Drug-Loaded Hybrid Tissue Engineered Heart Valve with Antithrombosis and Immunomodulation Performance

Porcine decellularized heart valve (DHV) leaflets were functionalized via a one-pot hybridization strategy to create a drug-loaded glycoprotein-like network tissue-engineered heart valve (OHSC-V) using oxidized hyaluronic acid (OHA) as a crosslinking backbone, phenylboronic-acid–grafted silk fibroin (SF-PBA), and curcumin (Cur). Relative to unmodified DHV and glutaraldehyde-fixed controls, hybridized valves exhibited increased surface roughness and markedly improved hydrophilicity, reduced platelet/whole-blood adhesion and protein adsorption, and improved dynamic hemocompatibility in an ex vivo rabbit blood circulation model. Endothelialization potential was enhanced, with higher HUVEC viability, spreading, and VEGF secretion on OHSC-V. Immunomodulatory performance was demonstrated by reduced macrophage pro-inflammatory cytokines (TNF-α, IL-1β) and increased anti-inflammatory signaling, supported by ROS-responsive Cur release. In a rat subcutaneous implantation model (up to 90 days), OHSC-V showed reduced inflammatory cell/macrophage recruitment and substantially lower calcification compared with glutaraldehyde-fixed leaflets, indicating a combined antithrombotic, pro-endothelial, immunomodulatory, and anticalcification surface engineering approach for next-generation TEHVs.