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Acute In Vivo Functional Assessment of a Biodegradable Stentless Elastomeric Tricuspid Valve

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Abstract

Degradable heart valves based on in situ tissue regeneration have been proposed as potentially durable and non-thrombogenic prosthetic alternatives. We evaluated the acute in vivo function, microstructure, mechanics, and thromboresistance of a stentless biodegradable tissue-engineered heart valve (TEHV) in the tricuspid position. Biomimetic stentless tricuspid valves were fabricated with poly(carbonate urethane)urea (PCUU) by double-component deposition (DCD) processing to mimic native valve mechanics and geometry. Five swine then underwent 24-h TEHV implantation in the tricuspid position. Echocardiography demonstrated good leaflet motion and no prolapse and trace to mild regurgitation in all but one animal. Histology revealed patches of proteinaceous deposits with no cellular uptake. SEM demonstrated retained scaffold microarchitecture with proteinaceous deposits but no platelet aggregation or thrombosis. Explanted PCUU leaflet thickness and mechanical anisotropy were comparable with native tricuspid leaflets. Bioinspired, elastomeric, stentless TEHVs fabricated by DCD were readily implantable and demonstrated good acute function in the tricuspid position.

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Abbreviations

DCD:

Double-component deposition

EE:

Epicardial echocardiography

PCUU:

Poly(carbonate urethane)urea

SEM:

Scanning electron micrography

TEHV:

Tissue-engineered heart valve

References

  1. 1.

    Delling, F. N., & Vasan, R. S. (2014). Epidemiology and pathophysiology of mitral valve prolapse: new insights into disease progression, genetics, and molecular basis. Circulation, 129, 2158–2170.

  2. 2.

    Neidenbach, R., Niwa, K., Oto, O., et al. (2018). Improving medical care and prevention in adults with congenital heart disease-reflections on a global problem-part I: development of congenital cardiology, epidemiology, clinical aspects, heart failure, cardiac arrhythmia. Cardiovascular Diagnosis and Therapy, 8, 705–715.

  3. 3.

    Iung, B., & Vahanian, A. (2011). Epidemiology of valvular heart disease in the adult. Nature Reviews. Cardiology, 8, 162–172.

  4. 4.

    Hoffman, J. I. E., & Kaplan, S. (2002). The incidence of congenital heart disease. Journal of the American College of Cardiology, 39, 1890–1900.

  5. 5.

    Grunkemeier, G. L., Furnary, A. P., Wu, Y., Wang, L., & Starr, A. (2012). Durability of pericardial versus porcine bioprosthetic heart valves. The Journal of Thoracic and Cardiovascular Surgery, 144, 1381–1386.

  6. 6.

    Makkar, R. R., Fontana, G., Jilaihawi, H., et al. (2015). Possible subclinical leaflet thrombosis in bioprosthetic aortic valves. The New England Journal of Medicine, 373, 2015–2024.

  7. 7.

    Shinoka, T., & Miyachi, H. (2016). Current status of tissue engineering heart valve. World Journal for Pediatric and Congenital Heart Surgery, 7, 677–684.

  8. 8.

    Emmert, M. Y., Schmitt, B. A., Loerakker, S., et al. (2018). Computational modeling guides tissue-engineered heart valve design for long-term in vivo performance in a translational sheep model. Science Translational Medicine, 10.

  9. 9.

    Zund, G., Breuer, C., Shinoka, T., et al. (1997). The in vitro construction of a tissue engineered bioprosthetic heart valve. European Journal of Cardio-Thoracic Surgery, 11, 493–497.

  10. 10.

    Emmert, M. Y., Weber, B., Behr, L., et al. (2014). Transcatheter aortic valve implantation using anatomically oriented, marrow stromal cell-based, stented, tissue-engineered heart valves: technical considerations and implications for translational cell-based heart valve concepts. European Journal of Cardio-Thoracic Surgery, 45, 61–68.

  11. 11.

    Tseng, H., Puperi, D. S., Kim, E. J., et al. (2014). Anisotropic poly(ethylene glycol)/polycaprolactone hydrogel–fiber composites for heart valve tissue engineering. Tissue Engineering Part A, 20, 2634–2645.

  12. 12.

    Yacoub, M. H., & Takkenberg, J. J. M. (2005). Will heart valve tissue engineering change the world? Nature Clinical Practice. Cardiovascular Medicine, 2, 60–61.

  13. 13.

    Takewa, Y., Sumikura, H., Kishimoto, S., et al. (2018). Implanted in-body tissue-engineered heart valve can adapt the histological structure to the environment. ASAIO Journal, 64, 395–405.

  14. 14.

    Reimer, J., Syedain, Z., Haynie, B., Lahti, M., Berry, J., & Tranquillo, R. (2017). Implantation of a tissue-engineered tubular heart valve in growing lambs. Annals of Biomedical Engineering, 45, 439–451.

  15. 15.

    Kluin, J., Talacua, H., Smits, A. I., et al. (2017). In situ heart valve tissue engineering using a bioresorbable elastomeric implant-from material design to 12 months follow-up in sheep. Biomaterials, 125, 101–117.

  16. 16.

    Jana, S., Tefft, B. J., Spoon, D. B., & Simari, R. D. (2014). Scaffolds for tissue engineering of cardiac valves. Acta Biomaterialia, 10, 2877–2893.

  17. 17.

    D’Amore, A., Luketich, S. K., Raffa, G. M., et al. (2018). Heart valve scaffold fabrication: bioinspired control of macro-scale morphology, mechanics and micro-structure. Biomaterials, 150, 25–37.

  18. 18.

    Hobson, C. M., Amoroso, N. J., Amini, R., et al. (2015). Fabrication of elastomeric scaffolds with curvilinear fibrous structures for heart valve leaflet engineering. Journal of Biomedical Materials Research. Part A, 103, 3101–3106.

  19. 19.

    Coyan, G. N., D’Amore, A., Matsumura, Y., et al. (2018). In vivo functional assessment of a novel degradable metal and elastomeric scaffold-based tissue engineered heart valve. The Journal of Thoracic and Cardiovascular Surgery.

  20. 20.

    Hong, Y., Fujimoto, K., Hashizume, R., et al. (2008). Generating elastic, biodegradable polyurethane/poly(lactide-co-glycolide) fibrous sheets with controlled antibiotic release via two-stream electrospinning. Biomacromolecules, 9, 1200–1207.

  21. 21.

    D’Amore, A., Stella, J. A., Wagner, W. R., & Sacks, M. S. (2010). Characterization of the complete fiber network topology of planar fibrous tissues and scaffolds. Biomaterials, 31, 5345–5354.

  22. 22.

    Hasan, A., Ragaert, K., Swieszkowski, W., et al. (2014). Biomechanical properties of native and tissue engineered heart valve constructs. Journal of Biomechanics, 47, 1949–1963.

  23. 23.

    Motta, S. E., Lintas, V., Fioretta, E. S., Hoerstrup, S. P., & Emmert, M. Y. (2018). Off-the-shelf tissue engineered heart valves for in situ regeneration: current state, challenges and future directions. Expert Review of Medical Devices, 15, 35–45.

  24. 24.

    Hasan, A., Saliba, J., Pezeshgi Modarres, H., et al. (2016). Micro and nanotechnologies in heart valve tissue engineering. Biomaterials, 103, 278–292.

  25. 25.

    Amoroso, N. J., D’Amore, A., Hong, Y., Wagner, W. R., & Sacks, M. S. (2011). Elastomeric electrospun polyurethane scaffolds: the interrelationship between fabrication conditions, fiber topology, and mechanical properties. Advanced Materials, 23, 106–111.

  26. 26.

    Syedain, Z., Reimer, J., Schmidt, J., et al. (2015). 6-month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep. Biomaterials, 73, 175–184.

  27. 27.

    Theodoridis, K., Tudorache, I., Cebotari, S., et al. (2017). Six-year-old sheep as a clinically relevant large animal model for aortic valve replacement using tissue-engineered grafts based on decellularized allogenic matrix. Tissue Engineering. Part C, Methods, 23, 953–963.

  28. 28.

    Amoroso, N. J., D’Amore, A., Hong, Y., Rivera, C. P., Sacks, M. S., & Wagner, W. R. (2012). Microstructural manipulation of electrospun scaffolds for specific bending stiffness for heart valve tissue engineering. Acta Biomaterialia, 8, 4268–4277.

  29. 29.

    Capulli, A. K., Emmert, M. Y., Pasqualini, F. S., et al. (2017). JetValve: rapid manufacturing of biohybrid scaffolds for biomimetic heart valve replacement. Biomaterials, 133, 229–241.

  30. 30.

    Kunadian, B., Vijayalakshmi, K., Thornley, A. R., et al. (2007). Meta-analysis of valve hemodynamics and left ventricular mass regression for stentless versus stented aortic valves. The Annals of Thoracic Surgery, 84, 73–78.

  31. 31.

    Clavel, M. A., Webb, J. G., Pibarot, P., et al. (2009). Comparison of the hemodynamic performance of percutaneous and surgical bioprostheses for the treatment of severe aortic stenosis. Journal of the American College of Cardiology, 53, 1883–1891.

  32. 32.

    Navia, J. L., Brozzi, N., Doi, K., et al. (2010). Implantation technique and early echocardiographic performance of newly designed stentless mitral bioprosthesis. ASAIO Journal, 56, 497–503.

  33. 33.

    Kainuma, S., Kasegawa, H., Miyagawa, S., et al. (2015). In vivo assessment of novel stentless valve in the mitral position. Circulation Journal, 79, 553–559.

  34. 34.

    Nishida, H., Kasegawa, H., Kin, H., & Takanashi, S. (2016). Early clinical outcome of mitral valve replacement using a newly designed stentless mitral valve for failure of initial mitral valve repair. The Heart Surgery Forum, 19, E306–E3E7.

  35. 35.

    Nistal, F., García-Martínez, V., Arbe, E., et al. (1990). In vivo experimental assessment of polytetrafluoroethylene trileaflet heart valve prosthesis. The Journal of Thoracic and Cardiovascular Surgery, 99, 1074–1081.

  36. 36.

    Fallon, A. M., Goodchild, T. T., Cox, J. L., & Matheny, R. G. (2014). In vivo remodeling potential of a novel bioprosthetic tricuspid valve in an ovine model. The Journal of Thoracic and Cardiovascular Surgery, 148, 333–40. e1.

  37. 37.

    Zafar, F., Hinton, R. B., Moore, R. A., et al. (2015). Physiological growth, remodeling potential, and preserved function of a novel bioprosthetic tricuspid valve: tubular bioprosthesis made of small intestinal submucosa-derived extracellular matrix. Journal of the American College of Cardiology, 66, 877–888.

  38. 38.

    Mosala Nezhad, Z., Poncelet, A., de Kerchove, L., et al. (2017). CorMatrix valved conduit in a porcine model: long-term remodelling and biomechanical characterization. Interactive Cardiovascular and Thoracic Surgery, 24, 90–98.

  39. 39.

    Zaidi, A. H., Nathan, M., Emani, S., et al. (2014). Preliminary experience with porcine intestinal submucosa (CorMatrix) for valve reconstruction in congenital heart disease: histologic evaluation of explanted valves. The Journal of Thoracic and Cardiovascular Surgery, 148, 2216–2214 25.e1.

  40. 40.

    Nelson, J. S., Heider, A., Si, M. S., & Ohye, R. G. (2016). Evaluation of explanted CorMatrix intracardiac patches in children with congenital heart disease. The Annals of Thoracic Surgery, 102, 1329–1335.

  41. 41.

    D’Amore, A., Yoshizumi, T., Luketich, S. K., et al. (2016). Bi-layered polyurethane-extracellular matrix cardiac patch improves ischemic ventricular wall remodeling in a rat model. Biomaterials, 107, 1–14.

  42. 42.

    Takanari, K., Hashizume, R., Hong, Y., et al. (2017). Skeletal muscle derived stem cells microintegrated into a biodegradable elastomer for reconstruction of the abdominal wall. Biomaterials, 113, 31–41.

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Acknowledgments

We would like to thank Joseph Hanke, Meegan Ambrose, and the rest of the excellent staff at the McGowan Center for Preclinical Studies for their assistance with animal care throughout this study. We would also like to thank the Center for Biological Imaging at the University of Pittsburgh for assistance with the scanning electron microscopy.

Funding

This work was supported by Wallace H. Coulter Foundation Translational Bioengineering Research Award, the Clinical and Translational Science Institute of the University of Pittsburgh, and the RiMED Foundation (grant 0057091).

Author information

Correspondence to Antonio D’Amore.

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Conflict of Interest

William Wagner, Antonio D’Amore, and Vinay Badhwar filed utility patents pertaining to the technology described in this manuscript. All the other authors declare that they have no conflict of interest.

Human Subjects

No human studies were carried out by the authors for this article.

Animal Studies

All experiments described in this manuscript were approved by the Institutional Animal Care and Use Committee of the University of Pittsburgh (protocol number: 16047811). Animals were cared for in accordance with the Guide for the Care and Use of Laboratory Animals as published by the National Institute of Health.

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Read at the 99th Annual Meeting of the American Association for Thoracic Surgery on May 5, 2019.

Associate Editor Marat Fudim oversaw the review of this article

Electronic Supplementary Material

Supplemental Figure 1
figure7

Operative implantation of the stentless tissue engineered tricuspid valve. (A) The valve is sutured in using a continuous polypropylene suture technique to the native tricuspid annulus on beating heart cardiopulmonary bypass. (B) The implanted tissue engineered tricuspid valve in the native tricuspid annulus (green arrow) (PNG 923 kb)

High Resolution Image (TIF 601 kb)

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Coyan, G.N., da Mota Silveira-Filho, L., Matsumura, Y. et al. Acute In Vivo Functional Assessment of a Biodegradable Stentless Elastomeric Tricuspid Valve. J. of Cardiovasc. Trans. Res. (2020). https://doi.org/10.1007/s12265-020-09960-z

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Keywords

  • Tissue-engineered heart valve
  • Tricuspid valve replacement
  • Double-component deposition
  • Electrospinning
  • In vivo study
  • Biodegradable valve prosthesis