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

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 linking layer was then coated on 316 stainless steel, and the hemoglobin/EGCG nanoparticles was loaded with the subsequent polydopamine deposition. It showed that the maximum release amount of CO by the coating was 17.0 nmol/cm2 in 48 hours. In vitro evaluations conducted in a simulated inflammatory environment revealed that the coating, which released CO from hemoglobin/EGCG nanoparticles, effectively mitigated the LPS-induced inflammatory response in macrophages. Specifically, it decreased the expression of TNF-α, increased the expression of IL-10, suppressed the polarization of macrophages towards 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 downregulated 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.