Polyaspartic Acid-Doped With Robust Polymerized Hydrogel Armor Enhances Anti-Calcification of Decellularized Porcine Heart Valves.

Abstract

Calcification remains a critical barrier to the long-term durability of glutaraldehyde-fixed decellularized bioprosthetic heart valves, despite their favorable biocompatibility and reduced thrombogenicity. Here, we identify polyaspartic acid (PASP) as a potent inhibitor of valve calcification. PASP modulates key pathological pathways by suppressing osteogenic differentiation (e.g., BMP2 and RUNX2), enhancing anti-calcification regulators (e.g., OPN and MGP), and reducing apoptosis in vitro. In addition, its calcium-chelating capability effectively inhibits dystrophic mineral deposition within the extracellular matrix in vivo. To achieve sustained and localized delivery of PASP, we developed a robust hydrogel coating on the valve surface via a surface-catalyzed free-radical polymerization reaction combined with UV-mediated secondary photocrosslinking. This functional coating enables stable encapsulation and controlled release of PASP while preserving mechanical integrity and long-term structural stability, thereby providing durable anti-calcification performance. Collectively, our findings establish a bioinspired and clinically relevant strategy for preserving the structural and functional integrity of bioprosthetic heart valves and provide a generalizable platform for the design of anti-calcification biomaterials for cardiovascular implants.