Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Toxicol Appl Pharmacol. 2013 Nov 1;272(3):703-12. doi: 10.1016/j.taap.2013.07.023. Epub 2013 Aug 7.
In previous work, we developed novel antibacterial hybrid coatings based on dextran containing dispersed Ag NPs (~5 nm, DEX-Ag) aimed to offer dual protection against two of the most common complications associated with implant surgery, infections and rejection of the implant. However, their blood-material interactions are unknown. In this study, we assess the hemocompatibility and biocompatibility of DEX-Ag using fresh blood and two cell lines of the immune system, monocytes (THP-1 cells) and macrophages (PMA-stimulated THP-1 cells). Glass, polyurethane (PU) and bare dextran (DEX) were used as reference surfaces. PU, DEX and DEX-Ag exhibited non-hemolytic properties. Relative to glass (100%), platelet attachment on PU, DEX and DEX-Ag was 15%, 10% and 34%, respectively. Further, we assessed cell morphology and viability, pro-inflammatory cytokines expression (TNF-α and IL-1β), pro-inflammatory eicosanoid expression (Prostaglandin E2, PGE2) and release of reactive oxygen species (ROS, superoxide and H2O2) following incubation of the cells with the surfaces. The morphology and cell viability of THP-1 cells were not affected by DEX-Ag whereas DEX-Ag minimized spreading of PMA-stimulated THP-1 cells and caused a reduction in cell viability (16% relative to other surfaces). Although DEX-Ag slightly enhanced release of ROS, the expression of pro-inflammatory cytokines remained minimal with similar levels of PGE2, as compared to the other surfaces studied. These results highlight low toxicity of DEX-Ag and hold promise for future applications in vivo.
在之前的工作中,我们开发了基于含有分散的 Ag NPs(~5nm,DEX-Ag)的葡聚糖的新型抗菌混合涂层,旨在为与植入手术相关的两种最常见的并发症(感染和植入物排斥)提供双重保护。然而,它们的血液-材料相互作用是未知的。在这项研究中,我们使用新鲜血液和两种免疫系统的细胞系(单核细胞(THP-1 细胞)和巨噬细胞(PMA 刺激的 THP-1 细胞)来评估 DEX-Ag 的血液相容性和生物相容性。玻璃、聚氨酯(PU)和裸葡聚糖(DEX)用作参考表面。PU、DEX 和 DEX-Ag 表现出非溶血特性。与玻璃(100%)相比,血小板在 PU、DEX 和 DEX-Ag 上的附着率分别为 15%、10%和 34%。此外,我们评估了细胞形态和活力、促炎细胞因子表达(TNF-α和 IL-1β)、促炎类花生酸表达(前列腺素 E2,PGE2)和细胞与表面孵育后活性氧(超氧化物和 H2O2)的释放。DEX-Ag 对 THP-1 细胞的形态和细胞活力没有影响,而 DEX-Ag 最小化了 PMA 刺激的 THP-1 细胞的扩散,并导致细胞活力降低(相对于其他表面为 16%)。尽管 DEX-Ag 略微增强了 ROS 的释放,但与研究的其他表面相比,促炎细胞因子的表达仍然很低,PGE2 的水平相似。这些结果突出了 DEX-Ag 的低毒性,并为其在体内的未来应用提供了希望。