Tubular Heart Valves from Decellularized Engineered Tissue
- 891 Downloads
A novel tissue-engineered heart valve (TEHV) was fabricated from a decellularized tissue tube mounted on a frame with three struts, which upon back-pressure cause the tube to collapse into three coapting “leaflets.” The tissue was completely biological, fabricated from ovine fibroblasts dispersed within a fibrin gel, compacted into a circumferentially aligned tube on a mandrel, and matured using a bioreactor system that applied cyclic distension. Following decellularization, the resulting tissue possessed tensile mechanical properties, mechanical anisotropy, and collagen content that were comparable to native pulmonary valve leaflets. When mounted on a custom frame and tested within a pulse duplicator system, the tubular TEHV displayed excellent function under both aortic and pulmonary conditions, with minimal regurgitant fractions and transvalvular pressure gradients at peak systole, as well as well as effective orifice areas exceeding those of current commercially available valve replacements. Short-term fatigue testing of one million cycles with pulmonary pressure gradients was conducted without significant change in mechanical properties and no observable macroscopic tissue deterioration. This study presents an attractive potential alternative to current tissue valve replacements due to its avoidance of chemical fixation and utilization of a tissue conducive to recellularization by host cell infiltration.
KeywordsHeart valve Tissue engineering Pulse duplicator Decellularization
Authors will like to thank Naomi Ferguson, and Jillian Schmidt for technical assistance and Dave Hultman Design for machining the custom pulse duplicator system, bioreactor manifold and valve frames. The funding for the work was provided by NIH R01 HL107572 (to RTT).
- 5.Dahl, S. L., A. P. Kypson, J. H. Lawson, J. L. Blum, J. T. Strader, Y. Li, R. J. Manson, W. E. Tente, L. DiBernardo, M. T. Hensley, R. Carter, T. P. Williams, H. L. Prichard, M. S. Dey, K. G. Begelman, and L. E. Niklason. Readily available tissue-engineered vascular grafts. Sci. Transl. Med. 3:68ra69, 2011.CrossRefGoogle Scholar
- 8.Emmert, M. Y., B. Weber, L. Behr, T. Frauenfelder, C. E. Brokopp, J. Grunenfelder, V. Falk, and S. P. Hoerstrup. Transapical aortic implantation of autologous marrow stromal cell-based tissue-engineered heart valves: first experiences in the systemic circulation. JACC. Cardiovasc. Interv. 4:822–823, 2011.CrossRefPubMedGoogle Scholar
- 10.Flanagan, T. C., J. S. Sachweh, J. Frese, H. Schnoring, N. Gronloh, S. Koch, R. H. Tolba, T. Schmitz-Rode, and S. Jockenhoevel. In vivo remodeling and structural characterization of fibrin-based tissue-engineered heart valves in the adult sheep model. Tissue Eng. A 15:2965–2976, 2009.CrossRefGoogle Scholar
- 13.Hoerstrup, S. P., R. Sodian, S. Daebritz, J. Wang, E. A. Bacha, D. P. Martin, A. M. Moran, K. J. Guleserian, J. S. Sperling, S. Kaushal, J. P. Vacanti, F. J. Schoen, and J. E. Mayer Jr. Functional living trileaflet heart valves grown in vitro. Circulation 102:III44–III49, 2000.CrossRefPubMedGoogle Scholar
- 16.Nakayama, Y., Y. Yahata, M. Yamanami, T. Tajikawa, K. Ohba, K. Kanda, and H. Yaku. A completely autologous valved conduit prepared in the open form of trileaflets (type VI biovalve): mold design and valve function in vitro. J. Biomed. Mater. Res. B Appl. Biomater. 99:135–141, 2011.PubMedGoogle Scholar
- 21.Schmidt, D., P. E. Dijkman, A. Driessen-Mol, R. Stenger, C. Mariani, A. Puolakka, M. Rissanen, T. Deichmann, B. Odermatt, B. Weber, M. Y. Emmert, G. Zund, F. P. Baaijens, and S. P. Hoerstrup. Minimally-invasive implantation of living tissue engineered heart valves: a comprehensive approach from autologous vascular cells to stem cells. J. Am. Coll. Cardiol. 56:510–520, 2010.CrossRefPubMedGoogle Scholar
- 29.Syedain, Z. H., L. Meier, M. Lahti, S. Johnson, and R. T. Tranquillo. Implantation of completely biological, aligned engineered arteries pre-made from allogeneic fibroblasts in a sheep model. 2013 (submitted).Google Scholar
- 34.Weber, B., J. Scherman, M. Y. Emmert, J. Gruenenfelder, R. Verbeek, M. Bracher, M. Black, J. Kortsmit, T. Franz, R. Schoenauer, L. Baumgartner, C. Brokopp, I. Agarkova, P. Wolint, G. Zund, V. Falk, P. Zilla, and S. P. Hoerstrup. Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates. Eur. Heart J. 32:2830–2840, 2011.CrossRefPubMedGoogle Scholar