Advancing Heart Valve Replacement: Risk Mitigation of Decellularized Pulmonary Valve Preparation for Its Implementation in Public Tissue Banks.

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.