Advancing Heart Valve Replacement : Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue Banks
Rodríguez Martínez, José Ignacio (Institut de Recerca Sant Pau)
Castells-Sala, Cristina (Institut de Recerca Sant Pau)
Baptista Piteira, Ana Rita (Institut de Recerca Sant Pau)
Montagner, G. (Fondazione Banca dei Tessuti del Veneto)
Trojan, D. (Fondazione Banca dei Tessuti del Veneto)
Martinez-Legazpi, P. (Instituto de Salud Carlos III)
Ocampo, A.A. (Hospital General Universitario Gregorio Marañón)
Fernández-Santos, M.E. (Hospital General Universitario Gregorio Marañón)
Bermejo, J. (Universidad Complutense de Madrid)
Jashari, R. (European Homograft Bank(EHB) Cliniques Universitaires. Saint-Luc)
Pérez, Maria Luisa (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Agustí, Elba (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Tabera, Jaime (Institut de Recerca Sant Pau)
Vilarrodona, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2025
Abstract:	Purpose: Cryopreserved homografts for valve replacement surgeries face a major problem regarding their durability after implantation and decellularized pulmonary heart valves have raised as potential new generation substitute for these surgeries. The present study aims to document the work performed for the safe implementation in public tissue banks of a new decellularization method for human pulmonary heart valves, based on previous risk evaluation. Methods: After assessing new preparation method associated risks, using EuroGTP-II methodologies, an extensive array of in vitro studies were defined to validate the new technique, mitigate the risks and provide quality and safety data. Results: Initial evaluation of risks using EuroGTP II tool, showed Final Risk Score of 23 (high risk), and four studies were devised to mitigate identified risks: (i) tissue structure integrity; (ii) cell content; (iii) microbiological safety; and (iv) cytotoxicity evaluation in final tissue preparation. Protein quantification, mechanical properties, and histological evaluation indicated no tissue damage, reducing implant failure probability, while cellular content removal demonstrated a 99% DNA removal and microbiological control ensured contamination absence. Moreover, in vitro results showed no cytotoxicity. Risk re-evaluation indicated a risk reduction to moderate risk (Final Risk Score = 10), suggesting that further evidence for safe clinical use would be needed at pre-clinical in vivo evaluation to mitigate remaining risks. Conclusions: The studies performed and reviewed bibliography were able to significantly reduce the original level of risk associated with the clinical application of this homograft's preparation. However, additional in vivo studies and tissue stability tests are still necessary to address the remaining risks associated with reagents' effect on extracellular matrix and storage conditions, which could influence implant failure, before the clinical evaluation procedures can be implemented to determine the efficacy and safety of the new decellularized heart valves.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	EuroGTP II ; Pulmonary valve ; Decellularization ; Extracellular matrix ; Risk assessment
Published in:	Therapeutics and Clinical Risk Management, Vol. 21 (2025) , p. 209-228, ISSN 1178-203X

DOI: 10.2147/TCRM.S486508
PMID: 40035073

20 p, 10.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles