Tissue-Guided Regenerated Valved Conduits: Long-Term Results of Porcine Decellularized alpha-Gal Negative Roots

The onset of calcification is still a major hurdle of structural valve deterioration of bioprosthetic valve. Durability, short- and long-term competency, host cell colonization leading to physiological ECM remodelling and growth potential are ideal requirements for any valve substitute. TRICOL decellularized porcine -Gal-negative aortic roots were used to replace RVOT in 4 vietnamese pigs (age 8–12 months) in a long term animal model up to 14 months (Group A). As a control group 2 animals had their RVOT resected and immediately reimplanted (Group B). Both groups underwent serial 2D and 3D echo evaluation prior to surgery and at 15 days, 1, 3, 6, 9, 12, 14 months. The explanted valved conduits were analysed by histology, immunohistochemistry and electron microscopy. Cell characterization and radioactive S35 uptake were also performed. Group A: echo imaging showed preserved leaflets motility over time as well as no signs of calcification. At 14 months range peak gradient: 15– 25 mm Hg; range mean gradient: 9–16 mm Hg. The implanted tissue revealed limited inflammatory infiltration with good endothelialization of luminal surfaces and cell engraftment with distribution similar to native condition. TEM and metabolic analysis revealed new formation of cell to cell junction, neural fibres, collagen and elastin synthesis as well as clear evidence of novel proteoglycans. Tissue positivity for stem cell markers and cell pattern of graft derived-primary cultures suggested cell repopulation originating from recipient bone marrow mesenchymal stem cells. Group B: valve analysis showed no fibrosis, no calcification with normal endothelial lining. At echo range mean gradient: 1.87–2.05 mm Hg; range peak gradient: 3.45– 4.05 mm Hg.