Micro- and nano-patterning of titanium surfaces for optimal osseointegration of orthopaedic implants

目前，由于需要支撑身体的重量和功能，矫形外科医生在承重关节置换（例如膝关节和髋关节）中使用的材料类型受到限制。常用的是钛（Ti）及其合金。然而，由于软组织形成加剧了骨与金属的直接接触，这种手术的使用寿命有限；这允许微动和最终失败。外科医生面临着越来越大的压力，首先是人口老龄化（在1950年，在发达国家，每一个65岁以上的人有9.3个20岁以下的人，到2025年，这一比例预计将达到每一个65岁以上的人有0.59个20岁以下的人）和相关的类风湿性关节炎问题，其次是更活跃的年轻人群和与骨关节炎相关的问题。由于目前这些手术的使用寿命（在挪威4762例手术的研究中，髋关节翻修手术的10年失败率为26%），在外科医生考虑手术之前，患者将不得不等待更长时间的疼痛。由于其材料特性，金属很难处理，因此迄今为止，表面处理促进直接骨生长并因此开发终身植入物的成功有限。我们最近已经证明，材料表面形貌的特定纳米尺度线索可能意味着干细胞分化为骨骼和干细胞分化为纤维组织之间的差异。此外，我们相信这仅仅是通过纳米级设计获得的一系列效果的一个介绍。材料表面如此微小的改变可以对干细胞产生如此大的影响，这清楚地表明纳米级设计可以对骨科生物材料的合理设计产生重大影响。发展“智能”骨科生物材料（如生物活性承重杆）的关键问题是：(1)能够形成合适的材料（例如钛），这是以前除了使用非特异性和随机粗化之外无法实现的；(2)实现机械交叉（微特征）和直接骨结合（纳米线和微线索）；(3)使用该技术生成原型设计，这将允许工业规模扩大和发展，从而显著影响和造福患者健康。

Currently, orthopaedic surgeons are limited to the type of materials they can use in load bearing joint replacements (e.g. knee and hip) due to the need to support the weight and function of the body. Commonly used are titanium (Ti) and its alloys. Such procedures, however, have a limited lifespan due to a combination of lack of direct bone contact with the metal exacerbated by soft tissue formation; this allows micromotion and ultimately failure. Surgeons face a mounting pressure due to firstly an aging population (in the developed world in 1950, there were 9.3 people under 20 for every person over 65, by 2025 this ratio is forecast to be 0.59 people under 20 for every person older than 65) and associated problems of rheumatoid arthritis and secondly a more sports active younger populations and problems associated with osteoarthritis. Due to the present lifespan of these procedures (The 10 year failure rate for revision hip surgery was 26% in a Norwegian study of 4762 operations) patients will have to wait longer with pain before surgeons will consider operations. The metals are hard to work with due their material properties and so success to date with surface treatments to encourage direct bone growth and hence develop implants for life have been limited.We have recently demonstrated that specific nanoscale cues in the topography of a material surface can mean the difference between stem cell differentiation to bone and stem cell differentiation to fibrous tissue. Furthermore, we believe that this is merely an introduction to the range of effects obtainable through nanoscale design. That such small alterations in the material surface can have such large effects on stem cells makes it clear that nanoscale design could have significant impact in the rational design of orthopaedic biomaterials. Crucial issues for the development of 'intelligent' orthopaedic biomaterials such as bioactive load-bearing stems are: (1) ability to pattern into suitable materials (e.g. Ti) this has not previously been achieved other than using non-specific and random roughening, (2) achieving both mechanical interdigitation (microfeatures) and direct bone bonding (nanocues and microcues) and (3) generating prototype designs using this technology, which will permit the scale-up and development by industry thereby significantly impacting and benefiting patient health.