In vitro and in vivo studies of 3D orthopaedic implants with cell-instructive nanotopographies

全球对全髋关节和膝关节置换术(THR和TKR)的需求一直在稳步增长。这是由于人口老龄化、肥胖症的增加以及向更活跃的生活方式的转变；这些因素共同导致了更多的骨关节炎以及关节中软骨和软骨下骨的退化。这类骨科植入物失败的两个主要原因是松动(由于与植入物接触不良)和感染(由于细菌渗透和生物膜形成)。在THR/TKR的病例中，据报道，初次手术关节感染的发生率为1%-4%，而翻修手术的关节感染发生率高达30%。我们之前的工作表明，钛表面的某些纳米结构表面(许多骨科植入物都是由钛制成的)既可以杀菌，也可以具有生物活性(成骨)。然而，到目前为止，大多数工作都是在纳米结构的2D表面上进行的，而不是真正的种植体表面。本项目的目的是基于纳米结构表面的3D多孔钛种植体进行体外和临床前研究，从而将我们目前对2D的理解转化为真实的3D种植体。我们已经组建了一个来自布里斯托尔、格拉斯哥和剑桥大学的多学科团队，与临床和工业合作伙伴合作，将我们以前EPSRC项目的研究成果推进到现实世界的应用中，这些项目专注于2D表面上杀菌地形的基础科学。我们将汇集生物材料、纳米技术、干细胞生物学、微生物学和临床前研究方面的专业知识，以明确的愿景将新型智能细胞教育表面应用于整形外科植入物。我们希望通过避免因种植体松动和感染而需要修改的情况，来提高需要植入的患者的生活质量，并节省NHS的成本。

The demand for total hip and knee replacements (THR & TKR) has been steadily increasing worldwide. This is due to an ageing population, the rise in obesity and a change to more active lifestyles; together, these factors are leading to more osteoarthritis and degeneration of cartilage and subchondral bone in joints. The two leading causes of this type of orthopaedic implant failure are loosening (due to poor bone contact with the implant) and infection (due to bacterial infiltration and biofilm formation). In the case of THR/TKR, the incidence rate of joint infections is reported to be 1%- 4% in primary surgery and up to 30% in revision surgery. Our previous work showed that certain nanostructured surfaces on titanium (many orthopaedic implants are made from titanium) surfaces could be both bactericidal and bioactive (bone forming). However, most of the work so far was carried out on nanostructured 2D surfaces rather than real implant surfaces.This project is aimed at conducting in vitro and pre-clinical studies based on 3D porous Ti implants with nanostructured surfaces, hence translating our current understanding in 2D into real 3D implants. We have assembled a multidisciplinary team from universities of Bristol, Glasgow and Cambridge, in partnership with clinical and industrial partners, to progress our research findings from previous EPSRC projects focusing on the basic science of bactericidal topographies on 2D surfaces towards the real world applications. We will bring together expertise in biomaterials, nanotechnology, stem cell biology, microbiology and pre-clinical studies, with a clear vision to apply new smart cell-instructive surfaces to orthopaedic implants. We hope to improve the quality of life of patients who require implants and save the costs of NHS by avoiding the need for revision due to implant loosening and infection.