Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, New York, 13699, USA.
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, 16802, USA.
J Biomed Mater Res B Appl Biomater. 2023 Aug;111(8):1533-1545. doi: 10.1002/jbm.b.35252. Epub 2023 Mar 25.
Biomaterial-associated microbial infection is one of the most frequent and severe complications associated with the use of biomaterials in medical devices. In previous studies, we developed new fluorinated polyphosphazenes, poly[bis(octafluoropentoxy) phosphazene] (OFP) and crosslinkable OFP (X-OFP), and demonstrated the inhibition of bacterial adhesion and biofilm formation, thereby controlling microbial infection. In this study, two additional fluorinated polyphosphazenes (PPs, defined as LS02 and LS03) with fluorophenoxy-substituted side groups, 4-fluorophenoxy and 4-(trifluoromethyl)phenoxy, respectively, based on X-OFP general structure, were synthesized and applied as coatings on stainless steel. The linkage of fluorophenoxy groups to the P-N backbone of PPs was found to increase the surface stiffness and significantly reduced Staphylococcus bacterial adhesion and inhibited biofilm formation. It also significantly reduced microbial infection compared to OFP, our prior X-OFPs or poly[bis(trifluoroethoxy) phosphazene] (TFE). The biofilm experiments show that the newly synthesized PPs LS02 and LS03 are biofilm free up to 28 days. Plasma coagulation and platelet adhesion/activation experiments also demonstrated that new PPs containing fluorophenoxy side groups are hemocompatible. The development of new crosslinkable fluorinated PPs containing fluorophenoxy-substituted side groups provides a new generation of polyphosphazene materials for medical devices with improved resistance to microbial infections and thrombosis formation.
生物材料相关性微生物感染是医疗器械中使用生物材料最常见和最严重的并发症之一。在之前的研究中,我们开发了新型氟化聚膦腈,聚[双(辛氟戊氧基)膦腈](OFP)和可交联的 OFP(X-OFP),并证明了其可以抑制细菌黏附和生物膜形成,从而控制微生物感染。在这项研究中,基于 X-OFP 的通用结构,我们又合成了两种具有氟苯氧基取代侧基的另外两种氟化聚膦腈(PP,分别定义为 LS02 和 LS03),即 4-氟苯氧基和 4-(三氟甲基)苯氧基。将氟苯氧基基团连接到 PPs 的 P-N 主链上,发现其增加了表面硬度,并显著减少了金黄色葡萄球菌的黏附,并抑制了生物膜的形成。与 OFP、我们之前的 X-OFPs 或聚[双(三氟乙氧基)膦腈](TFE)相比,它还显著降低了微生物感染的风险。生物膜实验表明,新合成的 PPs LS02 和 LS03 可以在 28 天内保持无生物膜状态。血浆凝固和血小板黏附和激活实验也表明,含有氟苯氧基侧基的新型 PPs 具有良好的血液相容性。新型可交联含氟苯氧基取代侧基的氟化 PPs 的开发为具有改善的抗微生物感染和血栓形成能力的医疗器械提供了新一代聚膦腈材料。