In vivo evaluation of an in-body, tissue-engineered, completely autologous valved conduit (biovalve type VI) as an aortic valve in a goat model
- 415 Downloads
Using simple, safe, and economical in-body tissue engineering, autologous valved conduits (biovalves) with the sinus of Valsalva and without any artificial support materials were developed in animal recipients’ bodies. In this study, the feasibility of the biovalve as an aortic valve was evaluated in a goat model. Biovalves were prepared by 2-month embedding of the molds, assembled using two types of specially designed plastic rods, in the dorsal subcutaneous spaces of goats. One rod had three projections, resembling the protrusions of the sinus of Valsalva. Completely autologous connective tissue biovalves (type VI) with three leaflets in the inner side of the conduit with the sinus of Valsalva were obtained after removing the molds from both terminals of the harvested implants with complete encapsulation. The biovalve leaflets had appropriate strength and elastic characteristics similar to those of native aortic valves; thus, a robust conduit was formed. Tight valvular coaptation and a sufficient open orifice area were observed in vitro. Biovalves (n = 3) were implanted in the specially designed apico-aortic bypass for 2 months as a pilot study. Postoperative echocardiography showed smooth movement of the leaflets with little regurgitation under systemic circulation (2.6 ± 1.1 l/min). α-SMA–positive cells appeared significantly with rich angiogenesis in the conduit and expanded toward the leaflet tip. At the sinus portions, marked elastic fibers were formed. The luminal surface was covered with thin pseudointima without thrombus formation. Completely autologous biovalves with robust and elastic characteristics satisfied the higher requirements of the systemic circulation in goats for 2 months with the potential for valvular tissue regeneration.
KeywordsIn vivo tissue engineering Heart valve Autologous tissue Aortic valve Systemic circulation
The authors thank Ms. Manami Sone, Mr. Yuji Shimakawa, and Dr. Yue-Min Zhou for their participation in this study. This study was funded in part by a Grant-in-Aid for Scientific Research (B19390368, B21360123) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
- 2.Shin’oka T, Ma PX, Shum-Tim D, Breuer CK, Cusick RA, Zund G, Langer R, Vacanti JP, Mayer JE. Tissue-engineered heart valves. Autologous valve leaflet replacement study in a lamb model. Circulation. 1996;94:164–8.Google Scholar
- 3.Dohmen PM, Ozaki S, Nitsch R, Yperman J, Flameng W, Konertz W. A tissue engineered heart valve implanted in a juvenile sheep model. Med Sci Monit. 2003;9:97–104.Google Scholar
- 5.Baraki H, Tudorache I, Braun M, Höffler K, Görler A, Lichtenberg A, Bara C, Calistru A, Brandes G, Hewicker-Trautwein M, Hilfiker A, Haverich A, Cebotari S. Orthotopic replacement of the aortic valve with decellularized allograft in a sheep model. Biomaterials. 2009;30:6240–6.PubMedCrossRefGoogle Scholar
- 13.Yamanami M, Yahata Y, Uechi M, Fujiwara M, Ishibashi-Ueda H, Kanda K, Watanabe T, Tajikawa T, Ohba K, Yaku H, Nakayama Y. Development of a completely autologous valved conduit with the sinus of valsalva using in-body tissue architecture technology: a pilot study in pulmonary valve replacement in a beagle model. Circulation. 2010;122:S100–6.PubMedCrossRefGoogle Scholar
- 15.Conconi MT, Rocco F, Spinazzi R, Tommasini M, Valfrè C, Busetto R, Polesel E, Albertin G, Dei Tos A, Iacopetti I, Cecchetto A, Zussa C, Grigioni M, Parnigotto PP, Nussdorfer GG. Biological fate of tissue-engineered porcine valvular conduits xenotransplanted in the sheep thoracic aorta. Int J Mol Med. 2004;14:1043–8.PubMedGoogle Scholar
- 17.Van Nooten G, Somers P, Cornelissen M, Bouchez S, Gasthuys F, Cox E, Sparks L, Narine K. Acellilar porcine and kangaroo aortic valve scaffolds show more intense immune-mediated calcification than cross-linked Toronto SPV valves in the sheep model. Interact Cardiovasc Thorac Surg. 2006;5:544–9.PubMedCrossRefGoogle Scholar