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Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

Abstract

In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

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Figure 1: Schematics of the microelectronic cardiac patch concept.
Figure 2: Freestanding electronic mesh device.
Figure 3: Controlled release of biomolecules from the electronic device.
Figure 4: Biomaterial–electronics hybrid.
Figure 5: Tissue organization and function within the 3D electronic scaffold.
Figure 6: Remote control over the microECP function.

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Acknowledgements

T.D. acknowledges support from European Research Council (ERC) Starting Grant 637943, the European Union FP7 programme (Marie Curie, CIG), an Alon Fellowship, the Slezak Foundation, and the Israeli Science Foundation (700/13). R.F. thanks the Marian Gertner Institute for Medical Nanosystems Fellowship. The work is part of the doctoral thesis of R.F. at Tel Aviv University. We would like to thank T. Yoetz and N. Noor for technical assistance.

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Contributions

R.F. and T.D. conceived the idea and designed the experiments. R.F. performed all experiments. L.E. assisted in microfabrication and characterization of the electronics. S.F. and A.S. performed cell culture work. M.M. and I.G. assisted in drug release experiments. Y.S.-D. analysed data. R.F. and T.D. wrote the manuscript. The study was directed by T.D.

Corresponding author

Correspondence to Tal Dvir.

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The authors declare no competing financial interests.

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Feiner, R., Engel, L., Fleischer, S. et al. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function. Nature Mater 15, 679–685 (2016). https://doi.org/10.1038/nmat4590

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