POSS-PEG-NHS and GSH Cocrosslink DPAV to Prepare Anticalcification Bioprosthetic Scaffold With Enhanced Reendothelization, Anti-inflammation, and Anti-ROS.

Abstract

The morbidity and mortality associated with heart valve disease (HVD) are progressively increasing, making it a leading cause of the global cardiovascular disease burden. The most effective current treatment is valve replacement, primarily utilizing mechanical or bioprosthetic valves. However, mechanical valves necessitate lifelong anticoagulation therapy, which increases the risk of bleeding events, including cerebral hemorrhage. Bioprosthetic valves, predominantly fixed with glutaraldehyde (GLUT), suffer from poor durability, often deteriorating due to calcification within 10-15 years. To develop a superior artificial valve substitute, this work synthesized a macromolecular chemical agent, POSS-PEG-NHS, to co-crosslink decellularized porcine aortic valves (DPAV) with glutathione (GSH). Then the surface morphology and mechanical properties of the resulting material were investigated. The biocompatibility and hemocompatibility were further demonstrated through in vitro cell experiments. Subsequently, the comprehensive performance of the PPN-GSH-AV scaffold was evaluated in vivo using a subcutaneous implantation model in Sprague-Dawley (SD) rats. The results revealed predominant infiltration of M2 macrophages, reduced calcification formation, and enhanced re-endothelialization. In conclusion, this study demonstrates that modification with POSS-PEG-NHS and GSH significantly enhances the scaffold's mechanical properties, hemocompatibility, endothelialization, and anti-inflammatory, anti-ROS, and anticalcification abilities, showing considerable promise for clinical translation.