Advancing Heart Valve Replacement: Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue Banks
Jose Ignacio Rodríguez Martínez,1,2,* Cristina Castells-Sala,1,2,* Ana Rita Baptista Piteira,1,2 Giulia Montagner,3 Diletta Trojan,3 Pablo Martinez-Legazpi,4,5 Alejandra Acosta Ocampo,5,6 Maria Eugenia Fernández-Santos,5,6 Javier Bermejo,5– 7 Ramadan Jashari,8 Maria Luisa Pérez,1,9 E...
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Dove Medical Press
2025-02-01
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| Series: | Therapeutics and Clinical Risk Management |
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| author | Rodríguez Martínez JI Castells-Sala C Piteira AR Montagner G Trojan D Martinez-Legazpi P Acosta Ocampo A Fernández-Santos ME Bermejo J Jashari R Pérez ML Agustí E Tabera J Vilarrodona A |
| author_facet | Rodríguez Martínez JI Castells-Sala C Piteira AR Montagner G Trojan D Martinez-Legazpi P Acosta Ocampo A Fernández-Santos ME Bermejo J Jashari R Pérez ML Agustí E Tabera J Vilarrodona A |
| author_sort | Rodríguez Martínez JI |
| collection | DOAJ |
| description | Jose Ignacio Rodríguez Martínez,1,2,* Cristina Castells-Sala,1,2,* Ana Rita Baptista Piteira,1,2 Giulia Montagner,3 Diletta Trojan,3 Pablo Martinez-Legazpi,4,5 Alejandra Acosta Ocampo,5,6 Maria Eugenia Fernández-Santos,5,6 Javier Bermejo,5– 7 Ramadan Jashari,8 Maria Luisa Pérez,1,9 Elba Agustí,1,9 Jaime Tabera,1,2 Anna Vilarrodona1,9 1Barcelona Tissue Bank, Banc de Sang i Teixits (BST), Barcelona, Spain; 2Biomedical Research Institute (IIB-Sant Pau; SGR1113), Barcelona, Spain; 3Fondazione Banca dei Tessuti del Veneto, Treviso, Italy; 4Department of Mathematical Physics and Fluids, Universidad Nacional de Educación a Distancia, UNED, Madrid, Spain; 5Centre for Biomedical Research in Cardiovascular Disease Network (CIBER-CV) and Red de Investigación Cooperativa Orientada a Resultados En Salud (RICORS) TERAV, from the Instituto de Salud Carlos III, Madrid, Spain; 6Department of Cardiology, Hospital General Universitario Gregorio Marañón, Gregorio Marañón Health Research Institute (Iisgm), Madrid, Spain; 7Facultad de Medicina, Universidad Complutense, Madrid, Spain; 8European Homograft Bank (EHB) Cliniques Universitaires, Saint-Luc, Bruxelles; 9Vall Hebron Institute of Research (VHIR), Barcelona, Spain*These authors contributed equally to this workCorrespondence: Cristina Castells-Sala, Barcelona Tissue Bank (BTB), Banc de Sang i Teixits (BST, GenCAT), Passeig Taulat 116, Barcelona, E-08005, Spain, Tel +34 935573500, Email ccastells@bst.catPurpose: 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. Keywords: Pulmonary valve, decellularization, extracellular matrix, risk assessment, EuroGTP II |
| format | Article |
| id | doaj-art-2cfc40f11735475699696050d7dfc87b |
| institution | DOAJ |
| issn | 1178-203X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Therapeutics and Clinical Risk Management |
| spelling | doaj-art-2cfc40f11735475699696050d7dfc87b2025-08-20T03:12:04ZengDove Medical PressTherapeutics and Clinical Risk Management1178-203X2025-02-01Volume 21209228100566Advancing Heart Valve Replacement: Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue BanksRodríguez Martínez JICastells-Sala CPiteira ARMontagner GTrojan DMartinez-Legazpi PAcosta Ocampo AFernández-Santos MEBermejo JJashari RPérez MLAgustí ETabera JVilarrodona AJose Ignacio Rodríguez Martínez,1,2,* Cristina Castells-Sala,1,2,* Ana Rita Baptista Piteira,1,2 Giulia Montagner,3 Diletta Trojan,3 Pablo Martinez-Legazpi,4,5 Alejandra Acosta Ocampo,5,6 Maria Eugenia Fernández-Santos,5,6 Javier Bermejo,5– 7 Ramadan Jashari,8 Maria Luisa Pérez,1,9 Elba Agustí,1,9 Jaime Tabera,1,2 Anna Vilarrodona1,9 1Barcelona Tissue Bank, Banc de Sang i Teixits (BST), Barcelona, Spain; 2Biomedical Research Institute (IIB-Sant Pau; SGR1113), Barcelona, Spain; 3Fondazione Banca dei Tessuti del Veneto, Treviso, Italy; 4Department of Mathematical Physics and Fluids, Universidad Nacional de Educación a Distancia, UNED, Madrid, Spain; 5Centre for Biomedical Research in Cardiovascular Disease Network (CIBER-CV) and Red de Investigación Cooperativa Orientada a Resultados En Salud (RICORS) TERAV, from the Instituto de Salud Carlos III, Madrid, Spain; 6Department of Cardiology, Hospital General Universitario Gregorio Marañón, Gregorio Marañón Health Research Institute (Iisgm), Madrid, Spain; 7Facultad de Medicina, Universidad Complutense, Madrid, Spain; 8European Homograft Bank (EHB) Cliniques Universitaires, Saint-Luc, Bruxelles; 9Vall Hebron Institute of Research (VHIR), Barcelona, Spain*These authors contributed equally to this workCorrespondence: Cristina Castells-Sala, Barcelona Tissue Bank (BTB), Banc de Sang i Teixits (BST, GenCAT), Passeig Taulat 116, Barcelona, E-08005, Spain, Tel +34 935573500, Email ccastells@bst.catPurpose: 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. Keywords: Pulmonary valve, decellularization, extracellular matrix, risk assessment, EuroGTP IIhttps://www.dovepress.com/advancing-heart-valve-replacement-risk-mitigation-of-decellularized-pu-peer-reviewed-fulltext-article-TCRMpulmonary valvedecellularizationextracellular matrixrisk assessmenteurogtp ii |
| spellingShingle | Rodríguez Martínez JI Castells-Sala C Piteira AR Montagner G Trojan D Martinez-Legazpi P Acosta Ocampo A Fernández-Santos ME Bermejo J Jashari R Pérez ML Agustí E Tabera J Vilarrodona A Advancing Heart Valve Replacement: Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue Banks Therapeutics and Clinical Risk Management pulmonary valve decellularization extracellular matrix risk assessment eurogtp ii |
| title | Advancing Heart Valve Replacement: Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue Banks |
| title_full | Advancing Heart Valve Replacement: Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue Banks |
| title_fullStr | Advancing Heart Valve Replacement: Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue Banks |
| title_full_unstemmed | Advancing Heart Valve Replacement: Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue Banks |
| title_short | Advancing Heart Valve Replacement: Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue Banks |
| title_sort | advancing heart valve replacement risk mitigation of decellularized pulmonary valve preparation for its implementation in public tissue banks |
| topic | pulmonary valve decellularization extracellular matrix risk assessment eurogtp ii |
| url | https://www.dovepress.com/advancing-heart-valve-replacement-risk-mitigation-of-decellularized-pu-peer-reviewed-fulltext-article-TCRM |
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