In vivo functional performance and structural maturation of decellularised allogenic aortic valves in the subcoronary position

Abstract

Objective: Successful animal and clinical implantation of decellularised heart valves has been performed in the pulmonary position. Comparable results have not yet been achieved for the aortic position with the high haemodynamic demands of the systemic circulation and the challenging implantation procedure.

Methods: Allogenic aortic valves (n=10) were decellularised using detergents (decellularised aortic valves (dAoVs)). Five prostheses were analysed for decellularisation quality and scaffold preservation. Five valves were orthotopically implanted in juvenile sheep in a subcoronary technique. After 5 months, echocardiography, immunohistology, histology, electron microscopy and western blot (WB) were used for analysis.

Results: All animals survived the follow-up with increased body weight (38.8 ± 2.8kg vs 56.0 ± 2.6kg, p<0.001). After implantation, three dAoVs showed negligible and two others minor insufficiency (I), which remained unchanged at explantation. Effective orifice area increased slightly (1.1 ± 0.2cm(2) vs 1.6 ± 0.3cm(2), p=0.051). Explanted dAoVs (n=4) showed excellent macroscopy with minor soft-tissue nodules observed at the free cusp margins of only one dAoV. No valve showed any signs of thrombosis or calcification. On microscopic evaluation, the cusp architecture was preserved with an almost complete endothelial repopulation as confirmed by vimentin(+)/von Willebrand factor (vWF(+))-staining, WB of endothelial markers (eNOS/vWF) and scanning electron microscopy (SEM). Partial interstitial reseeding with vimentin(+)/alpha-smooth muscle (αsm(+))-cells was noted. Quantitative measurement of collagen-IV, collagen-I, laminin and elastin (WB) demonstrated preserved scaffold composition as compared to native tissue.

Conclusion: The dAoVs showed excellent functional outcome at 5 months in a subcoronary model of juvenile sheep. Advanced endothelial and nascent interstitial repopulation, with preserved structural integrity under the high-shear-stress milieu of the aortic valve, encourage further long-term studies.