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A viscoelastic adhesive epicardial patch for treating myocardial infarction

Nature Biomedical Engineering volume 3, pages 632–643 (2019)Cite this article

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Abstract

Acellular epicardial patches that treat myocardial infarction by increasing the mechanical integrity of damaged left ventricular tissues exhibit widely scattered therapeutic efficacy. Here, we introduce a viscoelastic adhesive patch, made of an ionically crosslinked transparent hydrogel, that accommodates the cyclic deformation of the myocardium and outperforms most existing acellular epicardial patches in reversing left ventricular remodelling and restoring heart function after both acute and subacute myocardial infarction in rats. The superior performance of the patch results from its relatively low dynamic modulus, designed at the so-called ‘gel point’ via finite-element simulations of left ventricular remodelling so as to balance the fluid and solid properties of the material.

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Fig. 1: Finite-element simulation model for the epicardial patch.
Fig. 2: GPAP for MI treatment.
Fig. 3: Biocompatibility and stability of the GPAP.
Fig. 4: The GPAP improved heart function and reduced pathological cardiac remodelling after acute MI.
Fig. 5: The GPAP reduced myocyte hypertrophy and improved left ventricular systolic and diastolic functions after acute MI.
Fig. 6: The GPAP improved heart function and reduced pathological cardiac remodelling after subacute MI.
Fig. 7: The GPAP reduced pathological cardiac remodelling after acute MI from transcriptome levels.

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Data availability

All data supporting the findings of this study are available within the paper and its Supplementary Information files. Source data for the figures are available from the corresponding authors upon reasonable request. The RNA sequence data have been deposited in the National Center for Biotechnology Information Sequence Read Archive, with accession code SRP187341.

Code availability

The FEBio code is available upon reasonable request.

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Acknowledgements

We thank Y. Guan, A. J. Clasky and Y. Mao for material fabrication and characterization assistance, G. A. Holzapfel for discussions on the modelling methods, Y. Zhao for artwork, J. Wu for assistance with haemodynamics measurements, and C. Liu and H. Chen for assistance with rat surgery and echocardiology measurements. This work has been supported by the National Natural Science Foundation of China (81622032 and 51672184 to L.Y., 31571527 to N.S. and 81501858 to X.L.), National Science Foundation (CMMI-1562904 to H.G.), Jiangsu Innovation and Entrepreneurship Program (to L.Y.), National Key R&D Program of China (2016YFC1000500 and 2016YFC1305100 to N.S., and 2014CB748600 to L.Y.), Science and Technology Commission of Shanghai Municipality (numbers 17XD1400300 and 17JC1400200 to N.S.) and Priority Academic Program Development of Jiangsu Higher Education Institutions (to L.Y.).

Author information

Author notes

  1. Lei Yang

    Present address: School of Materials Science and Engineering, Hebei University of Technology, Tianjin, China

  2. These authors contributed equally: Xiao Lin, Yue Liu, Aobing Bai, Huanhuan Cai.

Authors and Affiliations

  1. Orthopedic Institute, Department of Orthopedics, The First Affiliated Hospital, Soochow University, Suzhou, China

    Xiao Lin, Huilin Yang & Lei Yang

  2. School of Engineering, Brown University, Providence, RI, USA

    Yue Liu & Huajian Gao

  3. Department of Physiology and Pathophysiology, State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Aobing Bai, Huanhuan Cai, Wei Jiang, Xinhong Wang & Ning Sun

  4. School of Public Health, College of Medicine, Soochow University, Suzhou, China

    Yanjie Bai

  5. International Research Center for Translational Orthopaedics (IRCTO), Suzhou, China

    Huilin Yang & Lei Yang

  6. Institute of Integrative Medicine, Fudan University, Shanghai, China

    Ning Sun

  7. Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, Shanghai, China

    Ning Sun

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Contributions

L.Y., N.S. and H.G. conceived and designed the study, analysed the data and provided funding. X.L., Y.B. and H.Y. carried out preparation and characterization of the GPAP, in vitro evaluation and data analysis. Y.L. performed the simulation work. A.B., H.C., W.J. and X.W. carried out the GPAP experiments for MI in rats, transcriptomic study and data collection. All authors wrote the manuscript.

Corresponding authors

Correspondence to Lei Yang, Ning Sun or Huajian Gao.

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Supplementary information

Supplementary Information

Supplementary methods, discussion, figures, tables, references and video captions.

Reporting Summary

Supplementary Video 1

Stretching of GPAP with a tweezer.

Supplementary Video 2

Demonstration of patching GPAP onto a rat heart.

Supplementary Video 3

Injection of GPAP through a syringe needle with an inner diameter of 1.2 mm.

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Lin, X., Liu, Y., Bai, A. et al. A viscoelastic adhesive epicardial patch for treating myocardial infarction. Nat Biomed Eng 3, 632–643 (2019). https://doi.org/10.1038/s41551-019-0380-9

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