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

在德国，医院获得性感染（医院感染）是一个主要的社会经济问题，每年有多达60万例病例和4万例死亡。植入物占所有医院感染的45%。这些生物材料相关感染（BAIs）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%的创伤学和骨科植入物发生BAIs。在开放性骨折患者中，以金属生物材料为主要材料的骨融合术与高达40%的感染相关。钛种植体最常用于骨合成领域。近年来，由于耐抗生素菌株的增加，感染控制的可能性变得复杂。老年患者由于整体健康状况较弱，更容易受到感染，随着医疗器械植入数量的同时增加，显然需要新的和不同的方法来对抗BAIs。目前使用的大多数植入物没有防御微生物定植的机制，因此，往往是局部或全身感染的起点。目前讨论的解决方案，如金属（如银或铜）或含有抗生素的种植体涂层具有缺点（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），并且除了少数例外，在临床条件下产生了令人不满意的结果。一种减少微生物粘附在生物材料表面的新方法是使用纳米粗糙或纳米结构的生物材料，例如在钛植入物上进行骨接触。我们小组的初步研究结果令人鼓舞：在粗糙度为2至6 nm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性具有统计学意义上的显著降低。然而，纳米粗糙度如何干扰病原微生物尚不清楚，纳米粗糙表面的粘附机制也是一个谜。因此，我们的目的是揭示钛的纳米粗糙度和微生物粘附之间的因果关系。目前，材料科学家和微生物学家之间缺乏合作是纳米粗糙抗菌生物材料领域获得知识和科学进步的主要障碍。本项目将有助于缩小对纳米粗糙表面微生物粘附机制的理解差距，并促进两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.