Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

A viscoelastic adhesive epicardial patch for treating myocardial infarction


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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.

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.


  1. 1.

    Rane, A. A. & Christman, K. L. Biomaterials for the treatment of myocardial infarction: a 5-year update. J. Am. Coll. Cardiol. 58, 2615–2629 (2011).

    CAS  Article  Google Scholar 

  2. 2.

    Laflamme, M. A. & Murry, C. E. Heart regeneration. Nature 473, 326–335 (2011).

    CAS  Article  Google Scholar 

  3. 3.

    Wei, K. et al. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature 525, 479–485 (2015).

    CAS  Article  Google Scholar 

  4. 4.

    Shadrin, I. Y. et al. Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues. Nat. Commun. 8, 1825 (2017).

    Article  Google Scholar 

  5. 5.

    Fujimoto, K. L. et al. An elastic, biodegradable cardiac patch induces contractile smooth muscle and improves cardiac remodeling and function in subacute myocardial infarction. J. Am. Coll. Cardiol. 49, 2292–2300 (2007).

    CAS  Article  Google Scholar 

  6. 6.

    Didie, M. et al. Parthenogenetic stem cells for tissue-engineered heart repair. J. Clin. Invest. 123, 1285–1298 (2013).

    CAS  Article  Google Scholar 

  7. 7.

    Liao, S.-Y. et al. Attenuation of left ventricular adverse remodeling with epicardial patching after myocardial infarction. J. Card. Fail. 16, 590–598 (2010).

    Article  Google Scholar 

  8. 8.

    Stuckey, D. J. et al. Magnetic resonance imaging evaluation of remodeling by cardiac elastomeric tissue scaffold biomaterials in a rat model of myocardial infarction. Tissue Eng. Part A 16, 3395–3402 (2010).

    CAS  Article  Google Scholar 

  9. 9.

    Fujimoto, K. L. et al. Placement of an elastic biodegradable cardiac patch on a subacute infarcted heart leads to cellularization with early developmental cardiomyocyte characteristics. J. Card. Fail. 18, 585–595 (2012).

    Article  Google Scholar 

  10. 10.

    Chi, N.-H., Yang, M.-C., Chung, T.-W., Chou, N.-K. & Wang, S.-S. Cardiac repair using chitosan-hyaluronan/silk fibroin patches in a rat heart model with myocardial infarction. Carbohydr. Polym. 92, 591–597 (2013).

    CAS  Article  Google Scholar 

  11. 11.

    Serpooshan, V. et al. The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction. Biomaterials 34, 9048–9055 (2013).

    CAS  Article  Google Scholar 

  12. 12.

    Vilaeti, A. D. et al. Short-term ventricular restraint attenuates post-infarction remodeling in rats. Int. J. Cardiol. 165, 278–284 (2013).

    Article  Google Scholar 

  13. 13.

    D’Amore, A. et al. Bi-layered polyurethane—extracellular matrix cardiac patch improves ischemic ventricular wall remodeling in a rat model. Biomaterials 107, 1–14 (2016).

    Article  Google Scholar 

  14. 14.

    Moainie, S. L. et al. Infarct restraint attenuates remodeling and reduces chronic ischemic mitral regurgitation after postero-lateral infarction. Ann. Thorac. Surg. 74, 444–449 (2002).

    Article  Google Scholar 

  15. 15.

    Fomovsky, G. M., Clark, S. A., Parker, K. M., Ailawadi, G. & Holmes, J. W. Anisotropic reinforcement of acute anteroapical infarcts improves pump function. Circ. Heart Fail. 5, 515–522 (2012).

    Article  Google Scholar 

  16. 16.

    Enomoto, Y. et al. Early ventricular restraint after myocardial infarction: extent of the wrap determines the outcome of remodeling. Ann. Thorac. Surg. 79, 881–887 (2005).

    Article  Google Scholar 

  17. 17.

    Clarke, S. A., Ghanta, R. K., Ailawadi, G. & Holmes, J. W. in Cardiovascular and Cardiac Therapeutic Devices (ed. Franz, T.) 169–206 (Springer Berlin Heidelberg, 2014).

  18. 18.

    Clarke, S. A., Goodman, N. C., Ailawadi, G. & Holmes, J. W. Effect of scar compaction on the therapeutic efficacy of anisotropic reinforcement following myocardial infarction in the dog. J. Cardiovasc. Transl. Res. 8, 353–361 (2015).

    Article  Google Scholar 

  19. 19.

    Piao, H. et al. Effects of cardiac patches engineered with bone marrow-derived mononuclear cells and PGCL scaffolds in a rat myocardial infarction model. Biomaterials 28, 641–649 (2007).

    CAS  Article  Google Scholar 

  20. 20.

    Sarig, U. et al. Natural myocardial ECM patch drives cardiac progenitor based restoration even after scarring. Acta Biomater. 44, 209–220 (2016).

    CAS  Article  Google Scholar 

  21. 21.

    Gu, X. et al. Sustained viral gene delivery from a micro-fibrous, elastomeric cardiac patch to the ischemic rat heart. Biomaterials 133, 132–143 (2017).

    CAS  Article  Google Scholar 

  22. 22.

    Mazza, E. & Ehret, A. E. Mechanical biocompatibility of highly deformable biomedical materials. J. Mech. Behav. Biomed. Mater. 48, 100–124 (2015).

    CAS  Article  Google Scholar 

  23. 23.

    Winter, H. H. & Chambon, F. Analysis of linear viscoelasticity of a crosslinking polymer at the gel point. J. Rheol. 30, 367–382 (1986).

    CAS  Article  Google Scholar 

  24. 24.

    Chambon, F. & Winter, H. H. Linear viscoelasticity at the gel point of a crosslinking PDMS with imbalanced stoichiometry. J. Rheol. 31, 683–697 (1987).

    CAS  Article  Google Scholar 

  25. 25.

    Zhang, Y. S. & Khademhosseini, A. Advances in engineering hydrogels. Science 356, eaaf3627 (2017).

    Article  Google Scholar 

  26. 26.

    Yuk, H., Zhang, T., Lin, S., Parada, G. A. & Zhao, X. Tough bonding of hydrogels to diverse non-porous surfaces. Nat. Mater. 15, 190–196 (2016).

    CAS  Article  Google Scholar 

  27. 27.

    Oz, M. C. et al. Global surgical experience with the acorn cardiac support device. J. Thorac. Cardiov. Sur. 126, 983–991 (2003).

    Article  Google Scholar 

  28. 28.

    Ghanta, R. K. et al. Adjustable, physiological ventricular restraint improves left ventricular mechanics and reduces dilatation in an ovine model of chronic heart failure. Circulation 115, 1201–1210 (2007).

    Article  Google Scholar 

  29. 29.

    Ende, N. Amylase activity in body fluids. Cancer 14, 1109–1114 (1961).

    CAS  Article  Google Scholar 

  30. 30.

    Omens, J. H., Mackenna, D. A. & Mcculloch, A. D. Measurement of strain and analysis of stress in resting rat left-ventricular myocardium. J. Biomech. 26, 665–676 (1993).

    CAS  Article  Google Scholar 

  31. 31.

    Lin, Y. D. et al. A nanopatterned cell-seeded cardiac patch prevents electro-uncoupling and improves the therapeutic efficacy of cardiac repair. Biomater. Sci. 2, 567–580 (2014).

    CAS  Article  Google Scholar 

  32. 32.

    Kutschka, I. et al. Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts. Circulation 114, I167–I173 (2006).

    PubMed  Google Scholar 

  33. 33.

    Simpson, D., Liu, H., Fan, T. H., Nerem, R. & Dudley, S. C. Jr. A tissue engineering approach to progenitor cell delivery results in significant cell engraftment and improved myocardial remodeling. Stem Cells 25, 2350–2357 (2007).

    Article  Google Scholar 

  34. 34.

    Liang, S. et al. Paintable and rapidly bondable conductive hydrogels as therapeutic cardiac patches. Adv. Mater. 30, e1704235 (2018).

    Article  Google Scholar 

  35. 35.

    Efraim, Y. et al. Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction. Acta Biomater. 50, 220–233 (2017).

    CAS  Article  Google Scholar 

  36. 36.

    Ravi, S. et al. Effect of bone marrow-derived extracellular matrix on cardiac function after ischemic injury. Biomaterials 33, 7736–7745 (2012).

    CAS  Article  Google Scholar 

  37. 37.

    Jin, J. et al. Transplantation of mesenchymal stem cells within a poly(lactide-co-ɛ-caprolactone) scaffold improves cardiac function in a rat myocardial infarction model. Eur. J. Heart Fail. 11, 147–153 (2009).

    CAS  Article  Google Scholar 

  38. 38.

    Giraud, M.-N. et al. Hydrogel-based engineered skeletal muscle grafts normalize heart function early after myocardial infarction. Artif. Organs 32, 692–700 (2008).

    CAS  Article  Google Scholar 

  39. 39.

    Siepe, M. et al. Myoblast-seeded biodegradable scaffolds to prevent post-myocardial infarction evolution toward heart failure. J. Thorac. Cardiovasc. Sur. 132, 124–131 (2006).

    Article  Google Scholar 

  40. 40.

    Hashizume, R. et al. The effect of polymer degradation time on functional outcomes of temporary elastic patch support in ischemic cardiomyopathy. Biomaterials 34, 7353–7363 (2013).

    CAS  Article  Google Scholar 

  41. 41.

    Mewhort, H. E. M. et al. Bioactive extracellular matrix scaffold promotes adaptive cardiac remodeling and repair. JACC Basic Transl. Sci. 2, 450–464 (2017).

    Article  Google Scholar 

  42. 42.

    Singelyn, J. M. et al. Catheter-deliverable hydrogel derived from decellularized ventricular extracellular matrix increases endogenous cardiomyocytes and preserves cardiac function post-myocardial infarction. J. Am. Coll. Cardiol. 59, 751–763 (2012).

    CAS  Article  Google Scholar 

  43. 43.

    Dai, W. et al. Intramyocardial injection of heart tissue-derived extracellular matrix improves postinfarction cardiac function in rats. J. Cardiovasc. Pharmacol. Ther. 18, 270–279 (2013).

    Article  Google Scholar 

  44. 44.

    Hassaballah, A. I., Hassan, M. A., Mardi, A. N. & Hamdi, M. An inverse finite element method for determining the tissue compressibility of human left ventricular wall during the cardiac cycle. PLoS ONE 8, e82703 (2013).

    Article  Google Scholar 

  45. 45.

    Wang, H. M. et al. Structure-based finite strain modelling of the human left ventricle in diastole. Int. J. Numer. Meth. Bio. 29, 83–103 (2013).

    Article  Google Scholar 

  46. 46.

    Eriksson, T. S. E., Prassl, A. J., Plank, G. & Holzapfel, G. A. Influence of myocardial fiber/sheet orientations on left ventricular mechanical contraction. Math. Mech. Solids 18, 592–606 (2013).

    Article  Google Scholar 

  47. 47.

    Gao, H., Carrick, D., Berry, C., Griffith, B. E. & Luo, X. Y. Dynamic finite-strain modelling of the human left ventricle in health and disease using an immersed boundary-finite element method. IMA J. Appl. Math. 79, 978–1010 (2014).

    Article  Google Scholar 

  48. 48.

    Hall, J. E. Guyton and Hall Textbook of Medical Physiology (Elsevier Health Sciences, 2015).

  49. 49.

    Mielniczuk, L. M. et al. Left ventricular end-diastolic pressure and risk of subsequent heart failure in patients following an acute myocardial infarction. Congest. Heart Fail. 13, 209–214 (2007).

    Article  Google Scholar 

  50. 50.

    Holzapfel, G. A. & Ogden, R. W. Constitutive modelling of passive myocardium: a structurally based framework for material characterization. Phil. Trans. R. Soc. A 367, 3445–3475 (2009).

    Article  Google Scholar 

  51. 51.

    Guccione, J. M. & Mcculloch, A. D. Mechanics of active contraction in cardiac-muscle. 1. Constitutive relations for fiber stress that describe deactivation. J. Biomech. Eng. Trans. ASME 115, 72–81 (1993).

    CAS  Article  Google Scholar 

  52. 52.

    Guccione, J. M., Waldman, L. K. & Mcculloch, A. D. Mechanics of active contraction in cardiac-muscle. 2. Cylindrical models of the systolic left-ventricle. J. Biomech. Eng. Trans. ASME 115, 82–90 (1993).

    CAS  Article  Google Scholar 

  53. 53.

    Rodriguez, E. K., Omens, J. H., Waldman, L. K. & Mcculloch, A. D. Effect of residual stress on transmural sarcomere length distributions in rat left ventricle. Am. J. Physiol. 264, H1048–H1056 (1993).

    CAS  PubMed  Google Scholar 

  54. 54.

    Walker, J. C. et al. Magnetic resonance imaging-based finite element stress analysis after linear repair of left ventricular aneurysm. J. Thorac. Cardiov. Sur. 135, 1094–1102 (2008).

    Article  Google Scholar 

  55. 55.

    Goktepe, S., Abilez, O. J. & Kuhl, E. A generic approach towards finite growth with examples of athlete’s heart, cardiac dilation, and cardiac wall thickening. J. Mech. Phys. Solids 58, 1661–1680 (2010).

    Article  Google Scholar 

  56. 56.

    Himpel, G., Kuhl, E., Menzel, A. & Steinmann, P. Computational modelling of isotropic multiplicative growth. CMES Comp. Model. Eng. Sci. 8, 119–134 (2005).

    Google Scholar 

  57. 57.

    Genet, M., Lee, L. C., Baillargeon, B., Guccione, J. M. & Kuhl, E. Modeling pathologies of diastolic and systolic heart failure. Ann. Biomed. Eng. 44, 112–127 (2016).

    CAS  Article  Google Scholar 

  58. 58.

    Puso, M. A. & Weiss, J. A. Finite element implementation of anisotropic quasi-linear viscoelasticity using a discrete spectrum approximation. J. Biomech. Eng. Trans. ASME 120, 62–70 (1998).

    CAS  Article  Google Scholar 

  59. 59.

    Maas, S. A., Ellis, B. J., Ateshian, G. A. & Weiss, J. A. FEBio: finite elements for biomechanics. J. Biomech. Eng. Trans. ASME 134, 011005 (2012).

    Article  Google Scholar 

  60. 60.

    Tsai, J. Z. et al. In-vivo measurement of swine myocardial resistivity. IEEE Trans. Biomed. Eng. 49, 472–483 (2002).

    Article  Google Scholar 

  61. 61.

    Gabriel, C., Peyman, A. & Grant, E. H. Electrical conductivity of tissue at frequencies below 1 MHz. Phys. Med. Biol. 54, 4863–4878 (2009).

    CAS  Article  Google Scholar 

  62. 62.

    Li, J. et al. Tough adhesives for diverse wet surfaces. Science 357, 378–381 (2017).

    CAS  Article  Google Scholar 

  63. 63.

    Mehdizadeh, M., Weng, H., Gyawali, D., Tang, L. P. & Yang, J. Injectable citrate-based mussel-inspired tissue bioadhesives with high wet strength for sutureless wound closure. Biomaterials 33, 7972–7983 (2012).

    CAS  Article  Google Scholar 

  64. 64.

    Guo, J. S. et al. Click chemistry improved wet adhesion strength of mussel-inspired citrate-based antimicrobial bioadhesives. Biomaterials 112, 275–286 (2017).

    CAS  Article  Google Scholar 

  65. 65.

    Jeon, E. Y. et al. Rapidly light-activated surgical protein glue inspired by mussel adhesion and insect structural crosslinking. Biomaterials 67, 11–19 (2015).

    CAS  Article  Google Scholar 

Download references


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




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 or Ning Sun or Huajian Gao.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Lin, X., Liu, Y., Bai, A. et al. A viscoelastic adhesive epicardial patch for treating myocardial infarction. Nat Biomed Eng 3, 632–643 (2019).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing