Antimicrobial Effect of Nano-Rough Titanium Surfaces: Reduction of Microbial Adhesion and Mechanisms of Reduction

在德国，每年有多达60万例病例和4万人死亡，医院感染(医院感染)是一个主要的社会经济问题。植入物占所有医院感染的45%。这些生物材料相关感染(BaI)最常与留置医疗器械材料表面的微生物定植有关。大约2-6%的创伤和骨科植入物会发生Bais。骨接骨术主要是用金属生物材料对准和固定骨折，在开放性骨折患者中，与高达40%的感染有关。钛植入物最常用于骨接合领域。近年来，由于抗药性细菌株的增加，感染控制的可能性变得复杂。随着对老年患者的医疗器械植入数量的同时增加，这些老年患者由于其虚弱的总体健康状况而更容易受到感染，显然需要新的和不同的方法来抗击Bais。今天使用的大多数植入物没有针对微生物定植的防御机制，因此往往是局部或系统感染的起点。目前讨论的解决方案，如金属(如银或铜)或含抗生素的种植体涂层有缺点(细胞毒性、不利的活性物质释放动力学、作用时间有限、促进耐药性的发展等)。而且，除了少数例外，在临床条件下得出的结果并不令人满意。为了减少微生物在生物材料表面的黏附，从而潜在地减少BaI的数量，一种新的方法是使用纳米粗糙或纳米结构的生物材料，例如用于骨接触的钛植入物。我们团队的初步研究结果令人鼓舞：在粗糙度从2纳米到6纳米的钛表面上，我们观察到与光滑表面相比，粗糙表面上的微生物粘附率在统计上显著降低。然而，纳米粗糙度如何干扰病原微生物的研究尚不清楚，纳米粗糙度表面的黏附机制也是一个谜。因此，我们的目标是揭开钛纳米粗糙度和微生物粘附性之间的因果关系。在纳米粗糙抗菌生物材料领域获得知识和取得科学进展的一个主要障碍是目前材料科学家和微生物学家之间严重缺乏合作。该项目将有助于弥合在理解微生物在纳米粗糙表面上的附着机制方面的差距，并促进这两个学科之间的协同合作。

With up to 600,000 cases and 40,000 deaths per year in Germany, hospital-acquired infections (nosocomial infections) are a major socio-economic problem. Implants account for up to 45% of all nosocomial infections. These biomaterials associated infections (BAIs) are most frequently associated with microbial colonization on the materials surfaces of the indwelling medical devices. BAIs occur with approximately 2-6 % of traumatology and orthopedic implants. Osteosynthesis, the alignment and fixation of bone fractures with mostly metallic biomaterials, is associated with infection of up to 40% in patients with open bone fractures. Titanium implants are most often used in the field of osteosynthesis. The possibilities of infection control have been complicated in recent years due to an increase in antibiotic resistant strains of bacteria. With a simultaneous increase of the number of medical device implantations in elderly patients who are more susceptible to infections because of their frail general health state, the need for fresh and different approaches to fight BAIs is apparent. Most implants used today have no defense mechanisms against microbial colonization and, therefore, are often the starting point of local or systemic infections. The presently discussed solutions, such as metals (e.g. silver or copper) or antibiotic-containing implant coatings have disadvantages (cytotoxicity, unfavorable active substance release kinetics, limited duration of action, promoting the development of drug resistance, etc.) and, with few exceptions, yielded unsatisfactory results under clinical conditions. A fresh approach to reduce microbial adhesion on biomaterials surfaces and, thus, potentially reduce the number of BAIs is using nano-rough or nanostructured biomaterials, e.g. on titanium implants for bone contact. Preliminary research results of our groups are encouraging: on titanium surfaces with roughnesses from 2 to 6 nm, we observed a statistically significantly lower microbial adhesion on the rougher surfaces compared to the smoother surfaces. However, how nano-roughness interferes with pathogenic microbes is yet unclear and the mechanism of adhesion on nano-rough surfaces is an enigma. We, therefore, aim to unravel the causal relationship between nano-roughness of titanium and microbial adhesion. A major obstacle to gain knowledge and scientific progress in the field of nano-rough antimicrobial biomaterials is the current substantial lack of cooperation between materials scientists and microbiologists. This project will help to close the gaps in understanding the mechanisms of microbial adhesion on nano-rough surfaces as well as promote synergistic cooperation between the two disciplines.