Vitamin B6 Modification of Bovine Pericardial Bioprosthetic Heart Valve Leaflets Promotes Blood Outgrowth Endothelial Cell Adhesion

Bioprosthetic heart valves (BHV), typically fabricated from glutaraldehyde-fixed bovine pericardium (BP), are the most common type of replacement for patients with severe heart valve disease. Despite being preferred, BHV are limited in durability due to structural valve degeneration (SVD), which occurs due to leaflet calcification and non-calcific mechanisms including advanced glycation end product (AGE) accumulation and serum protein infiltration. Another limitation of BHV is characteristically they do not endothelialize, even after years of implantation. Previously we showed pretreating BP with Pyridoxamine (PYR), a vitamer of vitamin B6, effectively mitigated AGE accumulation in vitro and in vivo. The present studies investigated the effect of PYR pretreated BHV on endothelial cell-material interactions, using bone marrow origin human blood outgrowth endothelial cells (BOEC) as a model cell type; the hypothesis was PYR pretreatment would provide a more favorable surface for endothelialization compared to glut-fixed BP. Static studies compared untreated BP versus PYR-BP to examine the effect on cell adhesion; PYR-BP had significantly more BOEC adhered than untreated BP measured by Alamar blue assays. PYR pretreatment under non-AGE and model AGE conditions were also investigated via static and high shear studies. PYR pretreated collagen coated-glutaraldehyde fixed slides significantly increased BOEC attachment over time under AGE and non-AGE conditions. Under arterial shear levels, PYR pretreatment increased BOEC retention compared to untreated slides under non-AGE and AGE conditions. In conclusion, PYR pretreated BP or model, thin-layer collagen surfaces promote endothelial cell attachment and reduced cytotoxicity under static and shear conditions, with or without AGE presence.