Nanoparticle Biofunctionalization of Bioprosthetic Heart Valves to Modulate Mechanisms of Structural Valve Deterioration

Bioprosthetic heart valves made from glutaraldehyde-fixed animal pericardium are widely used for valve replacement but are prone to early degeneration arising from the interplay of thrombosis, inflammation, and calcification. Current chemical treatments passivate the tissue surface but do not address these biological processes. This study introduces a plasma polymerized nanoparticle (PPN) platform that enables rapid, uniform coating of bioprosthetic pericardium and provides binding sites for active drug functionalization. Using PPNs, we immobilized the anticoagulant apixaban, the selective NLRP3-inflammasome inhibitor MCC950, or the anticalcification compound phytic acid directly onto valve tissue. These functionalized coatings reduced thrombosis in vitro and limited fibrosis and calcification in a 28-day rat subcutaneous model, demonstrating the capacity of PPNs to conjugate different small molecules to target multiple mechanisms of valve deterioration. Importantly, PPN coatings did not alter leaflet mechanics or hemodynamic performance when applied to a commercial transcatheter valve. This versatile coating platform represents an important advance in bioprosthetic valve technology with significant implications for their performance.