Abstract

Immunogenicity of human allografts leads to gradual valve degeneration. Pulmonal cell-free valvular scaffolds obtained by methods of tissue engineering have proved to induce in-vivo guided tissue regeneration and represent a promising valve substitute especially for children. Here we describe the successful orthotopic implantation of decellularized aortic valves in the systemic circulation in sheep. Allogenic detergent decellularized (0.5% sodium deoxycholate/0.5% SDS) aortic valve (AV) conduits (n = 12) were implanted orthotopically as root replacement in lambs (35–45 kg). Fresh native AV conduits served as controls (n = 6). After three and nine months follow-up the valves were investigated for functionality by echocardiography, for morphology and histological appearance. Decellularization resulted in complete loss of cells in AV wall, cusp and myocardial cuff, no influence on scaffold microarchitecture was observed. During 9 months follow-up no signs of conduit dilatation, aortic stenosis (transvalvular gradient max. 6.1 ± 5.1mmHg) or reduction of cusp mobility were observed in the decellularized group. Regurgitation in these valves was trivial in all cases. The grafts showed no histological signs of rejection and partial repopulation of the valvular scaffolds with autologous cells. In contrast, control animals developed mild to severe AV insufficiency. Histological investigation revealed significant calcific degeneration and massive rejection of these valves. Decellularized AV conduits may represent a durable AV substitute resistant to high systemic pressure. Furthermore, cell-removal prevents the allograft valve from immunologic deterioration and early graft degeneration.

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