An epicardial bioelectronic patch is an important device for investigating and treating heart diseases. The ideal device should possess cardiac-tissue-like mechanical softness and deformability, and be able to perform spatiotemporal mapping of cardiac conduction characteristics and other physical parameters. However, existing patches constructed from rigid materials with structurally engineered mechanical stretchability still have a hard–soft interface with the epicardium, which can strain cardiac tissue and does not allow for deformation with a beating heart. Alternatively, patches made from intrinsically soft materials lack spatiotemporal mapping or sensing capabilities. Here, we report an epicardial bioelectronic patch that is made from materials matching the mechanical softness of heart tissue and can perform spatiotemporal mapping of electrophysiological activity, as well as strain and temperature sensing. Its capabilities are illustrated on a beating porcine heart. We also show that the patch can provide therapeutic capabilities (electrical pacing and thermal ablation), and that a rubbery mechanoelectrical transducer can harvest energy from heart beats, potentially providing a power source for epicardial devices.
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The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.
Custom code used to process the data is available from the corresponding author upon reasonable request.
Heron, M. & Anderson, R. N. Changes in the Leading Cause of Death: Recent Patterns in Heart Disease and Cancer Mortality Data Brief 254 (NCHS, 2016).
Mozaffarian, D. et al. Executive summary: Heart disease and stroke statistics—2016 update. Circulation 133, 447–454 (2016).
Mair, H., Jansens, J.-L., Lattouf, O. M., Reichart, B. & Dabritz, S. Epicardial lead implantation techniques for biventricular pacing via left lateral mini-thoracotomy, video-assisted thoracoscopy, and robotic approach. Heart Surg. Forum 6, 412–417 (2003).
Costa, R., Scanavacca, M., da Silva, K. R., Martinelli Filho, M. & Carrillo, R. Novel approach to epicardial pacemaker implantation in patients with limited venous access. Heart Rhythm 10, 1646–1652 (2013).
Boyle, N. G. & Shivkumar, K. Epicardial interventions in electrophysiology. Circulation 126, 1752–1769 (2012).
Cantwell, C. D. et al. Techniques for automated local activation time annotation and conduction velocity estimation in cardiac mapping. Comput. Biol. Med. 65, 229–242 (2015).
Dubois, R. et al. Non-invasive cardiac mapping in clinical practice: application to the ablation of cardiac arrhythmias. J. Electrocardiol. 48, 966–974 (2015).
Ershad, F., Sim, K., Thukral, A., Zhang, Y. S. & Yu, C. Invited article: emerging soft bioelectronics for cardiac health diagnosis and treatment. APL Mater. 7, 031301 (2018).
Erem, B., Brooks, D. H., van Dam, P. M., Stinstra, J. G. & MacLeod, R. S. Spatiotemporal estimation of activation times of fractionated ECGs on complex heart surfaces. In 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society 5884-5887 (IEEE, 2011).
Gu, S. et al. Mapping conduction velocity of early embryonic hearts with a robust fitting algorithm. Biomed. Opt. Express 6, 2138–2157 (2015).
Fang, H. et al. Capacitively coupled arrays of multiplexed flexible silicon transistors for long-term cardiac electrophysiology. Nat. Biomed. Eng. 1, 0038 (2017).
Viventi, J. et al. A conformal, bio-interfaced class of silicon electronics for mapping cardiac electrophysiology. Sci. Transl. Med. 2, 24ra22 (2010).
Kim, D. H. et al. Electronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy. Proc. Natl Acad. Sci. USA 109, 19910–19915 (2012).
Xu, L. et al. 3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium. Nat. Commun. 5, 3329 (2014).
Xu, L. et al. Materials and fractal designs for 3D multifunctional integumentary membranes with capabilities in cardiac electrotherapy. Adv. Mater. 27, 1731–1737 (2015).
Lee, W. et al. Nonthrombogenic, stretchable, active multielectrode array for electroanatomical mapping. Sci. Adv. 4, eaau2426 (2018).
Blakney, A. K., Swartzlander, M. D. & Bryant, S. J. The effects of substrate stiffness on the in vitro activation of macrophages and in vivo host response to poly(ethylene glycol)‐based hydrogels. J. Biomed. Mater. Res. A 100, 1375–1386 (2012).
Engler, A. J. et al. Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: scar-like rigidity inhibits beating. J. Cell Sci. 121, 3794–3802 (2008).
Kim, D. H. et al. Epidermal electronics. Science 333, 838–843 (2011).
Park, J. et al. Electromechanical cardioplasty using a wrapped elasto-conductive epicardial mesh. Sci. Transl. Med. 8, 344ra386 (2016).
Davenport Huyer, L. et al. Highly elastic and moldable polyester biomaterial for cardiac tissue engineering applications. ACS Biomater. Sci. Eng. 2, 780–788 (2016).
Kapnisi, M. et al. Auxetic cardiac patches with tunable mechanical and conductive properties toward treating myocardial infarction. Adv. Funct. Mater. 28, 1800618 (2018).
Reis, L. A., Chiu, L. L. Y., Feric, N., Fu, L. & Radisic, M. Biomaterials in myocardial tissue engineering. J. Tissue Eng. Regen. Med. 10, 11–28 (2016).
Sim, K. et al. Fully rubbery integrated electronics from high effective mobility intrinsically stretchable semiconductors. Sci. Adv. 5, eaav5749 (2019).
Kim, H.-J., Thukral, A., Sharma, S. & Yu, C. Biaxially stretchable fully elastic transistors based on rubbery semiconductor nanocomposites. Adv. Mater. Technol. 3, 1800043 (2018).
Kim, H.-J., Sim, K., Thukral, A. & Yu, C. Rubbery electronics and sensors from intrinsically stretchable elastomeric composites of semiconductors and conductors. Sci. Adv. 3, e1701114 (2017).
Lee, H. et al. Highly stretchable and transparent supercapacitor by Ag–Au core–shell nanowire network with high electrochemical stability. ACS Appl. Mater. Interfaces 8, 15449–15458 (2016).
Momtahan, N. et al. Automation of pressure control improves whole porcine heart decellularization. Tissue Eng. C 21, 1148–1161 (2015).
Ji, Y. et al. High-performance p-type copper(i) thiocyanate thin film transistors processed from solution at low temperature. Adv. Mater. Interfaces 6, 1900883 (2019).
Lenz, J., del Giudice, F., Geisenhof, F. R., Winterer, F. & Weitz, R. T. Vertical, electrolyte-gated organic transistors show continuous operation in the mA cm−2 regime and artificial synaptic behaviour. Nat. Nanotechnol. 14, 579–585 (2019).
Kim, S. H., Hong, K., Lee, K. H. & Frisbie, C. D. Performance and stability of aerosol-jet-printed electrolyte-gated transistors based on poly(3-hexylthiophene). ACS Appl. Mater. Interfaces 5, 6580–6585 (2013).
Xu, J. et al. Highly stretchable polymer semiconductor films through the nanoconfinement effect. Science 355, 59 (2017).
Xu, J. et al. Multi-scale ordering in highly stretchable polymer semiconducting films. Nat. Mater. 18, 594–601 (2019).
Oh, J. Y. et al. Stretchable self-healable semiconducting polymer film for active-matrix strain-sensing array. Sci. Adv. 5, eaav3097 (2019).
Wang, S. et al. Skin electronics from scalable fabrication of an intrinsically stretchable transistor array. Nature 555, 83 (2018).
Nguyen, J. S., Lakkis, N. M., Bobek, J., Goswami, R. & Dokainish, H. Systolic and diastolic myocardial mechanics in patients with cardiac disease and preserved ejection fraction: impact of left ventricular filling pressure. J. Am. Soc. Echocardiogr. 23, 1273–1280 (2010).
Howard-Quijano, K. et al. Left ventricular endocardial and epicardial strain changes with apical myocardial ischemia in an open-chest porcine model. Physiol. Rep. 4, e13042 (2016).
D’Hooge, J. et al. Regional strain and strain rate measurements by cardiac ultrasound: principles, implementation and limitations. Eur. J. Echocardiogr. 1, 154–170 (2000).
Ferraiuoli, P. et al. Full-field analysis of epicardial strain in an in vitro porcine heart platform. J. Mech. Behav. Biomed. Mater. 91, 294–300 (2019).
Fenton, F. H., Gizzi, A., Cherubini, C., Pomella, N. & Filippi, S. Role of temperature on nonlinear cardiac dynamics. Phys. Rev. E 87, 042717 (2013).
Lim, H. S. et al. Noninvasive mapping to guide atrial fibrillation ablation. Card. Electrophysiol. Clin. 7, 89–98 (2015).
Narayan, S. M. et al. Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (conventional ablation for atrial fibrillation with or without focal impulse and rotor modulation) trial. J. Am. Coll. Cardiol. 60, 628–636 (2012).
Diederich, C. J. Thermal ablation and high-temperature thermal therapy: overview of technology and clinical implementation. Int. J. Hyperth. 21, 745–753 (2005).
Webb, H., Lubner, M. G. & Hinshaw, J. L. Thermal ablation. Semin. Roentgenol. 46, 133–141 (2011).
Toprak, A. & Tigli, O. Piezoelectric energy harvesting: state-of-the-art and challenges. Appl. Phys. Rev. 1, 031104 (2014).
Wu, C., Wang, A. C., Ding, W., Guo, H. & Wang, Z. L. Triboelectric nanogenerator: a foundation of the energy for the new era. Adv. Energy Mater. 9, 1802906 (2019).
Zhang, C. & Wang, Z. L. in Micro Electro Mechanical Systems (ed. Huang, Q.-A.) 1335–1376 (Springer, 2018).
Sánchez-Quintana, D., Doblado-Calatrava, M., Cabrera, J. A., Macías, Y. & Saremi, F. Anatomical basis for the cardiac interventional electrophysiologist. Biomed Res. Int. 2015, 547364 (2015).
Tang, A. S. L. et al. Cardiac-resynchronization therapy for mild-to-moderate heart failure. N. Engl. J. Med. 363, 2385–2395 (2010).
Jayaprakash, S. Clinical presentations, diagnosis, and management of arrhythmias associated with cardiac tumors. J. Arrhythm. 34, 384–393 (2018).
Cheng, L. K. et al. Detailed measurements of gastric electrical activity and their implications on inverse solutions. In 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society 1302–1305 (IEEE, 2009).
Ballaro, A., Mundy, A. R., Fry, C. H. & Craggs, M. D. Bladder electrical activity: the elusive electromyogram. BJU Int. 92, 78–84 (2003).
Thukral, A., Ershad, F., Enan, N., Rao, Z. & Yu, C. Soft ultrathin silicon electronics for soft neural interfaces: a review of recent advances of soft neural interfaces based on ultrathin silicon. IEEE Nanotechnol. Mag. 12, 21–34 (2018).
Baba, T. et al. Early neuropsychological dysfunction in elderly high-risk patients after on-pump and off-pump coronary bypass surgery. J. Anesth. 21, 452–458 (2007).
Zhang, H., Iijima, K., Huang, J., Walcott, G. P. & Rogers, J. M. Optical mapping of membrane potential and epicardial deformation in beating hearts. Biophys. J. 111, 438–451 (2016).
Dandel, M., Lehmkuhl, H., Knosalla, C., Suramelashvili, N. & Hetzer, R. Strain and strain rate imaging by echocardiography—basic concepts and clinical applicability. Curr. Cardiol. Rev. 5, 133–148 (2009).
Aletras, A. H., Balaban, R. S. & Wen, H. High-resolution strain analysis of the human heart with fast-DENSE. J. Magn. Reson. 140, 41–57 (1999).
Guill, A. et al. QT interval heterogeneities induced through local epicardial warming/cooling. An experimental study. Rev. Esp. Cardiol. (Engl. Ed.) 67, 993–998 (2014).
Kassiri, Z. et al. Combination of tumor necrosis factor-α ablation and matrix metalloproteinase inhibition prevents heart failure after pressure overload in tissue inhibitor of metalloproteinase-3 knock-out mice. Circ. Res. 97, 380–390 (2005).
Skonieczki, B. D., Wells, C., Wasser, E. J. & Dupuy, D. E. Radiofrequency and microwave tumor ablation in patients with implanted cardiac devices: is it safe? Eur. J. Radiol. 79, 343–346 (2011).
Oh, J. Y. et al. Self-seeded growth of poly(3-hexylthiophene) (P3HT) nanofibrils by a cycle of cooling and heating in solutions. Macromolecules 45, 7504–7513 (2012).
C.Y. would like to acknowledge the support by the National Science Foundation CAREER grant (CMMI-1554499), the Office of Naval Research grant (N00014-18-1-2338) under the Young Investigator Program, the National Institutes of Health grant (R21EB026175) and 3M non-tenured faculty award. F.E. acknowledges the National Science Foundation Graduate Research Fellowship Program.
The authors declare no competing interests.
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Sim, K., Ershad, F., Zhang, Y. et al. An epicardial bioelectronic patch made from soft rubbery materials and capable of spatiotemporal mapping of electrophysiological activity. Nat Electron 3, 775–784 (2020). https://doi.org/10.1038/s41928-020-00493-6
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