CO-loaded Hemoglobin/EGCG Nanoparticles Functional Coatings for Inflammation Modulation of Vascular Implants

Abstract During the implantation process of cardiovascular implants, vascular damage caused by inflammation occurs, and the inflammatory process is accompanied by oxidative stress. Currently, carbon monoxide (CO) has been demonstrated to exhibit various biological effects including vasodilatation, antithrombotic, anti-inflammatory, apoptosis-inducing and antiproliferative properties. In this study, hemoglobin/epigallocatechin-3-gallate (EGCG) core-shell nanoparticle-containing coating on stainless steel was prepared for CO loading and inflammation modulation. Inspired by strong coordination ability with CO, hemoglobin nanoparticle was first prepared and encapsulated into EGCG metal-phenolic networks. A polydopamine (PDA) linking layer was then coated on 316 stainless steel, and the hemoglobin/EGCG nanoparticles were loaded with the subsequent PDA deposition. It showed that the maximum release amount of CO by the coating was 17.0 nmol/cm2 in 48 h. In vitro evaluations conducted in a simulated inflammatory environment revealed that the coating, which released CO from hemoglobin/EGCG nanoparticles, effectively mitigated the lipopolysaccharide-induced inflammatory response in macrophages. Specifically, it decreased the expression of tumor necrosis factor-α, increased the expression of interleukin-10, suppressed the polarization of macrophages toward the M1 phenotype and reduced intracellular reactive oxygen species (ROS). Furthermore, under simulated oxidative stress conditions, the coating decreased the apoptosis of endothelial cells induced by oxidative stress and down-regulated intracellular ROS levels. In vivo implantation results further confirmed that the coating, with its hemoglobin/EGCG nanoparticles and CO release capabilities, reduced macrophage-mediated inflammatory responses and modulated the polarization phenotype of macrophages.