Tabish Tanveer A, Hussain Mian Zahid, Zhu Yangzhi, Xu Jiabao, Huang Wei E, Diotallevi Marina, Narayan Roger J, Crabtree Mark J, Khademhosseini Ali, Winyard Paul G, Lygate Craig A
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, British Heart Foundation (BHF) Centre of Research Excellence, University of Oxford, Headington, Oxford OX3 7BN, United Kingdom.
School of Natural Sciences, Department of Chemistry, Chair of Inorganic and Metal-Organic Chemistry, Technical University of Munich (TUM), Lichtenbergstraße 4, 85748 Garching, Germany.
Appl Phys Rev. 2024 Sep 24;11(3). doi: 10.1063/5.0192379. eCollection 2024 Sep 1.
Drug-eluting stents are commonly utilized for the treatment of coronary artery disease, where they maintain vessel patency and prevent restenosis. However, problems with prolonged vascular healing, late thrombosis, and neoatherosclerosis persist; these could potentially be addressed via the local generation of nitric oxide (NO) from endogenous substrates. Herein, we develop amine-functionalized graphene as a NO-generating coating on polylactic acid (PLA)-based bioresorbable stent materials. A novel catalyst was synthesized consisting of polyethyleneimine and polyethylene glycol bonded to graphene oxide (PEI-PEG@GO), with physicochemical characterization using x-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. In the presence of 10 M S-nitrosoglutathione (GSNO) or S-nitroso-N-acetylpenicillamine (SNAP), PEI-PEG@GO catalyzed the generation of 62% and 91% of the available NO, respectively. Furthermore, PEI-PEG@GO enhanced and prolonged real-time NO generation from GSNO and SNAP under physiological conditions. The uniform coating of PEI-PEG@GO onto stent material is demonstrated via an optimized simple dip-coating method. The coated PLA maintains good biodegradability under accelerated degradation testing, while the PEI-PEG@GO coating remains largely intact. Finally, the stability of the coating was demonstrated at room temperature over 60 days. In conclusion, the innovative conjugation of polymeric amines with graphene can catalyze the generation of NO from -nitrosothiols at physiologically relevant concentrations. This approach paves the way for the development of controlled NO-generating coatings on bioresorbable stents in order to improve outcomes in coronary artery disease.
药物洗脱支架通常用于治疗冠状动脉疾病,可维持血管通畅并防止再狭窄。然而,血管愈合时间延长、晚期血栓形成和新生动脉粥样硬化等问题仍然存在;这些问题有可能通过内源性底物局部生成一氧化氮(NO)来解决。在此,我们开发了胺功能化石墨烯,作为基于聚乳酸(PLA)的生物可吸收支架材料上的NO生成涂层。合成了一种新型催化剂,由聚乙烯亚胺和聚乙二醇键合到氧化石墨烯上(PEI-PEG@GO),并使用X射线衍射、拉曼光谱、傅里叶变换红外光谱和热重分析进行了物理化学表征。在存在10 M S-亚硝基谷胱甘肽(GSNO)或S-亚硝基-N-乙酰青霉胺(SNAP)的情况下,PEI-PEG@GO分别催化生成了62%和91%的可用NO。此外,PEI-PEG@GO在生理条件下增强并延长了GSNO和SNAP的实时NO生成。通过优化的简单浸涂方法证明了PEI-PEG@GO在支架材料上的均匀涂层。在加速降解测试下,涂覆的PLA保持良好的生物降解性,而PEI-PEG@GO涂层基本保持完整。最后,在室温下60多天证明了涂层的稳定性。总之,聚合物胺与石墨烯的创新结合可以在生理相关浓度下催化从亚硝基硫醇生成NO。这种方法为在生物可吸收支架上开发可控的NO生成涂层铺平了道路,以改善冠状动脉疾病的治疗效果。