Skip to main content

Advertisement

SpringerLink
Log in

Translational Challenges in Cardiovascular Tissue Engineering

  • Original Article
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Valvular heart disease and congenital heart defects represent a major cause of death around the globe. Although current therapy strategies have rapidly evolved over the decades and are nowadays safe, effective, and applicable to many affected patients, the currently used artificial prostheses are still suboptimal. They do not promote regeneration, physiological remodeling, or growth (particularly important aspects for children) as their native counterparts. This results in the continuous degeneration and subsequent failure of these prostheses which is often associated with an increased morbidity and mortality as well as the need for multiple re-interventions. To overcome this problem, the concept of tissue engineering (TE) has been repeatedly suggested as a potential technology to enable native-like cardiovascular replacements with regenerative and growth capacities, suitable for young adults and children. However, despite promising data from pre-clinical and first clinical pilot trials, the translation and clinical relevance of such TE technologies is still very limited. The reasons that currently limit broad clinical adoption are multifaceted and comprise of scientific, clinical, logistical, technical, and regulatory challenges which need to be overcome. The aim of this review is to provide an overview about the translational problems and challenges in current TE approaches. It further suggests directions and potential solutions on how these issues may be efficiently addressed in the future to accelerate clinical translation. In addition, a particular focus is put on the current regulatory guidelines and the associated challenges for these promising TE technologies.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

EC:

Endothelial cell

ECM:

Extracellular matrix

GCP:

Good clinical practice

GLP:

Good laboratory practice

GMP:

Good manufacturing practice

ISO:

International Organization for Standardization

SOP:

Standard operating procedure

TE:

Tissue engineering

TEMP:

Tissue engineered medical product

References

  1. Marelli, A. J., Mackie, A. S., Ionescu-Ittu, R., Rahme, E., & Pilote, L. (2007). Congenital heart disease in the general population: changing prevalence and age distribution. Circulation, 115(2), 163–172. doi:10.1161/CIRCULATIONAHA.106.627224.

    Article  PubMed  Google Scholar 

  2. Nkomo, V. T., Gardin, J. M., Skelton, T. N., Gottdiener, J. S., Scott, C. G., & Enriquez-Sarano, M. Burden of valvular heart diseases: a population-based study. The Lancet, 368(9540), 1005–1011. doi:10.1016/S0140-6736(06)69208-8.

  3. Supino, P. G., Borer, J. S., Preibisz, J., & Bornstein, A. (2006). The epidemiology of valvular heart disease: a growing public health problem. Heart Failure Clinics, 2(4), 379–393. doi:10.1016/j.hfc.2006.09.010.

    Article  PubMed  Google Scholar 

  4. Cribier, A., Eltchaninoff, H., Bash, A., Borenstein, N., Tron, C., Bauer, F., et al. (2002). Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation, 106(24), 3006–3008.

    Article  PubMed  Google Scholar 

  5. Fioretta, E. S., Dijkman, P. E., Emmert, M. Y., & Hoerstrup, S. P. (2016). The future of heart valve replacement: recent developments and translational challenges for heart valve tissue engineering. Journal of Tissue Engineering and Regenerative Medicine. doi:10.1002/term.2326.

    PubMed  Google Scholar 

  6. Schoen, F. J., & Gotlieb, A. I. (2016). Heart valve health, disease, replacement, and repair: a 25-year cardiovascular pathology perspective. Cardiovascular Pathology, 25(4), 341–352. doi:10.1016/j.carpath.2016.05.002.

    Article  PubMed  Google Scholar 

  7. Alexi-Meskishvilia, V., Ovroutskib, S., Ewertb, P., DaÈhnertb, I., Bergerb, F., Langeb, P. E., et al. (2000). Optimal conduit size for extracardiac Fontan operation. European Journal of Cardio-Thoracic Surgery, 18(690–695).

  8. Yacoub, M. H., & Takkenberg, J. J. (2005). Will heart valve tissue engineering change the world? Nature Clinical Practice. Cardiovascular Medicine, 2(2), 60–61. doi:10.1038/ncpcardio0112.

    Article  CAS  PubMed  Google Scholar 

  9. Mendelson, K., & Schoen, F. J. (2006). Heart valve tissue engineering: concepts, approaches, progress, and challenges. Annals of Biomedical Engineering, 34(12), 1799–1819. doi:10.1007/s10439-006-9163-z.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Langer, R., & Vacanti, J. P. (1993). Tissue engineering. Science, 260(5110), 920–926.

    Article  CAS  PubMed  Google Scholar 

  11. Dohmen, P. M., Lembcke, A., Hotz, H., Kivelitz, D., & Konertz, W. F. (2002). Ross operation with a tissue-engineered heart valve. The Annals of Thoracic Surgery, 74(5), 1438–1442.

    Article  PubMed  Google Scholar 

  12. Dohmen, P. M., Lembcke, A., Holinski, S., Pruss, A., & Konertz, W. (2011). Ten years of clinical results with a tissue-engineered pulmonary valve. The Annals of Thoracic Surgery, 92(4), 1308–1314. doi:10.1016/j.athoracsur.2011.06.009.

    Article  PubMed  Google Scholar 

  13. Cebotari, S., Lichtenberg, A., Tudorache, I., Hilfiker, A., Mertsching, H., Leyh, R., et al. (2006). Clinical application of tissue engineered human heart valves using autologous progenitor cells. Circulation, 114(1 Suppl), I132–I137. doi:10.1161/CIRCULATIONAHA.105.001065.

    PubMed  Google Scholar 

  14. Dohmen, P. M., Lembcke, A., Holinski, S., Kivelitz, D., Braun, J. P., Pruss, A., et al. (2007). Mid-term clinical results using a tissue-engineered pulmonary valve to reconstruct the right ventricular outflow tract during the Ross procedure. The Annals of Thoracic Surgery, 84(3), 729–736. doi:10.1016/j.athoracsur.2007.04.072.

    Article  PubMed  Google Scholar 

  15. Naito, Y., Imai, Y., Shin’oka, T., Kashiwagi, J., Aoki, M., Watanabe, M., et al. (2003). Successful clinical application of tissue-engineered graft for extracardiac Fontan operation. The Journal of Thoracic and Cardiovascular Surgery, 125(2), 419–420. doi:10.1067/mtc.2003.134.

    Article  PubMed  Google Scholar 

  16. Shinoka, T., & Breuer, C. (2008). Tissue-engineered blood vessels in pediatric cardiac surgery. Yale Journal of Biology and Medicine, 81, 161–166.

    PubMed  PubMed Central  Google Scholar 

  17. Bouten, C. V., Dankers, P. Y., Driessen-Mol, A., Pedron, S., Brizard, A. M., & Baaijens, F. P. (2011). Substrates for cardiovascular tissue engineering. Advanced Drug Delivery Reviews, 63(4–5), 221–241. doi:10.1016/j.addr.2011.01.007.

    Article  CAS  PubMed  Google Scholar 

  18. Fioretta, E. S., Fledderus, J. O., Burakowska-Meise, E. A., Baaijens, F. P., Verhaar, M. C., & Bouten, C. V. (2012). Polymer-based scaffold designs for in situ vascular tissue engineering: controlling recruitment and differentiation behavior of endothelial colony forming cells. Macromolecular Bioscience, 12(5), 577–590. doi:10.1002/mabi.201100315.

    Article  CAS  PubMed  Google Scholar 

  19. Dijkman, P. E., Fioretta, E. S., Frese, L., Pasqualini, F. S., & Hoerstrup, S. P. (2016). Heart valve replacements with regenerative capacity. Transfusion Medicine and Hemotherapy, 43(4), 282–290. doi:10.1159/000448181.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Cheung, D. Y., Duan, B., & Butcher, J. T. (2015). Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions. Expert opinion on biological therapy. [early online].

  21. Jana, S., Tefft, B. J., Spoon, D. B., & Simari, R. D. (2014). Scaffolds for tissue engineering of cardiac valves. Acta Biomaterialia, 10(7), 2877–2893. doi:10.1016/j.actbio.2014.03.014.

    Article  CAS  PubMed  Google Scholar 

  22. Kurobe, H., Maxfield, M. W., Breuer, C. K., & Shinoka, T. (2012). Concise review: tissue-engineered vascular grafts for cardiac surgery: past, present, and future. Stem Cells Transl Med, 1(7), 566–571. doi:10.5966/sctm.2012-0044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Patterson, J. T., Gilliland, T., Maxfield, M. W., Church, S., Naito, Y., Shinoka, T., et al. (2012). Tissue-engineered vascular grafts for use in the treatment of congenital heart disease: from the bench to the clinic and back again. Regenerative Medicine, 7(3), 409–419. doi:10.2217/rme.12.12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Fioretta, E. S., Fledderus, J. O., Baaijens, F. P., & Bouten, C. V. (2012). Influence of substrate stiffness on circulating progenitor cell fate. Journal of Biomechanics, 45(5), 736–744. doi:10.1016/j.jbiomech.2011.11.013.

    Article  PubMed  Google Scholar 

  25. Tudorache, I., Horke, A., Cebotari, S., Sarikouch, S., Boethig, D., Breymann, T., et al. (2016). Decellularized aortic homografts for aortic valve and aorta ascendens replacement. European Journal of Cardio-Thoracic Surgery, 50(1), 89–97. doi:10.1093/ejcts/ezw013.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sarikouch, S., Horke, A., Tudorache, I., Beerbaum, P., Westhoff-Bleck, M., Boethig, D., et al. (2016). Decellularized fresh homografts for pulmonary valve replacement: a decade of clinical experience. European Journal of Cardio-Thoracic Surgery. doi:10.1093/ejcts/ezw050.

    Google Scholar 

  27. Neumann, A., Cebotari, S., Tudorache, I., Haverich, A., & Sarikouch, S. (2013). Heart valve engineering: decellularized allograft matrices in clinical practice. Biomed Tech (Berl), 58(5), 453–456. doi:10.1515/bmt-2012-0115.

    Article  Google Scholar 

  28. Cebotari, S., Tudorache, I., Ciubotaru, A., Boethig, D., Sarikouch, S., Goerler, A., et al. (2011). Use of fresh decellularized allografts for pulmonary valve replacement may reduce the reoperation rate in children and young adults: early report. Circulation, 124(11 Suppl), S115–S123. doi:10.1161/CIRCULATIONAHA.110.012161.

    Article  PubMed  Google Scholar 

  29. da Costa, F. D. A., Costa, A. C. B. A., Prestes, R., Domanski, A. C., Balbi, E. M., Ferreira, A. D. A., et al. (2010). The early and midterm function of decellularized aortic valve allografts. The Annals of Thoracic Surgery, 90(6), 1854–1860. doi:10.1016/j.athoracsur.2010.08.022.

    Article  PubMed  Google Scholar 

  30. Hoerstrup, S. P., Sodian, R., Daebritz, S., Wang, J., Bacha, E. A., Martin, D. P., et al. (2000). Functional living trileaflet heart valves grown in vitro. Circulation, 102(19 Suppl 3), III44–III49.

    CAS  PubMed  Google Scholar 

  31. Hoerstrup, S. P., Cummings Mrcs, I., Lachat, M., Schoen, F. J., Jenni, R., Leschka, S., et al. (2006). Functional growth in tissue-engineered living, vascular grafts: follow-up at 100 weeks in a large animal model. Circulation, 114(1 Suppl), I159–I166. doi:10.1161/CIRCULATIONAHA.105.001172.

    PubMed  Google Scholar 

  32. Shinoka, T., Ma, P. X., Shum-Tim, D., Breuer, C. K., Cusick, R. A., Zund, G., et al. (1996). Tissue-engineered heart valves. Autologous valve leaflet replacement study in a lamb model. Circulation, 94(9), II164–II168.

    CAS  PubMed  Google Scholar 

  33. Weber, B., Scherman, J., Emmert, M. Y., Gruenenfelder, J., Verbeek, R., Bracher, M., et al. (2011). Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates. European Heart Journal, 32(22), 2830–2840. doi:10.1093/eurheartj/ehr059.

    Article  PubMed  Google Scholar 

  34. Driessen-Mol, A., Emmert, M. Y., Dijkman, P. E., Frese, L., Sanders, B., Weber, B., et al. (2014). Transcatheter implantation of homologous “off-the-shelf” tissue-engineered heart valves with self-repair capacity: long-term functionality and rapid in vivo remodeling in sheep. Journal of the American College of Cardiology, 63(13), 1320–1329. doi:10.1016/j.jacc.2013.09.082.

    Article  PubMed  Google Scholar 

  35. Syedain, Z., Reimer, J., Schmidt, J., Lahti, M., Berry, J., Bianco, R., et al. (2015). 6-month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep. Biomaterials, 73, 175–184. doi:10.1016/j.biomaterials.2015.09.016.

    Article  CAS  PubMed  Google Scholar 

  36. Syedain, Z., Reimer, J., Lahti, M., Berry, J., Johnson, S., & Tranquillo, R. T. (2016). Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs. Nature Communications, 7, 12951. doi:10.1038/ncomms12951.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sievers, H.-H., Stierle, U., Schmidtke, C., & Bechtel, M. (2003). Decellularized pulmonary homograft (SynerGraft) for reconstruction of the right ventricular outflow tract: first clinical experience. [journal article]. Zeitschrift für Kardiologie, 92(1), 53–59. doi:10.1007/s00392-003-0883-x.

    Article  PubMed  Google Scholar 

  38. Hibino, N., McConnell, P., Shinoka, T., Malik, M., & Galantowicz, M. (2015). Preliminary experience in the use of an extracellular matrix (CorMatrix) as a tube graft: word of caution. Seminars in thoracic and cardiovascular surgery, doi:10.1053/j.semtcvs.2015.08.008.

  39. Iop, L., & Gerosa, G. (2015). Guided tissue regeneration in heart valve replacement: from preclinical research to first-in-human trials. BioMed Research International, 2015, 432901. doi:10.1155/2015/432901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Salmikangas, P., Schuessler-Lenz, M., Ruiz, S., Celis, P., Reischl, I., Menezes-Ferreira, M., et al. (2015). Marketing regulatory oversight of advanced therapy medicinal products (ATMPs) in Europe: the EMA/CAT perspective. Advances in Experimental Medicine and Biology, 871, 103–130. doi:10.1007/978-3-319-18618-4_6.

    Article  PubMed  Google Scholar 

  41. Yano, K., Watanabe, N., Tsuyuki, K., Ikawa, T., Kasanuki, H., & Yamato, M. (2015). Regulatory approval for autologous human cells and tissue products in the United States, the European Union, and Japan. Regenerative Therapy, 1, 45–56. doi:10.1016/j.reth.2014.10.001.

    Article  Google Scholar 

  42. Sanzenbacher, R., Dwenger, A., Schuessler-Lenz, M., Cichutek, K., & Flory, E. (2007). European regulation tackles tissue engineering. Nat Biotech, 25(10), 1089–1091.

    Article  CAS  Google Scholar 

  43. Commission Directive 2009/120/EC of 14 September 2009 amending Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use as regards advanced therapy medicinal products (2009). Official Journal of the European Union, 242, 3).

  44. Lee, M. H., Arcidiacono, J. A., Bilek, A. M., Wille, J. J., Hamill, C. A., Wonnacott, K. M., et al. (2010). Considerations for tissue-engineered and regenerative medicine product development prior to clinical trials in the United States. Tissue Engineering. Part B, Reviews, 16(1), 41–54.

    Article  CAS  PubMed  Google Scholar 

  45. Lu, L., Arbit, H. M., Herrick, J. L., Segovis, S. G., Maran, A., & Yaszemski, M. J. (2015). Tissue engineered constructs: perspectives on clinical translation. Annals of Biomedical Engineering, 43(3), 796–804. doi:10.1007/s10439-015-1280-0.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Law, E. U. (2012). Proposal for a regulation of the European Parliament and of the council on medical devices. EUR-Lex, 52012PC0542, http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=celex:52012PC50542.

  47. Lichtenberg, A., Tudorache, I., Cebotari, S., Suprunov, M., Tudorache, G., Goerler, H., et al. (2006). Preclinical testing of tissue-engineered heart valves re-endothelialized under simulated physiological conditions. Circulation, 114(1 Suppl), I559–I565. doi:10.1161/CIRCULATIONAHA.105.001206.

    PubMed  Google Scholar 

  48. Baraki, H., Tudorache, I., Braun, M., Hoffler, K., Gorler, A., Lichtenberg, A., et al. (2009). Orthotopic replacement of the aortic valve with decellularized allograft in a sheep model. Biomaterials, 30(31), 6240–6246. doi:10.1016/j.biomaterials.2009.07.068.

    Article  CAS  PubMed  Google Scholar 

  49. Iop, L., Bonetti, A., Naso, F., Rizzo, S., Cagnin, S., Bianco, R., et al. (2014). Decellularized allogeneic heart valves demonstrate self-regeneration potential after a long-term preclinical evaluation. PloS One, 9(6), e99593. doi:10.1371/journal.pone.0099593.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Row, S., Peng, H., Schlaich, E. M., Koenigsknecht, C., Andreadis, S. T., & Swartz, D. D. (2015). Arterial grafts exhibiting unprecedented cellular infiltration and remodeling in vivo: the role of cells in the vascular wall. Biomaterials, 50, 115–126. doi:10.1016/j.biomaterials.2015.01.045.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Koobatian, M. T., Row, S., Smith Jr., R. J., Koenigsknecht, C., Andreadis, S. T., & Swartz, D. D. (2016). Successful endothelialization and remodeling of a cell-free small-diameter arterial graft in a large animal model. Biomaterials, 76, 344–358. doi:10.1016/j.biomaterials.2015.10.020.

    Article  CAS  PubMed  Google Scholar 

  52. Simon, P., Kasimir, M. T., Seebacher, G., Weigel, G., Allrich, R., Salzer-Muhar, U., et al. (2003). Early failure of the tissue engineered porcine heart valve SYNERGRAFT in pediatric patients. European Journal of Cardio-Thoracic Surgery, 23(6), 1002–1006.

    Article  CAS  PubMed  Google Scholar 

  53. Voges, I., Brasen, J. H., Entenmann, A., Scheid, M., Scheewe, J., Fischer, G., et al. (2013). Adverse results of a decellularized tissue-engineered pulmonary valve in humans assessed with magnetic resonance imaging. European Journal of Cardio-Thoracic Surgery, 44(4), e272–e279. doi:10.1093/ejcts/ezt328.

    Article  PubMed  Google Scholar 

  54. Ruffer, A., Purbojo, A., Cicha, I., Glockler, M., Potapov, S., Dittrich, S., et al. (2010). Early failure of xenogenous de-cellularised pulmonary valve conduits—a word of caution! European Journal of Cardio-Thoracic Surgery, 38(1), 78–85. doi:10.1016/j.ejcts.2010.01.044.

    Article  PubMed  Google Scholar 

  55. Woo, J. S., Fishbein, M. C., & Reemtsen, B. (2015). Histologic examination of decellularized porcine intestinal submucosa extracellular matrix (CorMatrix) in pediatric congenital heart surgery. Cardiovascular Pathology. doi:10.1016/j.carpath.2015.08.007.

    PubMed  Google Scholar 

  56. Watanabe, M., Shin’oka, T., Tohyama, S., Hibino, N., Konuma, T., Matsumura, G., et al. (2001). Tissue-engineered vascular autograft: inferior vena cava replacement in a dog model. Tissue Engineering, 7(4), 429–439.

    Article  CAS  PubMed  Google Scholar 

  57. Hoerstrup, S. P., Kadner, A., Melnitchouk, S., Trojan, A., Eid, K., Tracy, J., et al. (2002). Tissue engineering of functional trileaflet heart valves from human marrow stromal cells. Circulation, 106(suppl I), I-143–I-150. doi:10.1161/01.cir.0000032872.55215.05.

    Google Scholar 

  58. Frese, L., Sanders, B., Beer, G. M., Weber, B., Driessen-Mol, A., Baaijens, F. P. T., et al. (2015). Adipose derived tissue engineered heart valve. Journal of Tissue Science & Engineering, 06(03). doi:10.4172/2157-7552.1000156.

  59. Sodian, R., Schaefermeier, P., Begg-Zips, S., Kuebler, W. M., Shakibaei, M., & Daebritz, S. (2010). Use of human umbilical cord blood-derived progenitor cells for tissue-engineered heart valves. Ann.Thorac.Surg., 89(3), 819–828.

    Article  PubMed  Google Scholar 

  60. Bayon, Y., Vertes, A. A., Ronfard, V., Egloff, M., Snykers, S., Salinas, G. F., et al. (2014). Translating cell-based regenerative medicines from research to successful products: challenges and solutions. Tissue Engineering. Part B, Reviews, 20(4), 246–256. doi:10.1089/ten.TEB.2013.0727.

    Article  PubMed  Google Scholar 

  61. Fioretta, E. S., Simonet, M., Smits, A. I., Baaijens, F. P., & Bouten, C. V. (2014). Differential response of endothelial and endothelial colony forming cells on electrospun scaffolds with distinct microfiber diameters. Biomacromolecules, 15(3), 821–829. doi:10.1021/bm4016418.

    Article  CAS  PubMed  Google Scholar 

  62. Nisbet, D. R., Forsythe, J. S., Shen, W., Finkelstein, D. I., & Horne, M. K. (2009). Review paper: a review of the cellular response on electrospun nanofibers for tissue engineering. Journal of Biomaterials Applications, 24(1), 7–29.

    Article  CAS  PubMed  Google Scholar 

  63. Jana, S., Tranquillo, R. T., & Lerman, A. (2016). Cells for tissue engineering of cardiac valves. Journal of Tissue Engineering and Regenerative Medicine, 10(10), 804–824. doi:10.1002/term.2010.

    Article  CAS  PubMed  Google Scholar 

  64. da Costa, F. D., Dohmen, P. M., Duarte, D., von Glenn, C., Lopes, S. V., Filho, H. H., et al. (2005). Immunological and echocardiographic evaluation of decellularized versus cryopreserved allografts during the Ross operation. European Journal of Cardio-Thoracic Surgery, 27(4), 572–578. doi:10.1016/j.ejcts.2004.12.057.

    Article  PubMed  Google Scholar 

  65. Dijkman, P. E., Driessen-Mol, A., Frese, L., Hoerstrup, S. P., & Baaijens, F. P. (2012). Decellularized homologous tissue-engineered heart valves as off-the-shelf alternatives to xeno- and homografts. Biomaterials, 33(18), 4545–4554. doi:10.1016/j.biomaterials.2012.03.015.

    Article  CAS  PubMed  Google Scholar 

  66. Syedain, Z. H., Meier, L. A., Reimer, J. M., & Tranquillo, R. T. (2013). Tubular heart valves from decellularized engineered tissue. Annals of Biomedical Engineering, 41(12), 2645–2654. doi:10.1007/s10439-013-0872-9.

    Article  PubMed  Google Scholar 

  67. Melchiorri, A. J., Hibino, N., Yi, T., Lee, Y. U., Sugiura, T., Tara, S., et al. (2015). Contrasting biofunctionalization strategies for the enhanced endothelialization of biodegradable vascular grafts. Biomacromolecules, 16(2), 437–446. doi:10.1021/bm501853s.

    Article  CAS  PubMed  Google Scholar 

  68. Tara, S., Kurobe, H., Maxfield, M. W., Rocco, K. A., Yi, T., Naito, Y., et al. (2015). Evaluation of remodeling process in small-diameter cell-free tissue-engineered arterial graft. Journal of Vascular Surgery, 62(3), 734–743. doi:10.1016/j.jvs.2014.03.011.

    Article  PubMed  Google Scholar 

  69. Talacua, H., Smits, A. I., Muylaert, D. E., van Rijswijk, J. W., Vink, A., Verhaar, M. C., et al. (2015). In situ tissue engineering of functional small-diameter blood vessels by host circulating cells only. Tissue Engineering. Part A, 21(19–20), 2583–2594. doi:10.1089/ten.TEA.2015.0066.

    Article  CAS  PubMed  Google Scholar 

  70. Ekdahl, K. N., Lambris, J. D., Elwing, H., Ricklin, D., Nilsson, P. H., Teramura, Y., et al. (2011). Innate immunity activation on biomaterial surfaces: a mechanistic model and coping strategies. Advanced Drug Delivery Reviews, 63(12), 1042–1050. doi:10.1016/j.addr.2011.06.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Smyth, J. V., Welch, M., Carr, H. M., Dodd, P. D., Eisenberg, P. R., & Walker, M. G. (1995). Fibrinolysis profiles and platelet activation after endothelial cell seeding of prosthetic vascular grafts. Annals of Vascular Surgery, 9(6), 542–546. doi:10.1007/BF02018827.

    Article  CAS  PubMed  Google Scholar 

  72. Laube, H. R., Duwe, J., Rutsch, W., & Konertz, W. (2000). Clinical experience with autologous endothelial cell-seeded polytetrafluoroethylene coronary artery bypass grafts. The Journal of Thoracic and Cardiovascular Surgery, 120(1), 134–141. doi:10.1067/mtc.2000.106327.

    Article  CAS  PubMed  Google Scholar 

  73. Zilla, P., Fasol, R., Deutsch, M., Fischlein, T., Minar, E., Hammerle, A., et al. (1987). Endothelial cell seeding of polytetrafluoroethylene vascular grafts in humans: a preliminary report. Journal of Vascular Surgery, 6(6), 535–541. doi:10.1016/0741-5214(87)90266-7.

    Article  CAS  PubMed  Google Scholar 

  74. Herring, M. B. (1991). Endothelial cell seeding. Journal of Vascular Surgery, 13(5), 731–732. doi:10.1016/0741-5214(91)90365-2.

    Article  CAS  PubMed  Google Scholar 

  75. Shi, Z., Neoh, K. G., & Kang, E. T. (2013). In vitro endothelialization of cobalt chromium alloys with micro/nanostructures using adipose-derived stem cells. Journal of Materials Science: Materials in Medicine, 24(4), 1067–1077. doi:10.1007/s10856-013-4868-7.

    CAS  PubMed  Google Scholar 

  76. Kim, Y., & Liu, J. C. (2016). Protein-engineered microenvironments can promote endothelial differentiation of human mesenchymal stem cells in the absence of exogenous growth factors. Biomaterials Science, 4(12), 1761–1772. doi:10.1039/C6BM00472E.

    Article  CAS  PubMed  Google Scholar 

  77. Melchiorri, A. J., Hibino, N., & Fisher, J. P. (2013). Strategies and techniques to enhance the in situ endothelialization of small-diameter biodegradable polymeric vascular grafts. Tissue Engineering. Part B, Reviews, 19(4), 292–307. doi:10.1089/ten.TEB.2012.0577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lin, Q., Ding, X., Qiu, F., Song, X., Fu, G., & Ji, J. (2010). In situ endothelialization of intravascular stents coated with an anti-CD34 antibody functionalized heparin-collagen multilayer. Biomaterials, 31(14), 4017–4025. doi:10.1016/j.biomaterials.2010.01.092.

    Article  CAS  PubMed  Google Scholar 

  79. Rotmans, J. I., Heyligers, J. M., Verhagen, H. J., Velema, E., Nagtegaal, M. M., de Kleijn, D. P., et al. (2005). In vivo cell seeding with anti-CD34 antibodies successfully accelerates endothelialization but stimulates intimal hyperplasia in porcine arteriovenous expanded polytetrafluoroethylene grafts. Circulation, 112(1), 12–18. doi:10.1161/CIRCULATIONAHA.104.504407.

    Article  CAS  PubMed  Google Scholar 

  80. Lu, S., Zhang, P., Sun, X., Gong, F., Yang, S., Shen, L., et al. (2013). Synthetic ePTFE grafts coated with an anti-CD133 antibody-functionalized heparin/collagen multilayer with rapid in vivo endothelialization properties. ACS Applied Materials & Interfaces, 5(15), 7360–7369. doi:10.1021/am401706w.

    Article  CAS  Google Scholar 

  81. Jordan, J. E., Williams, J. K., Lee, S. J., Raghavan, D., Atala, A., & Yoo, J. J. (2012). Bioengineered self-seeding heart valves. The Journal of Thoracic and Cardiovascular Surgery, 143(1), 201–208. doi:10.1016/j.jtcvs.2011.10.005.

    Article  PubMed  Google Scholar 

  82. Ravi, S., Qu, Z., & Chaikof, E. L. (2009). Polymeric materials for tissue engineering of arterial substitutes. Vascular, 17(Supplement 1), S45-S54, doi:10.2310/6670.2008.00084.

  83. Zheng, W., Wang, Z., Song, L., Zhao, Q., Zhang, J., Li, D., et al. (2012). Endothelialization and patency of RGD-functionalized vascular grafts in a rabbit carotid artery model. Biomaterials, 33(10), 2880–2891. doi:10.1016/j.biomaterials.2011.12.047.

    Article  CAS  PubMed  Google Scholar 

  84. Caiado, F., Carvalho, T., Silva, F., Castro, C., Clode, N., Dye, J. F., et al. (2011). The role of fibrin E on the modulation of endothelial progenitors adhesion, differentiation and angiogenic growth factor production and the promotion of wound healing. Biomaterials, 32(29), 7096–7105. doi:10.1016/j.biomaterials.2011.06.022.

    Article  CAS  PubMed  Google Scholar 

  85. Rodenberg, E. J., & Pavalko, F. M. (2007). Peptides derived from fibronectin type III connecting segments promote endothelial cell adhesion but not platelet adhesion: implications in tissue-engineered vascular grafts. Tissue Engineering, 13(11), 2653–2666. doi:10.1089/ten.2007.0037.

    Article  CAS  PubMed  Google Scholar 

  86. Jun, H.-W., & West, J. L. (2005). Modification of polyurethaneurea with PEG and YIGSR peptide to enhance endothelialization without platelet adhesion. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 72B(1), 131–139. doi:10.1002/jbm.b.30135.

    Article  CAS  Google Scholar 

  87. Aubin, H., Mas-Moruno, C., Iijima, M., Schutterle, N., Steinbrink, M., Assmann, A., et al. (2016). Customized interface biofunctionalization of decellularized extracellular matrix: toward enhanced endothelialization. Tissue Engineering. Part C, Methods, 22(5), 496–508. doi:10.1089/ten.TEC.2015.0556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Liu, P., Zhao, Y., Yan, Y., Hu, Y., Yang, W., & Cai, K. (2015). Construction of extracellular microenvironment to improve surface endothelialization of NiTi alloy substrate. Mater Sci Eng C Mater Biol Appl, 55, 1–7. doi:10.1016/j.msec.2015.05.047.

    Article  PubMed  Google Scholar 

  89. Smith Jr., R. J., Koobatian, M. T., Shahini, A., Swartz, D. D., & Andreadis, S. T. (2015). Capture of endothelial cells under flow using immobilized vascular endothelial growth factor. Biomaterials, 51, 303–312. doi:10.1016/j.biomaterials.2015.02.025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Wang, H., Leinwand, L. A., & Anseth, K. S. (2014). Cardiac valve cells and their microenvironment—insights from in vitro studies. Nature Reviews. Cardiology, 11(12), 715–727. doi:10.1038/nrcardio.2014.162.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Yin, Y., Zhao, X., Fang, Y., Yu, S., Zhao, J., Song, M., et al. (2010). SDF-1α involved in mobilization and recruitment of endothelial progenitor cells after arterial injury in mice. Cardiovascular Pathology, 19(4), 218–227. doi:10.1016/j.carpath.2009.04.002.

    Article  CAS  PubMed  Google Scholar 

  92. Liu, T., Liu, S., Zhang, K., Chen, J., & Huang, N. (2014). Endothelialization of implanted cardiovascular biomaterial surfaces: the development from in vitro to in vivo. Journal of Biomedical Materials Research. Part A, 102(10), 3754–3772. doi:10.1002/jbm.a.35025.

    Article  PubMed  Google Scholar 

  93. Emmert, M. Y., & Hoerstrup, S. P. (2016). Tissue engineered heart valves: moving towards clinical translation. Expert Review of Medical Devices, 13(5), 417–419. doi:10.1586/17434440.2016.1171709.

    Article  CAS  PubMed  Google Scholar 

  94. Beebe, D. J., Ingber, D. E., & den Toonder, J. (2013). Organs on chips 2013. Lab on a Chip, 13(18), 3447–3448. doi:10.1039/c3lc90080k.

    Article  CAS  PubMed  Google Scholar 

  95. Ram-Liebig, G., Bednarz, J., Stuerzebecher, B., Fahlenkamp, D., Barbagli, G., Romano, G., et al. (2015). Regulatory challenges for autologous tissue engineered products on their way from bench to bedside in Europe. Advanced Drug Delivery Reviews, 82-83, 181–191. doi:10.1016/j.addr.2014.11.009.

    Article  CAS  PubMed  Google Scholar 

  96. Hurtado-Aguilar, L. G., Mulderrig, S., Moreira, R., Hatam, N., Spillner, J., Schmitz-Rode, T., et al. (2016). Ultrasound for in vitro noninvasive, real time monitoring and evaluation of tissue-engineered heart valves. Tissue Engineering. Part C, Methods. doi:10.1089/ten.TEC.2016.0300.

    PubMed  Google Scholar 

  97. Ozaki, S., Herijgers, P., & Flameng, W. (2004). A new model to test the calcification characteristics of bioprosthetic heart valves. Annals of Thoracic and Cardiovascular Surgery, 10, 23–28.

    PubMed  Google Scholar 

  98. Taramasso, M., Emmert, M. Y., Reser, D., Guidotti, A., Cesarovic, N., Campagnol, M., et al. (2015). Pre-clinical in vitro and in vivo models for heart valve therapies. Journal of Cardiovascular Translational Research, 8(5), 319–327. doi:10.1007/s12265-015-9631-7.

    Article  PubMed  Google Scholar 

  99. Yuan, S. M., Mishaly, D., Shinfeld, A., & Raanani, E. (2008). Right ventricular outflow tract reconstruction: valved conduit of choice and clinical outcomes. Journal of Cardiovascular Medicine, 9, 327–337.

    Article  PubMed  Google Scholar 

  100. Bayon, Y., Vertes, A. A., Ronfard, V., Culme-Seymour, E., Mason, C., Stroemer, P., et al. (2015). Turning regenerative medicine breakthrough ideas and innovations into commercial products. Tissue Engineering. Part B, Reviews, 21(6), 560–571. doi:10.1089/ten.TEB.2015.0068.

    Article  PubMed  Google Scholar 

  101. de Wilde, S., Guchelaar, H. J., Herberts, C., Lowdell, M., Hildebrandt, M., Zandvliet, M., et al. (2016). Development of cell therapy medicinal products by academic institutes. Drug Discovery Today, 21(8), 1206–1212. doi:10.1016/j.drudis.2016.04.016.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors have received funding support from the European FP 7 Framework Programme under grant agreement no. 604514 (ImaValve).

Author information

Authors and Affiliations

  1. Institute for Regenerative Medicine (IREM), University of Zurich, Moussonstrasse 13, 8091, Zurich, Switzerland

    Maximilian Y. Emmert, Emanuela S. Fioretta & Simon P. Hoerstrup

  2. Heart Center Zurich, University Hospital Zurich, Zurich, Switzerland

    Maximilian Y. Emmert

  3. Wyss Translational Center Zurich, Zurich, Switzerland

    Maximilian Y. Emmert & Simon P. Hoerstrup

Authors
  1. Maximilian Y. Emmert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emanuela S. Fioretta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Simon P. Hoerstrup
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simon P. Hoerstrup.

Ethics declarations

Conflict of Interest

The authors declare that they have no competing interests.

Additional information

Associate Editor Adrian Chester oversaw the review of this article

Maximilian Y. Emmert and Emanuela S. Fioretta contributed equally.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Emmert, M.Y., Fioretta, E.S. & Hoerstrup, S.P. Translational Challenges in Cardiovascular Tissue Engineering. J. of Cardiovasc. Trans. Res. 10, 139–149 (2017). https://doi.org/10.1007/s12265-017-9728-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-017-9728-2

Keywords

Search

Navigation