Wu Sui, Dong Ruichen, Xie Yinhong, Chen Wenhao, Liu Wei, Weng Yajun
Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu 610031, China.
School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Regen Biomater. 2024 Dec 20;12:rbae148. doi: 10.1093/rb/rbae148. eCollection 2025.
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/cm in 48 h. 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. 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.
在心血管植入物的植入过程中,会发生由炎症引起的血管损伤,并且炎症过程伴随着氧化应激。目前,一氧化碳(CO)已被证明具有多种生物学效应,包括血管舒张、抗血栓形成、抗炎、诱导凋亡和抗增殖特性。在本研究中,制备了含血红蛋白/表没食子儿茶素-3-没食子酸酯(EGCG)核壳纳米颗粒的不锈钢涂层,用于CO负载和炎症调节。受与CO的强配位能力启发,首先制备血红蛋白纳米颗粒并将其封装到EGCG金属酚网络中。然后在316不锈钢上涂覆一层聚多巴胺(PDA)连接层,并通过随后的PDA沉积负载血红蛋白/EGCG纳米颗粒。结果表明,该涂层在48小时内CO的最大释放量为17.0 nmol/cm 。在模拟炎症环境中进行的评估表明,从血红蛋白/EGCG纳米颗粒释放CO的涂层有效减轻了脂多糖诱导的巨噬细胞炎症反应。具体而言,它降低了肿瘤坏死因子-α的表达,增加了白细胞介素-10的表达,抑制了巨噬细胞向M1表型的极化,并降低了细胞内活性氧(ROS)水平。此外,在模拟氧化应激条件下,该涂层降低了氧化应激诱导的内皮细胞凋亡,并下调了细胞内ROS水平。植入结果进一步证实,具有血红蛋白/EGCG纳米颗粒和CO释放能力的涂层减少了巨噬细胞介导的炎症反应,并调节了巨噬细胞的极化表型。