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

全髋关节和膝关节置换术（THR & TKR）的需求在全球范围内稳步增长。这是由于人口老龄化、肥胖人数增加以及人们转向更积极的生活方式；总之，这些因素导致更多的骨关节炎和关节软骨和软骨下骨退化。这类骨科种植体失败的两个主要原因是松动（由于骨与种植体接触不良）和感染（由于细菌浸润和生物膜形成）。在THR/TKR的病例中，据报道，原发性手术中关节感染的发生率为1%- 4%，翻修手术中高达30%。我们之前的研究表明，钛（许多骨科植入物都是由钛制成的）表面上的某些纳米结构表面可以同时具有杀菌和生物活性（骨形成）。然而，到目前为止，大多数工作都是在纳米结构的二维表面上进行的，而不是真正的植入物表面。该项目旨在进行基于纳米结构表面的3D多孔钛植入物的体外和临床前研究，从而将我们目前对2D的理解转化为真正的3D植入物。我们已经组建了一支来自布里斯托尔大学、格拉斯哥大学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项目的研究成果集中在二维表面上杀菌地形的基础科学上，并将其应用于现实世界。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，以清晰的愿景将新的智能细胞指导表面应用于骨科植入物。我们希望通过避免因种植体松动和感染而需要翻修，提高需要种植体的患者的生活质量，节省NHS的费用。

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.