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Bovine Pericardium of High Fibre Dispersion Has High Fatigue Life and Increased Collagen Content; Potentially an Untapped Source of Heart Valve Leaflet Tissue

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Abstract

Bioprosthetic heart valves (BHVs) are implanted in aortic valve stenosis patients to replace the native, dysfunctional valve. Yet, the long-term performance of the glutaraldehyde-fixed bovine pericardium (GLBP) leaflets is known to reduce device durability. The aim of this study was to investigate a type of commercial-grade GLBP which has been over-looked in the literature to date; that of high collagen fibre dispersion (HD). Under uniaxial cyclic loading conditions, it was observed that the fatigue behaviour of HD GLBP was substantially equivalent to GLBP in which the fibres are highly aligned along the loading direction. It was also found that HD GLBP had a statistically significant 9.5% higher collagen content when compared to GLBP with highly aligned collagen fibres. The variability in diseased BHV delivery sites results in unpredictable and complex loading patterns across leaflets in vivo. This study presents the possibility of a shift from the traditional choice of circumferentially aligned GLBP leaflets, to that of high fibre dispersion arrangements. Characterised by its high fatigue life and increased collagen content, in addition to multiple fibre orientations, GLBP of high fibre dispersion may provide better patient outcomes under the multi-directional loading to which BHV leaflets are subjected in vivo.

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Abbreviations

AS:

Aortic valve stenosis

BHV:

Bioprosthetic heart valve

GLBP:

Glutaraldehyde-fixed bovine pericardium

HA:

Highly aligned fibres

HD:

High fibre dispersion

PD:

Preferred fibre direction

SALS:

Small angle light scattering

SHG:

Second harmonic generation

TAVR:

Transcatheter aortic valve replacement

XD:

Cross fibre direction

References

  1. Abbasi, M., and A. N. Azadani. Leaflet stress and strain distributions following incomplete transcatheter aortic valve expansion. J. Biomech. 48:3663–3671, 2015.

    PubMed  Google Scholar 

  2. Bouten, C., A. Driessen-Mol, and F. P. T. Baaijens. In situ heart valve tissue engineering: simple devices, smart materials, complex knowledge. Expert Rev. Med. Devices 9:453–455, 2012.

    CAS  PubMed  Google Scholar 

  3. Butterfield, M., and J. Fisher. Fatigue analysis of clinical bioprosthetic heart valves manufactured using photooxidized bovine pericardium. J. Heart Valve Dis. 9:161–166; discussion 167, 2000.

  4. Caballero, A., F. Sulejmani, C. Martin, T. Pham, and W. Sun. Evaluation of transcatheter heart valve biomaterials: biomechanical characterization of bovine and porcine pericardium. J. Mech. Behav. Biomed. Mater. 75:486–494, 2017.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Choe, J. A., S. Jana, B. J. Tefft, R. S. Hennessy, J. Go, D. Morse, A. Lerman, and M. D. Young. Biomaterial characterization of off-the-shelf decellularized porcine pericardial tissue for use in prosthetic valvular applications. J. Tissue Eng. Regen. Med. 12:1608–1620, 2018.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Dalgliesh, A. J., M. Parvizi, C. Noble, and L. G. Griffiths. Effect of cyclic deformation on xenogeneic heart valve biomaterials. PLoS ONE 14(6):e0214656, 2019.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Driessen, N. J. B., C. V. C. Bouten, and F. P. T. Baaijens. Improved prediction of the collagen fiber architecture in the aortic heart valve. J. Biomech. Eng. 127:329, 2005.

    PubMed  Google Scholar 

  8. Engelmayr, G. C., D. K. Hildebrand, F. W. Sutherland, J. E. Mayer, and M. S. Sacks. A novel bioreactor for the dynamic flexural stimulation of tissue engineered heart valve biomaterials. Biomaterials 24:2523–2532, 2003.

    CAS  PubMed  Google Scholar 

  9. García Páez, J. M., E. Jorge, A. Rocha, M. Maestro, J. L. Castillo-Olivares, I. Millan, A. Carrera, A. Cordon, G. Tellez, and R. Burgos. Mechanical effects of increases in the load applied in uniaxial and biaxial tensile testing: Part I. Calf pericardium. J. Mater. Sci. Mater. Med. 13:381–388, 2002.

    PubMed  Google Scholar 

  10. Gaul, R. T., D. R. Nolan, and C. Lally. Collagen fibre characterisation in arterial tissue under load using SALS. J. Mech. Behav. Biomed. Mater. 75:359–368, 2017.

    CAS  PubMed  Google Scholar 

  11. Ghasemi, M., D. R. Nolan, and C. Lally. An investigation into the role of different constituents in damage accumulation in arterial tissue and constitutive model development. Biomech. Model. Mechanobiol. 2018. https://doi.org/10.1007/s10237-018-1054-3.

    Article  PubMed  Google Scholar 

  12. Grunkemeier, G. L., H.-H. Li, D. C. Naftel, A. Starr, and S. H. Rahimtoola. Current Problems in Cardiology, long-term performance of heart valve prostheses. Curr. Probl. Cardiol. 25:78–154, 2000.

    Google Scholar 

  13. Gunning, P. S., N. Saikrishnan, A. P. Yoganathan, and L. M. McNamara. Total ellipse of the heart valve: the impact of eccentric stent distortion on the regional dynamic deformation of pericardial tissue leaflets of a transcatheter aortic valve replacement. J. R. Soc. Interface 12:20150737, 2015.

    PubMed  PubMed Central  Google Scholar 

  14. Hart, J. D., G. Cacciola, P. J. Schreurs, and G. W. Peters. A three-dimensional analysis of a fibre-reinforced aortic valve prosthesis. J. Biomech. 31:629–638, 1998.

    PubMed  Google Scholar 

  15. International Standards Organisation. ISO 5840-3:2013 Cardiovascular Implants—Cardiac Valve Prostheses. Part 3: Heart Valve Substitutes Implanted by Transcatheter Techniques. International Standards Organisation, 2013.

  16. Iyengar, A. K. S., H. Sugimoto, D. B. Smith, and M. S. Sacks. Dynamic in vitro quantification of bioprosthetic heart valve leaflet motion using structured light projection. Ann. Biomed. Eng. 29:963–973, 2001.

    PubMed  Google Scholar 

  17. James, A. P. Heart rate monitoring using human speech spectral features. Hum. Centric Comput. Inf. Sci. 5:33, 2015.

    Google Scholar 

  18. Joyce, K., Y. Rochev, and S. Rahmani. Assessment of the uniaxial experimental parameters utilised for the mechanical testing of bovine pericardium. J. Mech. Behav. Biomed. Mater. 96:27–37, 2019.

    CAS  PubMed  Google Scholar 

  19. Krasny, W., C. Morin, H. Magoariec, and S. Avril. A comprehensive study of layer-specific morphological changes in the microstructure of carotid arteries under uniaxial load. Acta Biomater. 57:342–351, 2017.

    PubMed  Google Scholar 

  20. Lester, S. J., B. Heilbron, K. Gin, A. Dodek, and J. Jue. The natural history and rate of progression of aortic stenosis. Chest 113(4):1109–1114, 1998.

    CAS  PubMed  Google Scholar 

  21. Li, K., and W. Sun. Simulated thin pericardial bioprosthetic valve leaflet deformation under static pressure-only loading conditions: implications for percutaneous valves. Ann. Biomed. Eng. 38:2690–2701, 2010.

    PubMed  Google Scholar 

  22. Martin, C., and W. Sun. Simulation of long-term fatigue damage in bioprosthetic heart valves: effects of leaflet and stent elastic properties. Biomech. Model. Mechanobiol. 13:759–770, 2014.

    PubMed  Google Scholar 

  23. Mirnajafi, A., J. Raymer, M. J. Scott, and M. S. Sacks. The effects of collagen fiber orientation on the flexural properties of pericardial heterograft biomaterials. Biomaterials 26:795–804, 2005.

    CAS  PubMed  Google Scholar 

  24. Osnabrugge, R. L. J., D. Mylotte, S. J. Head, N. M. Van Mieghem, V. T. Nkomo, C. M. LeReun, A. J. J. C. Bogers, N. Piazza, and A. P. Kappetein. Aortic stenosis in the elderly. J. Am. Coll. Cardiol. 62:1002–1012, 2013.

    PubMed  Google Scholar 

  25. Padala, M., E. L. Sarin, P. Willis, V. Babaliaros, P. Block, R. A. Guyton, and V. H. Thourani. An engineering review of transcatheter aortic valve technologies. Cardiovasc. Eng. Technol. 1:77–87, 2010.

    Google Scholar 

  26. Pasquino, E., S. Pascale, M. Andreon, S. Rinaldi, F. Laborde, and M. Galloni. Bovine pericardium for heart valve bioprostheses: in vitro and in vivo characterization of new chemical treatments. J. Mater. Sci. Mater. Med. 5:850–854, 1994.

    CAS  Google Scholar 

  27. Rotman, O. M., M. Bianchi, R. P. Ghosh, B. Kovarovic, and D. Bluestein. Principles of TAVR valve design, modelling, and testing. Expert Rev. Med. Devices 15:771–791, 2018.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Sacks, M. S., and C. J. Chuong. Orthotropic mechanical properties of chemically treated bovine pericardium. Ann. Biomed. Eng. 26:892–902, 1998.

    CAS  PubMed  Google Scholar 

  29. Sacks, M. S., A. Mirnajafi, W. Sun, and P. Schmidt. Bioprosthetic heart valve heterograft biomaterials: structure, mechanical behavior and computational simulation. Expert Rev. Med. Devices 3:817–834, 2006.

    CAS  PubMed  Google Scholar 

  30. Sacks, M. S., and F. J. Schoen. Collagen fiber disruption occurs independent of calcification in clinically explanted bioprosthetic heart valves. J. Biomed. Mater. Res. 62:359–371, 2002.

    CAS  PubMed  Google Scholar 

  31. Sacks, M. S., D. B. Smith, and E. D. Hiester. A small angle light scattering device for planar connective tissue microstructural analysis. Ann. Biomed. Eng. 25:678–689, 1997.

    CAS  PubMed  Google Scholar 

  32. Sánchez-Arévalo, F. M., M. Farfán, D. Covarrubias, R. Zenit, and G. Pulos. The micromechanical behavior of lyophilized glutaraldehyde-treated bovine pericardium under uniaxial tension. J. Mech. Behav. Biomed. Mater. 3:640–646, 2010.

    PubMed  Google Scholar 

  33. Schoen, F. J. Evolving concepts of cardiac valve dynamics: the continuum of development, functional structure, pathobiology, and tissue engineering. Circulation 118(18):1864–1880, 2008.

    PubMed  Google Scholar 

  34. Schoen, F. J., J. Fernandez, L. Gonzalez-Lavin, and A. Cernaianu. Causes of failure and pathologic findings in surgically removed Ionescu-Shiley standard bovine pericardial heart valve bioprostheses: emphasis on progressive structural deterioration. Circulation 76:618–627, 1987.

    CAS  PubMed  Google Scholar 

  35. Schultz, C. J., A. Weustink, N. Piazza, A. Otten, N. Mollet, G. Krestin, R. J. Van Geuns, P. De Feyter, P. W. J. Serruys, and P. De Jaegere. Geometry and degree of apposition of the CoreValve ReValving System with multislice computed tomography after implantation in patients with aortic stenosis. 2009. https://doi.org/10.1016/j.jacc.2009.04.075.

  36. Sellaro, T. L., D. Hildebrand, Q. Lu, N. Vyavahare, M. Scott, and M. S. Sacks. Effects of collagen fiber orientation on the response of biologically derived soft tissue biomaterials to cyclic loading. J. Biomed. Mater. Res. A 80:194–205, 2007.

    PubMed  Google Scholar 

  37. Siddiqui, R. F., J. R. Abraham, and J. Butany. Bioprosthetic heart valves: modes of failure. Histopathology 55:135–144, 2009.

    PubMed  Google Scholar 

  38. Singhal, P., A. Luk, and J. Butany. Bioprosthetic heart valves: impact of implantation on biomaterials. ISRN Biomater. 2013:1–14, 2013.

    Google Scholar 

  39. Smuts, A. N., D. C. Blaine, C. Scheffer, H. Weich, A. F. Doubell, and K. H. Dellimore. Application of finite element analysis to the design of tissue leaflets for a percutaneous aortic valve. J. Mech. Behav. Biomed. Mater. 4:85–98, 2011.

    CAS  PubMed  Google Scholar 

  40. Sulejmani, F., A. Caballero, C. Martin, T. Pham, and W. Sun. Evaluation of transcatheter heart valve biomaterials: computational modeling using bovine and porcine pericardium. J. Mech. Behav. Biomed. Mater. 97:159–170, 2019.

    PubMed  PubMed Central  Google Scholar 

  41. Sun, W., A. Abad, and M. S. Sacks. Simulated bioprosthetic heart valve deformation under quasi-static loading. J. Biomech. Eng. 127:905, 2005.

    PubMed  Google Scholar 

  42. Sun, W., K. Li, and E. Sirois. Simulated elliptical bioprosthetic valve deformation: implications for asymmetric transcatheter valve deployment. J. Biomech. 43:3085–3090, 2010.

    PubMed  Google Scholar 

  43. Sun, W., M. Sacks, G. Fulchiero, J. Lovekamp, N. Vyavahare, and M. Scott. Response of heterograft heart valve biomaterials to moderate cyclic loading. J. Biomed. Mater. Res. 69A:658–669, 2004.

    CAS  Google Scholar 

  44. Tremblay, D., T. Zigras, R. Cartier, L. Leduc, J. Butany, R. Mongrain, and R. L. Leask. A comparison of mechanical properties of materials used in aortic arch reconstruction. Ann. Thorac. Surg. 88:1484–1491, 2009.

    PubMed  Google Scholar 

  45. Vesely, I., and D. Boughner. Analysis of the bending behaviour of porcine xenograft leaflets and of natural aortic valve material: bending stiffness, neutral axis and shear measurements. J. Biomech. 22:655–671, 1989.

    CAS  PubMed  Google Scholar 

  46. Wells, S. M., T. Sellaro, and M. S. Sacks. Cyclic loading response of bioprosthetic heart valves: effects of fixation stress state on the collagen fiber architecture. Biomaterials 26:2611–2619, 2005.

    CAS  PubMed  Google Scholar 

  47. Whelan, A., J. Duffy, R. T. Gaul, D. O. Reilly, D. R. Nolan, P. Gunning, and C. Lally. Collagen fibre orientation and dispersion govern ultimate tensile strength, stiffness and the fatigue performance of bovine pericardium. J. Mech. Behav. Biomed. Mater. 90:54–60, 2019.

    CAS  PubMed  Google Scholar 

  48. Zhang, W., and M. S. Sacks. Modeling the response of exogenously crosslinked tissue to cyclic loading: the effects of permanent set. J. Mech. Behav. Biomed. Mater. 75:336–350, 2017.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Zilla, P., J. Brink, P. Human, and D. Bezuidenhout. Prosthetic heart valves: catering for the few. Biomaterials 29:385–406, 2008.

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Brenton Cavanagh (Royal College of Surgeons, Ireland) for his assistance and expertise in conducting the SHG imaging in this study. This research is funded by the Irish Research Council and Boston Scientific Corporation (EBPPG/2016/353).

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Correspondence to Caitríona Lally.

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Associate Editor Debra T. Auguste oversaw the review of this article.

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Appendix

Appendix

See Fig. 6 and Tables 3 and 4.

Figure 6
figure 6

SALS analysis overlaid on full GLBP patch. Interrogation region labelling (ax) correspond to fibre architecture detailed in Table 4.

Table 3 Specimen parameters and cycles completed for uniaxial cyclic loading detailed in “Uniaxial Cyclic Loading” section.
Table 4 Mean collagen fibre angle and alignment values for interrogation regions on GLBP patch (n = 24).

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Whelan, A., Williams, E., Nolan, D.R. et al. Bovine Pericardium of High Fibre Dispersion Has High Fatigue Life and Increased Collagen Content; Potentially an Untapped Source of Heart Valve Leaflet Tissue. Ann Biomed Eng 49, 1022–1032 (2021). https://doi.org/10.1007/s10439-020-02644-4

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