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Photocurable bioresorbable adhesives as functional interfaces between flexible bioelectronic devices and soft biological tissues


Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic–tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans.

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Fig. 1: Soft interface materials for joining bioelectronic devices with biological tissues.
Fig. 2: Key characteristics of the BTIM.
Fig. 3: Soft adhesive interfaces between wireless optoelectronics and dorsal subcutaneous tissues.
Fig. 4: Securing optical devices onto the brain and forming adhesive conduits for interconnects.
Fig. 5: Soft adhesive interfaces between wireless cardiac pacemakers and the myocardium.
Fig. 6: Ultrathin, flexible MEAs adhered to the epicardium.

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Data availability

Source data are provided with this paper. All other data that support the results in this study are available from the corresponding author upon reasonable request.

Code availability

Software for the analysis of optical mapping data, RHYTHM, is openly available for free download at Other custom codes used in this study are available from the corresponding author upon reasonable request.


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This work was generously funded by the Leducq Foundation project RHYTHM and the National Institutes of Health (R01-HL141470 to I.R.E. and J.A.R.). This work made use of the NUFAB facility of Northwestern University’s NUANCE Center, which received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633); the MRSEC programme (NSF DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; the Querrey Simpson Institute for Bioelectronics; the Keck Biophysics Facility, a shared resource of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, which received support in part by the NCI Cancer Center Support (P30 CA060553); the Center for Advanced Molecular Imaging (RRID:SCR_021192); Northwestern University; and the State of Illinois, through the IIN. R.T.Y. acknowledges support from the American Heart Association (19PRE34380781). M.W. acknowledges support from the National Institutes of Health (T32 AG20506). Z.X. acknowledges support from the National Natural Science Foundation of China (12072057), LiaoNing Revitalization Talents Program (XLYC2007196) and Fundamental Research Funds for the Central Universities (DUT20RC(3)032). K.A. acknowledges support from the National Institutes of Health (5K99-HL148523-02). Y.H. acknowledges support from the National Foundation of Science (CMMI1635443). Y.K. acknowledges support from the National Institutes of Health (R01NS107539 and R01MH117111), Beckman Young Investigator Award, Rita Allen Foundation Scholar Award and Searle Scholar Award. The diagrams of the mouse body with organs in Fig. 1f were created with

Author information

Authors and Affiliations



Q.Y., T. Wei, Y.K., I.R.E. and J.A.R. conceived the ideas and designed the research. Q.Y., T. Wei, Y.X. and T.-L.L. synthesized and characterized the materials. Q.Y., Y.X., J.K., Y.S.C., W.B., Y.Y., M.H., Q.Z., T. Wang, M.-H.S., H.L., S.M.L. and A. Banks designed and fabricated the devices. R.T.Y., M.W., S.W.C., I.K., S.Y., C.R.H., K.B.L., K.A., A. Brikha, I.S., F.A., E.A.W. and G.D.T. performed the in vitro, ex vivo and in vivo studies. Q.Y., R.T.Y., Y.X., M.W., C.R.H., A. Banks and E.A.W. performed the data analysis. Z.X., R.A. and Y.D. performed the mechanical and electrical modelling. Q.Y., Y.X., R.T.Y., T.W., M.W, J.M.T., Y.H., Y.K., I.R.E. and J.A.R. wrote the manuscript with input from all authors.

Corresponding authors

Correspondence to Yevgenia Kozorovitskiy, Igor R. Efimov or John A. Rogers.

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The authors declare no competing interests.

Additional information

Peer review information Nature Materials thanks John Ho, Yuhan Lee, Tsuyoshi Sekitani 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 Supporting matrices for electrode-embedded 3D electronic systems.

a, Schematic illustration of procedures to integrate 3D electronics into a matrix of the BTIM. The matrix allows manual manipulation without damaging fragile features, with the ability to bond to dynamic, curved tissue surfaces. b, Image of a 3D device formed by compressive buckling on an elastomer substrate. c, Micrograph of a 3D device in a BTIM supporting matrix. d, Schematic illustrations of the 2D precursor before compressive buckling (first panel) and the 3D structure after compressive buckling (second panel), with the measuring electrode in the central area. e, Schematic illustration of the original and deformed status of the non-encapsulated (first row) and the BTIM-encapsulated (second row) 3D devices under compressive pressure. f, g, Curves for impedance and phase angle over the frequency sweep without the BTIM before and after compressive pressure. h, i, Impedance and phase angle over the frequency sweep with the BTIM under static compression fatigue tests. j, k, Impedance and phase angle over the frequency sweep with the BTIM under dynamic compression fatigue tests (pressure: 2 kPa; cycle number: 104).

Source data

Extended Data Fig. 2 Influence of APTES-functionalization on bioelectronics surfaces.

a, ToF-SIMS analysis of a representative pristine bioelectronic surface (PLA). b, Steps for selective functionalization of this surface through a patterned polyimide adhesive-coated shadow mask. c, ToF-SIMS analysis on the shadowed area of the surface shows results that are similar to those from the pristine surface. d, ToF-SIMS analysis of the exposed area of the bioelectronic surface. To normalize the intensity, the intensity I28, where the mass is 28, was set as 100 and calculate the relative intensity of each case. e, Thickness of an APTES layer formed on a silicon wafer exposed in air and submerged in water as a function of time after formation. Spectroscopic ellipsometry was used for these measurements. f, Impedance of MEA electrodes at 1 kHz in 0.1 M PBS at room temperature before APTES functionalization and immediately and 7 days after APTES functionalization (F(2,123) = 0.0201, P = 0. 9801). n = 6 independent samples in e and n = 40 independent electrodes from 10 independent devices and 3 independent batches in f. Values in e and f represent the mean ± s.d. Statistical significance and P values are determined by one-way ANOVA at a significance level of 0.05. ns indicates no statistically significant differences.

Source data

Extended Data Fig. 3 Analysis of the electrical distributions associated with electrical stimulation.

a, Influence of the conductivity of the interface material on electrical stimulation. b, Current density distributions in the myocardium layer and the interface material with different conductivities. c, Potential distribution in the myocardium layer and the interface material with different conductivities. d, Corresponding potential distributions on the top of the myocardium layer as a function of the interface material conductivity. e, Ratio of the potential difference on the tissues (V3 – V4) to the corresponding potential difference on the electrodes (V1 – V2, 3 V) as a function of the interface material conductivity.

Source data

Extended Data Fig. 4 Analysis of the electrical distributions associated with biopotential mapping.

a, Influence of the conductivity of the BTIM on biopotential mapping. b, Biopotential distribution in the myocardium layer and the interface material layer with various conductivities. c, Calculated potential at all of the electrodes for different conductivities. d, Calculated potential on all the electrodes in the presence of the interface material layer with various conductivities (blue solid line) and in the absence of the interface material layer (red dash line).

Source data

Extended Data Fig. 5 Mechanical stability of BTIM-encapsulated wireless optoelectronics.

a, Original device position determined by photographs, and positions of BTIM-encapsulated devices (first row) and non-adhesive (second row) devices on day 1 (white), 4 (blue), and 7 (purple) post-surgery determined by MicroCT. b, c, Statistical analyses of the net translations (b) and rotations (c) of the µ-ILED in the BTIM-encapsulated (blue) and non-adhesive devices (red) on day 4 and 7 compared with those on day 1 post-surgery. n = 3 biologically independent animals. Values in b–c represent the mean ± s.d.

Source data

Extended Data Fig. 6 Applying BTIM on brain-integrated bioelectronics/optoelectronics.

a, Image of the brain areas exposed to the BTIM. b, c, Astrocyte area percentages and microglia area percentages for the sham group and the BTIM group. Black dots: animal average. Black dots: animal average, 4 animals in total. Grey dots: individual ROIs. 10–12 ROIs from 4 animals in total, 2–3 ROIs from each animal. P = 0.3546 in b and P = 0.8049 in c. d, The image of the BTIM-encapsulated b-MEA on a mouse brain ex vivo. e, Robust adhesion even when the b-MEA is lifted or shaken. n = 12 independent measurements from 4 biologically independent animals in b–c. Values in b–c represent the mean ± s.d. Statistical significance and P values are determined by two-sided Student’s t-test at a significance level of 0.05. ns indicates no statistically significant differences.

Source data

Extended Data Fig. 7 Electrogram signals of ventricular fibrillation from an MEA with BTIM encapsulation.

a, Representative electrogram signal collected from a Langendorff-perfused rabbit heart during ventricular fibrillation (VF). b, c, Phase (b) and voltage (c) map of VF over 2500 ms.

Source data

Supplementary information

Supplementary Information

Supplementary Notes 1–11, Tables 1 and 2 and Figs. 1–33.

Reporting Summary

Supplementary Video 1

Optoelectronic device remains in the bonded location and exhibits stable operation during natural movements of animals. The device can be wirelessly activated to emit red light (peak wavelength 630 nm), designed for its relevance in tumour irradiation.

Supplementary Video 2

BTIM firmly secures an optoelectronic device to the dorsal subcutaneous area throughout 2 months after surgery. The BTIM severs as an encapsulating coating in this situation.

Supplementary Video 3

Optoelectronic device encapsulated by the BTIM remains functional for 2 months after surgery.

Supplementary Video 4

Instability of the device coil on the mouse skull without the BTIM.

Supplementary Video 5

Stability of the device coil on the mouse skull with the BTIM encapsulating coating.

Supplementary Video 6

Battery-free devices designed for optogenetics remain functional for 2 weeks after surgery. The BTIM serves as an encapsulating coating in this situation.

Supplementary Video 7

Robust adhesion of the BTIM to a mouse cerebrum.

Supplementary Video 8

Adhesive conduit supports and protects an interconnect/cable under compression in vivo.

Supplementary Video 9

BTIM in the encapsulation strategy establishes conformal contact between electrodes of wireless cardiac pacemakers and the myocardium in vivo.

Supplementary Video 10

In vivo characterization of adhesion between electrodes and the epicardium. The heart can be dragged out of the chest due to the robust adhesion provided by the BTIM.

Supplementary Video 11

Characterization of adhesion between electrodes and the epicardium on day 10 after surgery. The robust adhesion remains in vivo 10 d after surgery.

Supplementary Video 12

In vivo representative ECG traces during rapid ventricular pacing at ~1,000 bpm.

Supplementary Video 13

Accurate mapping of ventricular fibrillation on a Langendorff-perfused rabbit heart. The BTIM serves as the interfacial layer in this situation to bridge the MEA and the myocardium.

Source data

Source Data Fig. 2

Raw data and statistical source data for Fig. 2.

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Source Data Extended Data Fig. 1

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

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