School of Chemical, Materials and Biomedical Engineering, College of Engineering, University of Georgia, Athens, Georgia, USA.
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, USA.
J Biomed Mater Res A. 2023 Apr;111(4):451-464. doi: 10.1002/jbm.a.37493. Epub 2023 Jan 3.
Graphene oxide (GO) nanosheets are a promising class of carbon-based materials suitable for application in the construction of medical devices. These materials have inherent antimicrobial properties based on sheet size, but these effects must be carefully traded off to maintain biocompatibility. Chemical modification of functional groups to the lattice structure of GO nanosheets enables unique opportunities to introduce new surface properties to bolster biological effects. Herein, we have developed nitric oxide (NO)-releasing GO nanosheets via immobilization of S-nitrosothiol (RSNO) moieties to GO nanosheets (GO-[NH] -SNO). These novel RSNO-based GO nanosheets were characterized for chemical functionality via Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, and colorimetric assays for functional group quantification. Stoichiometric control of the available RSNO groups functionalized onto the nanosheets was studied using chemiluminescence-based NO detection methods, showing highly tunable NO release kinetics. Studies of electrical stimulation and subsequent electrochemical reduction of the nanosheets demonstrated further tunability of the NO release based on stimuli. Finally, nanosheets were evaluated for cytotoxicity and antibacterial effects, showing strong cytocompatibility with human fibroblasts in parallel to broad antibacterial and anti-biofilm effects against both Gram-positive and Gram-negative strains. In summary, derivatized GO-(NH) -SNO nanosheets were shown to have tunable NO release properties, enabling application-specific tailoring for diverse biomedical applications such as antimicrobial coatings and composite fillers for stents, sensors, and other medical devices.
氧化石墨烯（GO）纳米片是一类很有前途的碳基材料，适用于医疗器械的构建。这些材料具有基于片层大小的固有抗菌性能，但为了保持生物相容性，这些效果必须仔细权衡。通过将功能基团化学修饰到 GO 纳米片的晶格结构上，可以为引入新的表面特性以增强生物学效应提供独特的机会。在此，我们通过将 S-亚硝基硫醇（RSNO）部分固定到 GO 纳米片上（GO-[NH]-SNO），开发了释放一氧化氮（NO）的 GO 纳米片。通过傅里叶变换红外光谱、X 射线光电子能谱和比色法测定功能团定量对这些新型基于 RSNO 的 GO 纳米片进行了化学功能的表征。使用基于化学发光的 NO 检测方法研究了纳米片上功能化的可用 RSNO 基团的化学计量控制，显示出高度可调的 NO 释放动力学。对纳米片的电刺激和随后的电化学还原的研究表明，基于刺激物进一步可调谐 NO 的释放。最后，评估了纳米片的细胞毒性和抗菌效果，结果表明，它们与人成纤维细胞具有很强的细胞相容性，同时对革兰氏阳性和革兰氏阴性菌株具有广谱的抗菌和抗生物膜作用。总之，衍生化的 GO-(NH)-SNO 纳米片具有可调的 NO 释放特性，能够针对各种生物医学应用（如抗菌涂层和支架、传感器和其他医疗器械的复合材料填充剂）进行特定应用的定制。
