Douglass Megan E, Goudie Marcus J, Pant Jitendra, Singha Priyadarshini, Hopkins Sean, Devine Ryan, Schmiedt Chad W, Handa Hitesh
School of Chemical, Materials and Biomedical Engineering, College of Engineering, University of Georgia, Athens, GA, USA.
Department of Small Animal Medicine and Surgery, University of Georgia, Athens, GA, USA.
ACS Appl Bio Mater. 2019 Jun 17;2(6):2539-2548. doi: 10.1021/acsabm.9b00237. Epub 2019 May 7.
Devices used for extracorporeal circulation are met with two major medical concerns: thrombosis and infection. A device that allows for anticoagulant-free circulation while reducing risk of infection has yet to be developed. We report the use of a copper nanoparticle (Cu NP) catalyst for the release of nitric oxide (NO) from the endogenous donor S-nitrosoglutathione (GSNO) in a coating applied to commercial Tygon S3 E-3603 poly(vinyl chloride) tubing in order to reduce adhered bacterial viability and the occurrence thrombosis for the first time in an animal model. Cu GSNO coated material demonstrated a nitric oxide (NO) release flux ranging from an initial flux of 6.3 ± 0.9 ×10 mol cm min to 7.1 ± 0.4 ×10 mol cm min after 4 h of release, while GSNO loops without Cu NPs only ranged from an initial flux of 1.1 ± 0.2 ×10 mol cm min to 2.3 ± 0.2 ×10 mol cm min after 4 h of release, indicating that the addition of Cu NPs can increase NO flux up to five times in the same 4 h period. Additionally, a 3-log reduction in and 1-log reduction in was observed in viable bacterial adhesion over a 24 h period compared to control loops. A Cell Counting Kit-8 (CCK-8) assay was used to validate no overall cytotoxicity towards 3T3 mouse fibroblasts. Finally, extracorporeal circuits were coated and exposed to 4 h of blood flow under an rabbit model. The Cu GSNO combination was successful in maintaining 89.3% of baseline platelet counts, while the control loops were able to maintain 67.6% of the baseline. These results suggest that the combination of Cu NPs with GSNO increases hemocompatibility and antimicrobial properties of ECC loops without any cytotoxic effects towards mammalian cells.
血栓形成和感染。一种能够在减少感染风险的同时实现无抗凝剂循环的设备尚未研发出来。我们报告了在商业泰贡S3 E - 3603聚氯乙烯管材涂层中使用铜纳米颗粒（Cu NP）催化剂从内源性供体S - 亚硝基谷胱甘肽（GSNO）释放一氧化氮（NO），以便在动物模型中首次降低附着细菌的活力并减少血栓形成的发生。Cu GSNO涂层材料显示出一氧化氮（NO）释放通量，从初始通量6.3±0.9×10⁻⁶ mol cm⁻² min⁻¹到释放4小时后为7.1±0.4×10⁻⁶ mol cm⁻² min⁻¹，而没有Cu NPs的GSNO环在释放4小时后仅从初始通量1.1±0.2×10⁻⁶ mol cm⁻² min⁻¹到2.3±0.2×10⁻⁶ mol cm⁻² min⁻¹，这表明在相同的4小时内添加Cu NPs可使NO通量增加多达五倍。此外，与对照环相比，在24小时内观察到存活细菌粘附减少3个对数级以及减少1个对数级。使用细胞计数试剂盒 - 8（CCK - 8）测定法验证对3T3小鼠成纤维细胞无总体细胞毒性。最后，在兔模型下对体外循环回路进行涂层并使其暴露于4小时的血流中。Cu GSNO组合成功地维持了基线血小板计数的89.3％，而对照环能够维持基线的67.6％。这些结果表明，Cu NPs与GSNO的组合增加了体外循环回路的血液相容性和抗菌性能，而对哺乳动物细胞没有任何细胞毒性作用。
