Department of Prosthetic Dentistry and Biomedical Materials Science, Hannover Medical School , Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Institute of Quantum Optics, Leibniz University of Hannover , Welfengarten 1, 30167 Hannover, Germany.
ACS Appl Mater Interfaces. 2017 Mar 22;9(11):9359-9368. doi: 10.1021/acsami.6b16159. Epub 2017 Mar 9.
Medical implants are commonly used in modern medicine but still harbor the risk of microbial infections caused by bacterial biofilms. As their retrospective treatment is difficult, there is a need for biomedical materials that inhibit bacterial colonization from the start without using antibacterial agents, as these can promote resistance development. The promising concept of slippery liquid-infused porous surfaces (SLIPS) possesses enormous potential for this purpose. In the present study, this principle was applied to titanium, a common material in implantology, and its biofilm-repellent properties were demonstrated. To simplify prospective approval of the medical device and to avoid chemical contamination, surface structuring was performed by ultrashort pulsed laser ablation. Four different structures (hierarchical micro- and nanosized spikes, microsized grooves, nanosized ripples, and unstructured surfaces) and five infusing perfluoropolyethers of different viscosities were screened; the best results were obtained with the biomimetic, hierarchical spike structure combined with lubricants of medium viscosities (20-60 cSt at 37 °C, 143 AZ, and GPL 104). The surfaces exhibited extremely low contact angle hysteresis, as is typical for liquid-infused materials and a reliable 100-fold reduction of human oral pathogen Streptococcus oralis biofilms. This characteristic was maintained after exposure to shear forces and gravity. The titanium SLIPS also inhibited adherence of human fibroblasts and osteoblasts. Toxicity tests supported the explanation that solely the surface's repellent properties are responsible for the vigorous prevention of the adhesion of bacteria and cells. This use of physically structured and liquid-infused titanium to avoid bioadhesion should support the prevention of bacterial implant-associated infections without the use of antibacterial agents.
医用植入物在现代医学中被广泛应用，但仍存在由细菌生物膜引起的微生物感染风险。由于其回顾性治疗较为困难，因此需要使用生物医学材料来预防细菌定植，这些材料在初始阶段就具有抑制细菌定植的作用，而无需使用抗菌剂，因为抗菌剂会促进耐药性的产生。具有前景的滑液浸润多孔表面（SLIPS）概念为此提供了巨大的潜力。在本研究中，该原理被应用于钛，一种植入物中常用的材料，并证明了其抗生物膜的特性。为了简化医疗器械的前瞻性批准并避免化学污染，通过超短脉冲激光烧蚀对表面进行结构化处理。筛选了四种不同的结构（分级微纳尺寸的刺、微尺寸的槽、纳米波纹和无结构表面）和五种不同粘度的全氟聚醚注入物；结果表明，具有仿生分级刺结构的表面与中粘度（37°C 时 20-60 cSt、143AZ 和 GPL 104）的润滑剂结合时，效果最佳。这些表面表现出极低的接触角滞后，这是液体浸润材料的典型特征，并且可以可靠地将人类口腔病原体变形链球菌生物膜减少 100 倍。这种特性在暴露于剪切力和重力后仍能保持。钛 SLIPS 还抑制了人成纤维细胞和骨细胞的黏附。毒性测试支持了这样的解释，即仅表面的排斥特性是防止细菌和细胞黏附的主要原因。这种使用物理结构化和液体浸润的钛来避免生物黏附，应该可以在不使用抗菌剂的情况下，预防与植入物相关的细菌感染。
