The PEDIAVALVE project - tissue-engineered pulmonary valves for paediatric valvular replacement.

Current paediatric options for pulmonary heart valve (PHV) substitutes are imperfect, requiring numerous reinterventions until maturity. Substitutes with a diameter under 15 mm have a limited service life, underscoring the critical need for small-diameter valves. To address this need, we obtained and tested decellularized, DNA-depleted, small-diameter valvular substitutes using tissue-engineered lamb PHVs. Lamb PHVs were subjected to a decellularization perfusion protocol, yielding a 3D extracellular matrix (ECM)- derived acellular scaffold. Sterility, residual nuclei (histology) and DNA content were assessed. Hemodynamic performance was assessed in a dedicated heart valve bioreactor, compared with freshly harvested PHV. Cytocompatibility was assessed using fibroblasts and endothelial cells, and the ex vivo surgical implantation feasibility was evaluated. Decellularization validation revealed preserved ECM without cell nuclei, and over 90% DNA reduction. In vitro hemodynamic assessment showed physiological behaviour with complete opening and no evidence of regurgitation or stenosis; geometric and Doppler parameters were comparable to fresh valves. Cells remained viable at 3, 7 and 14 days, and ex vivo implantations were successful, with adequate suturing. Decellularization of small ovine PHV is feasible, yielding cytocompatible scaffolds with good hemodynamics and surgical handling. Although initial results are promising, further quantitative characterization and in vivo validation are needed before clinical translation.