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


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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Double-component deposition


Epicardial echocardiography


Poly(carbonate urethane)urea


Scanning electron micrography


Tissue-engineered heart valve


  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  3. 3.

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

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  24. 24.

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

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  Article  Google Scholar 

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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.


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).

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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

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Supplemental Figure 1

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)

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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. 13, 796–805 (2020).

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