Clinical and Experimental Studies of Structural Valve Degeneration of Bovine Jugular Vein Valves: Mitigation with Polyoxazoline Modification.

Bovine jugular vein (BJV) valves are widely used in congenital heart surgery but are limited in durability due to structural valve degeneration (SVD). Here, we examine mechanisms of BJV prosthesis failure and test BJV modification with poly-2-methyl-2-oxazoline (POZ), a polymer shown to inhibit protein and advanced glycation end-product (AGE) absorption. Clinical BJV valve explants (Melody valve, N = 13) underwent Von Kossa staining and immunohistochemistry (IHC) for AGE, carboxymethyllysine (CML), and serum albumin (SA). Collagen structure was analyzed using second-harmonic generation (SHG) imaging. Unmodified and POZ-modified BJV valved conduits underwent 5-week in vitro glycation incubation. Effective orifice area (EOA) and mean pressure gradient (MPG) were recorded weekly using a heart pulse duplicator system. Following incubation, leaflet thickness, IHC, and SHG analyses were performed. In vivo 28-day subcutaneous BJV leaflet implantations were performed in juvenile rats for IHC. Clinical BJV explants demonstrated AGE, CML, and SA infiltration. In vitro glycation induced leaflet thickening (control, 0.03 ± 0.01 vs non-modified, 0.23 ± 0.07 mm, p < 0.001), CML and SA infiltration, and collagen disruption (alignment coefficient: control, 0.76 ± 0.03 vs non-modified, 0.50 ± 0.19, p < 0.01). POZ-modified leaflets remained similar in thickness to unglycated controls. POZ modification reduced CML and SA accumulation and mitigated collagen malalignment. BJV conduits did not reveal clinically significant changes in MPG or EOA. In vivo studies verified POZ modification protected against microcalcification as well as AGE, CML, and SA deposition. BJV valves are subject to SVD-related mechanisms of AGE accumulation, serum protein infiltration, and collagen misalignment. POZ modification mitigates BJV leaflet thickening, AGE and protein infiltration, and collagen disruption.