Reger Nina A, Meng Wilson S, Gawalt Ellen S
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282, USA.
Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
J Funct Biomater. 2017 Jun 21;8(2):20. doi: 10.3390/jfb8020020.
Titanium and titanium alloy materials are commonly used in joint replacements, due to the high strength of the materials. Pathogenic microorganisms can easily adhere to the surface of the metal implant, leading to an increased potential for implant failure. The surface of a titanium-aluminum-vanadium (Ti-6Al-4V) metal oxide implant material was functionalized to deliver an small antibacterial molecule, nitric oxide. -nitroso-penicillamine, a -nitrosothiol nitric oxide donor, was covalently immobilized on the metal oxide surface using self-assembled monolayers. Infrared spectroscopy was used to confirm the attachment of the -nitrosothiol donor to the Ti-Al-4V surface. Attachment of -nitroso-penicillamine resulted in a nitric oxide (NO) release of 89.6 ± 4.8 nmol/cm² under physiological conditions. This low concentration of nitric oxide reduced and growth by 41.5 ± 1.2% and 25.3 ± 0.6%, respectively. Combining the -nitrosothiol releasing Ti-6Al-4V with tetracycline, a commonly-prescribed antibiotic, increased the effectiveness of the antibiotic by 35.4 ± 1.3%, which allows for lower doses of antibiotics to be used. A synergistic effect of ampicillin with -nitroso-penicillamine-modified Ti-6Al-4V against was not observed. The functionalized Ti-6Al-4V surface was not cytotoxic to mouse fibroblasts.
由于材料强度高,钛及钛合金材料常用于关节置换。致病微生物很容易附着在金属植入物表面,导致植入物失效的可能性增加。对钛铝钒(Ti-6Al-4V)金属氧化物植入材料的表面进行功能化处理,以递送一种小抗菌分子——一氧化氮。使用自组装单分子层将一种亚硝基硫醇一氧化氮供体——亚硝基青霉胺共价固定在金属氧化物表面。利用红外光谱法确认亚硝基硫醇供体与Ti-Al-4V表面的附着情况。亚硝基青霉胺的附着导致在生理条件下一氧化氮(NO)释放量为89.6±4.8 nmol/cm²。这种低浓度的一氧化氮分别使金黄色葡萄球菌和大肠杆菌的生长减少了41.5±1.2%和25.3±0.6%。将释放亚硝基硫醇的Ti-6Al-4V与常用抗生素四环素联合使用,可使抗生素的效力提高35.4±1.3%,从而可以使用更低剂量的抗生素。未观察到氨苄青霉素与亚硝基青霉胺修饰的Ti-6Al-4V对金黄色葡萄球菌的协同作用。功能化的Ti-6Al-4V表面对小鼠成纤维细胞无细胞毒性。