Centre for Antimicrobial Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore.
Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
ACS Appl Mater Interfaces. 2021 Jul 28;13(29):33745-33755. doi: 10.1021/acsami.1c00340. Epub 2021 Jul 19.
Bacterial colonization on biomedical devices often leads to biofilms that are recalcitrant to antibiotic treatment and the leading cause of hospital-acquired infections. We have invented a novel pretreatment chemistry for device surfaces to produce a high-density three-dimensional (3-D) network of covalently linked S-nitrosothiol (RSNO), which is a nitric oxide (NO) donor. Poly(polyethylene glycol-hydroxyl-terminated) (i.e., PPEG-OH) brushes were grafted from an ozone-pretreated polyurethane (PU) surface. The high-density hydroxyl groups on the dangling PPEG-OH brushes then underwent condensation with a mercapto-silane (i.e., MPS, mercaptopropyl trimethoxysilane) followed by S-nitrosylation to produce a 3-D network of NO-releasing RSNO to form the PU/PPEG-OH-MPS-NO coating. This 3-D coating produces NO flux of up to 7 nmol/(cm min), which is nearly 3 orders of magnitude higher than the picomole/(cm min) levels of other NO-releasing biomedical implants previously reported. The covalent immobilization of RSNO avoids donor leaching and reduces the risks of cytotoxicity arising from leachable RSNO. Our coated PU surfaces display good biocompatibility and exhibit excellent antibiofilm formation activity (up to 99.99%) against a broad spectrum of Gram-positive and Gram-negative bacteria. Further, the high-density RSNO achieves nearly 99% and 99.9% reduction of () and methicillin-resistant (MRSA) in a murine subcutaneous implantation infection model. Our surface chemistry to create high NO payload without NO-donor leaching can be applied to many biomedical devices.
生物医学设备上的细菌定植通常会导致生物膜的形成，而生物膜对抗生素治疗具有抗性，是医院获得性感染的主要原因。我们发明了一种用于设备表面的新型预处理化学物质，可产生高密度的三维（3-D）共价连接的 S-亚硝硫醇（RSNO）网络，这是一种一氧化氮（NO）供体。聚（聚乙二醇-羟基封端）（即 PPEG-OH）刷从臭氧预处理的聚氨酯（PU）表面接枝。悬空的 PPEG-OH 刷上的高密度羟基随后与巯基-硅烷（即 MPS，巯丙基三甲氧基硅烷）发生缩合，然后进行 S-亚硝化，生成释放 NO 的 RSNO 的 3-D 网络，形成 PU/PPEG-OH-MPS-NO 涂层。这种 3-D 涂层产生的 NO 通量高达 7 nmol/（cm min），比以前报道的其他释放 NO 的生物医学植入物的皮摩尔/（cm min）水平高出近 3 个数量级。RSNO 的共价固定避免了供体浸出，并降低了可浸出 RSNO 引起细胞毒性的风险。我们涂覆的 PU 表面显示出良好的生物相容性，并对广谱革兰氏阳性和革兰氏阴性细菌表现出出色的抗生物膜形成活性（高达 99.99%）。此外，高密度 RSNO 在小鼠皮下植入感染模型中实现了对（）和耐甲氧西林金黄色葡萄球菌（MRSA）的近 99%和 99.9%的减少。我们创造高 NO 有效负载而不发生 NO 供体浸出的表面化学可以应用于许多生物医学设备。
