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基于 S-亚硝基谷胱甘肽的一氧化氮释放纳米纤维在生物医学应用中表现出双重抗菌和抗血栓形成活性。

S-Nitrosoglutathione-Based Nitric Oxide-Releasing Nanofibers Exhibit Dual Antimicrobial and Antithrombotic Activity for Biomedical Applications.

机构信息

School of Chemical, Materials and Biomedical Engineering, College of Engineering, University of Georgia, Athens, GA, 30602, USA.

出版信息

Macromol Biosci. 2021 Jan;21(1):e2000248. doi: 10.1002/mabi.202000248. Epub 2020 Oct 5.

Abstract

The novel use of nanofibers as a physical barrier between blood and medical devices has allowed for modifiable, innovative surface coatings on devices ordinarily plagued by thrombosis, delayed healing, and chronic infection. In this study, the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) is blended with the biodegradable polymers polyhydroxybutyrate (PHB) and polylactic acid (PLA) for the fabrication of hemocompatible, antibacterial nanofibers tailored for blood-contacting applications. Stress/strain behavior of different concentrations of PHB and PLA is recorded to optimize the mechanical properties of the nanofibers. Nanofibers incorporated with different concentrations of GSNO (10, 15, 20 wt%) are evaluated based on their NO-releasing kinetics. PLA/PHB + 20 wt% GSNO nanofibers display the greatest NO release over 72 h (0.4-1.5 × 10  mol mg min ). NO-releasing fibers successfully reduce viable adhered bacterial counts by ≈80% after 24 h of exposure to Staphylococcus aureus. NO-releasing nanofibers exposed to porcine plasma reduce platelet adhesion by 64.6% compared to control nanofibers. The nanofibers are found noncytotoxic (>95% viability) toward NIH/3T3 mouse fibroblasts, and 4',6-diamidino-2-phenylindole and phalloidin staining shows that fibroblasts cultured on NO-releasing fibers have improved cellular adhesion and functionality. Therefore, these novel NO-releasing nanofibers provide a safe antimicrobial and hemocompatible coating for blood-contacting medical devices.

摘要

新型纳米纤维作为血液与医疗器械之间的物理屏障,可对通常易发生血栓、愈合延迟和慢性感染的医疗器械进行改良和创新的表面涂层处理。在这项研究中,将一氧化氮(NO)供体 S-亚硝基谷胱甘肽(GSNO)与可生物降解的聚合物聚羟基丁酸酯(PHB)和聚乳酸(PLA)混合,用于制造适用于与血液接触的应用的具有血液相容性和抗菌性的纳米纤维。记录不同浓度 PHB 和 PLA 的应力/应变行为,以优化纳米纤维的机械性能。基于其 NO 释放动力学,评估掺入不同浓度 GSNO(10、15、20wt%)的纳米纤维。PLA/PHB+20wt%GSNO 纳米纤维在 72 小时内释放出最大的 NO(0.4-1.5×10  mol mg min )。暴露于金黄色葡萄球菌 24 小时后,释放 NO 的纤维可成功将活菌粘附细菌计数减少约 80%。与对照纳米纤维相比,暴露于猪血浆的 NO 释放纳米纤维可将血小板粘附减少 64.6%。研究发现,这些纳米纤维对 NIH/3T3 小鼠成纤维细胞无细胞毒性(>95%活力),并且 4',6-二脒基-2-苯基吲哚和鬼笔环肽染色表明,在释放 NO 的纤维上培养的成纤维细胞具有改善的细胞粘附和功能。因此,这些新型的 NO 释放纳米纤维为与血液接触的医疗器械提供了一种安全的抗菌和血液相容性涂层。

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