Skip to main content
Log in

Experimental and Computational Investigation of Altered Mechanical Properties in Myocardium after Hydrogel Injection

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

The material properties of myocardium are an important determinant of global left ventricular function. Myocardial infarction results in a series of maladaptive geometric alterations which lead to increased stress and risk of heart failure. In vivo studies have demonstrated that material injection can mitigate these changes. More importantly, the material properties of these injectates can be tuned to minimize wall thinning and ventricular dilation. The current investigation combines experimental data and finite element modeling to correlate how injectate mechanics and volume influence myocardial wall stress. Experimentally, mechanics were characterized with biaxial testing and injected hydrogel volumes were measured with magnetic resonance imaging. Injection of hyaluronic acid hydrogel increased the stiffness of the myocardium/hydrogel composite region in an anisotropic manner, significantly increasing the modulus in the longitudinal direction compared to control myocardium. Increased stiffness, in combination with increased volume from hydrogel injection, reduced the global average fiber stress by ~14% and the transmural average by ~26% in the simulations. Additionally, stiffening in an anisotropic manner enhanced the influence of hydrogel treatment in decreasing stress. Overall, this work provides insight on how injectable biomaterials can be used to attenuate wall stress and provides tools to further optimize material properties for therapeutic applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Avants, B. B., N. J. Tustison, J. Wu, P. A. Cook, and J. C. Gee. An open source multivariate framework for n-tissue segmentation with evaluation on public data. Neuroinformatics 9(4):381–400, 2011.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Burdick, J. A., C. Chung, X. Jia, M. A. Randolph, and R. Langer. Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks. Biomacromolecules 6(1):386–391, 2005.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Dang, A. B., J. M. Guccione, J. M. Mishell, P. Zhang, A. W. Wallace, R. C. Gorman, J. H. Gorman, III, and M. B. Ratcliffe. Akinetic myocardial infarcts must contain contracting myocytes: finite-element model study. Am. J. Physiol. Heart Circ. Physiol. 288(4):H1844–H1850, 2005.

    Article  CAS  PubMed  Google Scholar 

  4. Demer, L. L., and F. C. Yin. Passive biaxial mechanical properties of isolated canine myocardium. J. Physiol. 339:615–630, 1983.

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Dobaczewski, M., C. Gonzalez-Quesada, and N. G. Frangogiannis. The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction. J. Mol. Cell. Cardiol. 48(3):504–511, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Dvir, T., A. Kedem, E. Ruvinov, O. Levy, I. Freeman, N. Landa, R. Holbova, M. S. Feinberg, S. Dror, Y. Etzion, J. Leor, and S. Cohen. Prevascularization of cardiac patch on the omentum improves its therapeutic outcome. Proc. Natl. Acad. Sci. USA 106(35):14990–14995, 2009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Engelmayr, Jr., G. C., M. Cheng, C. J. Bettinger, J. T. Borenstein, R. Langer, and L. E. Freed. Accordion-like honeycombs for tissue engineering of cardiac anisotropy. Nat. Mater. 7(12):1003–1010, 2008.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Epstein, F. H., Z. Yang, W. D. Gilson, S. S. Berr, C. M. Kramer, and B. A. French. Mr tagging early after myocardial infarction in mice demonstrates contractile dysfunction in adjacent and remote regions. Magn. Reson. Med. 48(2):399–403, 2002.

    Article  PubMed  Google Scholar 

  9. Fomovsky, G. M., J. R. Macadangdang, G. Ailawadi, and J. W. Holmes. Model-based design of mechanical therapies for myocardial infarction. J. Cardiovasc. Transl. Res. 4(1):82–91, 2011.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Guccione, J. M., A. D. McCulloch, and L. K. Waldman. Passive material properties of intact ventricular myocardium determined from a cylindrical model. J. Biomech. Eng. 113(1):42–55, 1991.

    Article  CAS  PubMed  Google Scholar 

  11. Gupta, V., and K. J. Grande-Allen. Effects of static and cyclic loading in regulating extracellular matrix synthesis by cardiovascular cells. Cardiovasc. Res. 72(3):375–383, 2006.

    Article  CAS  PubMed  Google Scholar 

  12. Holmes, J. W., T. K. Borg, and J. W. Covell. Structure and mechanics of healing myocardial infarcts. Annu. Rev. Biomed. Eng. 7:223–253, 2005.

    Article  CAS  PubMed  Google Scholar 

  13. Ifkovits, J. L., E. Tous, M. Minakawa, M. Morita, J. D. Robb, K. J. Koomalsingh, J. H. Gorman, 3rd, R. C. Gorman, and J. A. Burdick. Injectable hydrogel properties influence infarct expansion and extent of postinfarction left ventricular remodeling in an ovine model. Proc. Natl. Acad. Sci. USA 107(25):11507–11512, 2010.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Jacobs, N. T., D. Cortes, S. E. Szczesny, E. J. Vresilovic, and D. M. Elliott. Effect of boundary conditions on stress-strain uniformity in biaxial tension of annulus fibrosus. Annual Meeting of the Orthopaedic Research Society, 2011.

  15. Kortsmit, J., N. H. Davies, R. Miller, J. R. Macadangdang, P. Zilla, and T. Franz. The effect of hydrogel injection on cardiac function and myocardial mechanics in a computational post-infarction model. Comput. Methods Biomech. Biomed. Eng. 16(11):1185–1195, 2012.

    Article  Google Scholar 

  16. Lee, A. A., and A. D. McCulloch. Multiaxial myocardial mechanics and extracellular matrix remodeling: mechanochemical regulation of cardiac fibroblast function. Adv. Exp. Med. Biol. 430:227–240, 1997.

    Article  CAS  PubMed  Google Scholar 

  17. Liao, S. Y., C. W. Siu, Y. Liu, Y. Zhang, W. S. Chan, E. X. Wu, Y. Wu, J. M. Nicholls, R. A. Li, M. E. Benser, S. P. Rosenberg, E. Park, C. P. Lau, and H. F. Tse. Attenuation of left ventricular adverse remodeling with epicardial patching after myocardial infarction. J. Card. Fail. 16(7):590–598, 2010.

    Article  PubMed  Google Scholar 

  18. Morita, M., C. E. Eckert, K. Matsuzaki, M. Noma, L. P. Ryan, J. A. Burdick, B. M. Jackson, J. H. Gorman, III, M. S. Sacks, and R. C. Gorman. Modification of infarct material properties limits adverse ventricular remodeling. Ann. Thorac. Surg. 92(2):617–624, 2011.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Nelson, D. M., Z. Ma, K. L. Fujimoto, R. Hashizume, and W. R. Wagner. Intra-myocardial biomaterial injection therapy in the treatment of heart failure: materials, outcomes and challenges. Acta Biomater. 7(1):1–15, 2011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. O’Connell, G. D., S. Sen, and D. M. Elliott. Human annulus fibrosus material properties from biaxial testing and constitutive modeling are altered with degeneration. Biomech. Model. Mechanobiol. 11(3–4):493–503, 2011.

    PubMed Central  PubMed  Google Scholar 

  21. Rappaport, D., D. Adam, P. Lysyansky, and S. Riesner. Assessment of myocardial regional strain and strain rate by tissue tracking in b-mode echocardiograms. Ultrasound Med. Biol. 32(8):1181–1192, 2006.

    Article  PubMed  Google Scholar 

  22. Sacks, M. Biaxial mechanical evaluation of planar and biological materials. J. Elast. 61:199–246, 2001.

    Article  Google Scholar 

  23. Sled, J. G., A. P. Zijdenbos, and A. C. Evans. A nonparametric method for automatic correction of intensity nonuniformity in mri data. IEEE Trans. Med. Imaging 17(1):87–97, 1998.

    Article  CAS  PubMed  Google Scholar 

  24. Szczesny, S. E., J. M. Peloquin, D. H. Cortes, J. A. Kadlowec, L. J. Soslowsky, and D. M. Elliott. Biaxial tensile testing and constitutive modeling of human supraspinatus tendon. J. Biomech. Eng. 134(2):021004, 2012.

    Article  PubMed  Google Scholar 

  25. Tous, E., J. L. Ifkovits, K. J. Koomalsingh, T. Shuto, T. Soeda, N. Kondo, J. H. Gorman, 3rd, R. C. Gorman, and J. A. Burdick. Influence of injectable hyaluronic acid hydrogel degradation behavior on infarction-induced ventricular remodeling. Biomacromolecules 12(11):4127–4135, 2011.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Tous, E., B. Purcell, J. L. Ifkovits, and J. A. Burdick. Injectable acellular hydrogels for cardiac repair. J. Cardiovasc. Transl. Res. 4(5):528–542, 2011.

    Article  PubMed  Google Scholar 

  27. Tustison, N. J., B. B. Avants, P. A. Cook, Y. Zheng, A. Egan, P. A. Yushkevich, and J. C. Gee. N4itk: improved n3 bias correction. IEEE Trans. Med. Imaging 29(6):1310–1320, 2010.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Vannier, M. W., R. L. Butterfield, D. Jordan, W. A. Murphy, R. G. Levitt, and M. Gado. Multispectral analysis of magnetic resonance images. Radiology 154(1):221–224, 1985.

    CAS  PubMed  Google Scholar 

  29. Walker, J. C., M. B. Ratcliffe, P. Zhang, A. W. Wallace, B. Fata, E. W. Hsu, D. Saloner, and J. M. Guccione. Mri-based finite-element analysis of left ventricular aneurysm. Am. J. Physiol. Heart Circ. Physiol. 289(2):H692–H700, 2005.

    Article  CAS  PubMed  Google Scholar 

  30. Wall, S. T., J. C. Walker, K. E. Healy, M. B. Ratcliffe, and J. M. Guccione. Theoretical impact of the injection of material into the myocardium: a finite element model simulation. Circulation 114(24):2627–2635, 2006.

    Article  PubMed  Google Scholar 

  31. Wenk, J. F., P. Eslami, Z. Zhang, C. Xu, E. Kuhl, J. H. Gorman, 3rd, J. D. Robb, M. B. Ratcliffe, R. C. Gorman, and J. M. Guccione. A novel method for quantifying the in vivo mechanical effect of material injected into a myocardial infarction. Ann. Thorac. Surg. 92(3):935–941, 2011.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Wenk, J. F., L. Ge, Z. Zhang, D. Mojsejenko, D. D. Potter, E. E. Tseng, J. M. Guccione, and M. B. Ratcliffe. Biventricular finite element modeling of the acorn corcap cardiac support device on a failing heart. Ann. Thorac. Surg. 95(6):2022–2027, 2013.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Wenk, J. F., S. T. Wall, R. C. Peterson, S. L. Helgerson, H. N. Sabbah, M. Burger, N. Stander, M. B. Ratcliffe, and J. M. Guccione. A method for automatically optimizing medical devices for treating heart failure: designing polymeric injection patterns. J. Biomech. Eng. 131(12):121011, 2009.

    Article  PubMed  Google Scholar 

  34. Yin, F. C., R. K. Strumpf, P. H. Chew, and S. L. Zeger. Quantification of the mechanical properties of noncontracting canine myocardium under simultaneous biaxial loading. J. Biomech. 20(6):577–589, 1987.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge Daniel Adler in assisting with the analysis of the MRI images. This work was supported by the National Institutes of Health (R01 HL111090, T32 HL007954).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Jason A. Burdick or Jonathan F. Wenk.

Additional information

Associate Editor Jennifer West oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kichula, E.T., Wang, H., Dorsey, S.M. et al. Experimental and Computational Investigation of Altered Mechanical Properties in Myocardium after Hydrogel Injection. Ann Biomed Eng 42, 1546–1556 (2014). https://doi.org/10.1007/s10439-013-0937-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-013-0937-9

Keywords

Navigation