A Robust Biprotein Stabilized Pericardium Valve Material Priming Resistance to Calcification

In the absence of effective therapeutics, valve replacement remains the sole intervention for severe calcific aortic valve disease (CAVD), which impacts 26% of adults aged 65 and even 50% of adults aged 85. Pericardium-based bioprosthetic heart valves benefit from marginating anticoagulation. Still, they face recalcification due to residual aldehydes and inadequate elastin stabilization from the glutaraldehyde cross-linking process, posing a significant clinical challenge. Herein, we propose a biprotein stabilized pericardium material (CHPP) that involves both collagen and elastin cross-linked by procyanidins (PC) with the assistance of 3,4-hydroxyphenylpropionic acid (HPA), which conferred improved stability to pericardium even under enzymatic attack, increasing biocompatibility and minimizing platelet absorption, and taken together significantly contributed to resisting calcification. Further, <i>in vivo</i> studies demonstrated the preservation of the structure of CHPP, and more importantly, CHPP can prevent surrounding tissue infiltration and immune responses, reducing the infiltration of macrophages and T cells, along with their cascading inflammatory processes and establishing an immune-privileged microenvironment that further enhances its anticalcification capacity. These advancements offer an enhancing approach using procyanidins to significantly stabilize biprotein components within the pericardium, thereby creating immune tolerance against calcification and providing an alternative for robust generation of valve materials.