3D printed heart valve mediated nitric oxide sustained release reduced potential for calcification and inflammatory capacity

Abstract

Heart valve replacement have numerous problems, such as calcification, inflammation, and limited endothelialization. Herein, we used bio-degradable arginine-modified polylysine and oxidized hyaluronic acid as the substrate, expanding the advantages of rapid Schiff-base reaction of aldehydes and amino groups under physiological conditions to form dynamic acyl-hydrazone bonds. These were used to design dynamic adaptive hydrogels, and a polysaccharide/protein dual-network system that mimicked the extracellular matrix, realizing the excellent mechanical tunability and shear thinning properties of its hydrogel. The dual antibacterial mechanism effectively avoided the occurrence of infection-like inflammation after valve implantation. The hydrogel has great ability in promoting cellular proliferation, and can also promote cell migration through a potential cell recruitment mechanism. The hydrogel dynamically triggers and sustains NO release in vivo, removing highly expressed ROS in inflammatory site as needed. It further promotes angiogenesis, and provides targeted treatment for calcified aortic valve disease caused by oxidative stress signals. Furthermore, it exhibits exceptional anti-calcification properties and can enhance the upregulation of CD31 while suppressing the expression of IL-10 and TNF-α, thereby significantly promoting angiogenesis and reducing inflammation. Additionally, 3D printing technology enables the individualized customization of valves with diverse heterogeneous structures to achieve a high degree of biomimetic tissue.