, Schematic illustration of covalent coupling of fluorescein with the e-bioadhesive interface by reaction between NHS ester groups in the e-bioadhesive interface and the primary amine groups in 6-amino fluorescein. b, c, Fluorescence microscopic images of the e-bioadhesive interface with (b) and without (c) NHS ester. 3 independent experiments were conducted with similar results.

Extended Data Fig. 3 Surface amine functionalization of various device materials.

a, Schematic illustration for primary amine functionalization of silicon and PDMS. b, Schematic illustration for primary amine functionalization of gold. c, Schematic illustration for primary amine functionalization of polyimide. d, Schematic illustration for primary amine functionalization of polycarbonate.

Extended Data Fig. 4 Schematic illustrations for the overall application process and mechanism of the e-bioadhesive interface.

The e-bioadhesive interface is assembled with bioelectronic devices to endow the ability to adhere to and electrically communicate with wet tissue surfaces. Upon contact with the wet tissue surface, the e-bioadhesive interface quickly absorbs the interfacial water and dry the tissue surface. The carboxylic acid groups in the e-bioadhesive interface form temporary physical crosslinks by hydrogen bonds and/or electrostatic interactions. The NHS ester groups in the e-bioadhesive interface subsequently form covalent crosslinks with the primary amine groups on the tissue surface and provide stable long-term tissue-device integration.

Extended Data Fig. 5 On-demand detachment of the e-bioadhesive interface.

a, Schematic illustrations for on-demand detachment of the e-bioadhesive interface by the triggering solution. b, Schematic illustrations for chemistry of the on-demand cleaving of hydrogen bonds between the e-bioadhesive interface and the tissue surface. c, Schematic illustrations for the on-demand cleaving of covalent disulfide bonds between the e-bioadhesive interface and the tissue surface.

Extended Data Fig. 6 Evaluation of compressive narrowing of carotid artery and sciatic nerve by the e-bioadhesive interface.

a, Schematic illustrations of a measurement setup for the potential compressive narrowing of tissues by the e-bioadhesive interface. b, Outer diameter of bare carotid artery, carotid artery with the dry and fully swollen e-bioadhesive interfaces. c, Outer diameter of bare sciatic nerve, sciatic nerve with the dry and fully swollen e-bioadhesive interfaces. Values in b,c represent the mean and the standard deviation (n = 4 independent samples). Statistical significance and P values are determined by two-sided Student t-test; ns, not significant. Source data

Extended Data Fig. 7 Adhesion performance of device integration to wet tissues by physical attachment.

a, Interfacial toughness between various tissues and polyimide substrates adhered by the e-bioadhesive interface and physical attachment. b, Shear strength between various tissues and polyimide substrates adhered by the e-bioadhesive interface and physical attachment. Values in a, b represent the mean and the standard deviation (n = 3 independent samples). Statistical significance and P values are determined by two-sided Student t-test; *** p ≤ 0.001; **** p ≤ 0.0001. Source data

Extended Data Fig. 8 Immunohistochemistry analysis of CD3, CD68, Collagen-I, and α-SMA expression.

Representative immunohistochemistry images of CD3, CD68, Collagen-I, and α-SMA for gold electrode with and without the e-bioadhesive interface after rat subcutaneous implantation for 14 days, respectively. 5 independent experiments were conducted with similar results.

Extended Data Fig. 9 Stability of in vivo performance.

Conductivity, impedance, and interfacial toughness of two gold electrodes adhered by the e-bioadhesive interface after 1 day and 14 days of incubation in PBS, and 14 days of in vivo implantation in rat dorsal subcutaneous pockets. Values represent the mean and the standard deviation (n = 3 independent samples). Statistical significance and P values are determined by two-sided Student t-test; ns, not significant. Source data

Extended Data Table 1 Comparison of various types of bioelectronic devices for wet tissues and organs

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Deng, J., Yuk, H., Wu, J. et al. Electrical bioadhesive interface for bioelectronics. Nat. Mater. (2020). https://doi.org/10.1038/s41563-020-00814-2

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