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

Abstract

High thrombogenicity and shortened lifespan have limited the application of mechanical valves and bioprosthetic valves, respectively. Tissue engineering heart valve (TEHV) holds significant potential as a favorable prosthetic valve to overcome the limitations of the current prosthetic valves, featuring the capabilities of self-pairing and adaptive remodeling. However, TEHVs, mainly fabricated from decellularized xenogeneic heart valves (DHV), still have challenges such as thrombosis, inferior endothelialization, and immune responses. Herein, a drug-loaded glycoprotein-like network hybrid TEHV (OHSC-V) was engineered through the one-pot hybridization of DHV, oxidized HA (OHA), phenylboronic acid grafted silk fibroin (SF-PBA), and curcumin (Cur), where OHA served as a biocompatible backbone to cross-link the DHV and the conjugate of SF-PBA and Cur. With the introduction of the multifunctional drug-loaded glycoprotein-like network, OHSC-V not only effectively inhibited the adsorption of plasma proteins, blood cells, platelets, and thrombosis but also facilitated the endothelialization of TEHV. Furthermore, the OHSC-V eliminated the reactive oxygen species and responsively released Cur to modulate the immune responses. Moreover, the calcification degree of hybrid TEHVs was markedly lower than that of glutaraldehyde cross-linked DHV after 90 days of implantation. Overall, OHSC-V demonstrated enhanced performance of antithrombosis, endothelialization, immunomodulation, and anticalcification, showcasing the further potential for application exploration.