Abstract 13818: Polyoxazoline Modification of Bovine Pericardial Bioprosthetic Heart Valve Leaflets Mitigates Protein-Glycation Associated Structural Degeneration

Abstract

Introduction: Bioprosthetic heart valves (BHV) fabricated from glutaraldehyde treated bovine pericardium (BP) are widely used to treat heart valve disease. BHV dysfunction from structural valve degeneration (SVD) develops over time, often necessitating device replacement. SVD is associated with both calcification and the accumulation of advanced glycation end products (AGE) and serum proteins within BHV leaflets. Here, we introduce a new strategy for mitigating AGE-associated SVD by modifying BP with a poly(2-methyl-2-oxazoline) (POZ). Hypothesis: Attached POZ will prevent BP deterioration by mitigating serum protein and pro-inflammatory AGE uptake. Methods: Covalently modified BP-POZ was studied for its effects on serum albumin and AGE entry in vitro via a mass-uptake assay and immunostaining. Resistance of BP-POZ to oxidation was assessed in comparison to poly(ethylene glycol) (PEG). Macrophage studies assessed the inflammatory properties of BP-POZ. A juvenile rat subdermal model was used to study serum protein and AGE uptake and calcification within BP-POZ, with or without ethanol pretreatment. A heart valve pulse duplicator was used to assess the protective effects of BP-POZ on BHV hydrodynamics following accelerated glycation. Results: POZ mitigated the accumulation of serum albumin and AGE in vitro . After exposure to AGE and macrophages, POZ preserved BP collagen structure while TNFα levels remained at baseline. Under oxidation conditions, POZ retained its protective function, unlike PEG. In the rat model, POZ reduced BP AGE (p<0.001) and albumin (p<0.001) uptake. Ethanol pretreatment of BP-POZ was effective at reducing both AGE and calcification. POZ mitigated the hydrodynamic dysfunction of BHV exposed to accelerated glycation conditions (p<0.001). Conclusions: SVD due to AGE and serum proteins can be effectively mitigated through POZ modification, that does not interfere with ethanol pretreatment mitigation of BP calcification.