In the last two decades, clinical demand of allogeneic valve substitutes exceeded cryobank supply of human heart valves, despite their long-term failure due to host-versus-graft immune responses. Previously, TRICOL-decellularized porcine aortic valve allografts (TDVs) implanted in Vietnamese pigs showed functional capacity besides being permissive of in-vivo spontaneous repopulation by host cells and tissue remodelling. Here, using the same animal model, TDVs were compared with others additionally subjected to cryopreservation/thawing (TDCVs). Animal use for experimental purposes was authorized by the Italian Ministry of Health (27/08 C16 project), according to D.L. n. 116, art. 12, January 27, 1992. All procedures on animals were performed in compliance with ISO 10993-1, ISO 10993-2, and UNI EN ISO 5840 standards. For both allograft types, almost complete re-endothelialization was observed as well as repopulation by cells resembling fibroblasts, myofibroblasts, and smooth muscle cells, some of which exhibited typical canals of collagen fibrillogenesis and elastogenesis-related features revealing tissue remodelling occurrence. Moreover, neo-vascularization and re-innervation involved aorta medial and adventitial tunicae. Altered regions were also apparent, which showed tissue lesions including calcification, affecting TDCVs more severely than TDVs. In conclusion, cryopreservation was found to limit the favourable outcomes characterizing TDVs, although hemodynamic performance and permissivity to cell repopulation and tissue renewal were not compromised. Thus, these preclinical data suggest potential feasibility of cryobank-derived hemodynamically functional and self-regenerating allogeneic valve substitutes, once optimization of pre-implantation procedures or their mutual compatibility will be accomplished.

Cryopreservation of bioengineered, decellularized aortic valves does not compromise their propensity to repopulation by host cells and tissue remodelling. Good and less good outcomes

BONETTI, Antonella;ORTOLANI, Fulvia
2015

Abstract

In the last two decades, clinical demand of allogeneic valve substitutes exceeded cryobank supply of human heart valves, despite their long-term failure due to host-versus-graft immune responses. Previously, TRICOL-decellularized porcine aortic valve allografts (TDVs) implanted in Vietnamese pigs showed functional capacity besides being permissive of in-vivo spontaneous repopulation by host cells and tissue remodelling. Here, using the same animal model, TDVs were compared with others additionally subjected to cryopreservation/thawing (TDCVs). Animal use for experimental purposes was authorized by the Italian Ministry of Health (27/08 C16 project), according to D.L. n. 116, art. 12, January 27, 1992. All procedures on animals were performed in compliance with ISO 10993-1, ISO 10993-2, and UNI EN ISO 5840 standards. For both allograft types, almost complete re-endothelialization was observed as well as repopulation by cells resembling fibroblasts, myofibroblasts, and smooth muscle cells, some of which exhibited typical canals of collagen fibrillogenesis and elastogenesis-related features revealing tissue remodelling occurrence. Moreover, neo-vascularization and re-innervation involved aorta medial and adventitial tunicae. Altered regions were also apparent, which showed tissue lesions including calcification, affecting TDCVs more severely than TDVs. In conclusion, cryopreservation was found to limit the favourable outcomes characterizing TDVs, although hemodynamic performance and permissivity to cell repopulation and tissue renewal were not compromised. Thus, these preclinical data suggest potential feasibility of cryobank-derived hemodynamically functional and self-regenerating allogeneic valve substitutes, once optimization of pre-implantation procedures or their mutual compatibility will be accomplished.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11390/1107082
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