Recent Advances in Copper-Doped Titanium Implants

Abstract

Titanium (Ti) and its alloys have been extensively used as implant materials in clinical practice due to their high corrosion resistance, light weight and excellent biocompatibility. However, the insufficient intrinsic osteogenic capacity of Ti and its alloys impedes bone repair and regeneration, and implant-related infection or inflammation remains the leading cause of implant failure. Bacterial infections or inflammatory diseases constitute severe threats to human health. The physicochemical properties of the material are critical to the success of clinical procedures, and the doping of Cu into Ti implants has been confirmed to be capable of enhancing the bone repair/regeneration, angiogenesis and antibacterial capability. This review outlines the recent advances in the design and preparation of Cu-doped Ti and Ti alloy implants, with a special focus on various methods, including plasma immersion implantation, magnetron sputtering, galvanic deposition, microarc oxidation and sol-gel synthesis. More importantly, the antibacterial and mechanical properties as well as the corrosion resistance and biocompatibility of Cu-doped Ti implants from different methods are systematically reviewed, and their prospects and limitations are also discussed.

Keywords: biocompatibility; copper doping; implant; implant–bacteria interactions; synthetic methods; titanium and titanium alloys.

Figure 1

Schematic diagram of the biofilm formation process. The dashed area represents the initial stages of biofilm formation. Reproduced with permission from Ref. [30]. Copyright 2020, Multidisciplinary Digital Publishing Institute.

Figure 2

Schematic and structural diagrams of ion implantation. Reproduced with permission from Ref. [46]. Copyright 2019, American Vacuum Society.

Figure 3

(a) Hardness average values (40–60 nm) detected by nanoindentation tests for various samples. (b) Polarization curves of various samples. (c) Proliferative activity of HUVECs cultured on various surfaces. Antibacterial rates of various samples against S. aureus (d) and E. coli (e). Reproduced with permission from Ref. [51]. Copyright 2020, KeAi Publishing LTD. (f) Hardness average values (40–60 nm) detected by nanoindentation tests for various samples. (g) Proliferative activity of HUVECs cultured on various surfaces. Antibacterial rates of various samples against S. aureus (h) and E. coli (i). *: p < 0.05, **: p < 0.01, ***: p < 0.001. Reproduced with permission from Ref. [53]. Copyright 2018, American Chemical Society.

Figure 4

(a) Morphology of MG63 cells on the surfaces of Ti and Ti-Cu alloys. (b) Viabilities of MG63 cells determined by measurement of the optical density. Osteogenesis-related factors analysis. (c) ALP activity of cells on Ti and Ti-Cu alloy. * Ti-Cu alloy facilitated the early differentiation of MG63 cells. Quantitative colorimetric results of (d) ECM mineralization nodules and (e) collagen secretion. Reproduced with permission from Ref. [67]. Copyright 2019, Springer.

Figure 5

Schematic representation for anti-infective mechanism of TiCu implants in the ligature and sucrose-rich diet-induced model. Reproduced with permission from Ref. [38]. Copyright 2021, KeAi Publishing LTD.

Figure 6

Schematic diagram of the MAO experimental device. Reproduced with permission from Ref. [34]. Copyright 2018, Elsevier.

Figure 7

Response of endothelial cells: (a) fluorescence images and (b) quantitative results of cell adhesion; (c) fluorescence images of endothelial cells cultured on the MAO coatings with F-actins stained with FITC (green) and nuclei stained with DAPI (blue); (d) fluorescence images of live/dead staining of endothelial cells on the MAO coatings; (e) MTT results of endothelial cells on the MAO coatings; and (f) VEGF concentrations secreted by endothelial cells. **: p < 0.01 compared to P-Ti, ##: p < 0.01 compared to 0 Cu, &&: p < 0.01 compared to 3.0 Cu, *: p < 0.05 compared to P-Ti. Reproduced with permission from Ref. [34]. Copyright 2018, Elsevier.

Figure 8

The influence of material composition on the biological properties of nanocrystalline thin films based on Cu and Ti. Reproduced with permission from Ref. [114]. Copyright 2020, Multidisciplinary Digital Publishing Institute.