A state-of-the-art review of the fabrication and characteristics of titanium and its alloys for biomedical applications

Abstract

Abstract: Commercially pure titanium and titanium alloys have been among the most commonly used materials for biomedical applications since the 1950s. Due to the excellent mechanical tribological properties, corrosion resistance, biocompatibility, and antibacterial properties of titanium, it is getting much attention as a biomaterial for implants. Furthermore, titanium promotes osseointegration without any additional adhesives by physically bonding with the living bone at the implant site. These properties are crucial for producing high-strength metallic alloys for biomedical applications. Titanium alloys are manufactured into the three types of α, β, and α + β. The scientific and clinical understanding of titanium and its potential applications, especially in the biomedical field, are still in the early stages. This review aims to establish a credible platform for the current and future roles of titanium in biomedicine. We first explore the developmental history of titanium. Then, we review the recent advancement of the utility of titanium in diverse biomedical areas, its functional properties, mechanisms of biocompatibility, host tissue responses, and various relevant antimicrobial strategies. Future research will be directed toward advanced manufacturing technologies, such as powder-based additive manufacturing, electron beam melting and laser melting deposition, as well as analyzing the effects of alloying elements on the biocompatibility, corrosion resistance, and mechanical properties of titanium. Moreover, the role of titania nanotubes in regenerative medicine and nanomedicine applications, such as localized drug delivery system, immunomodulatory agents, antibacterial agents, and hemocompatibility, is investigated, and the paper concludes with the future outlook of titanium alloys as biomaterials.

Keywords: Advanced manufacturing; Antibacterial activity; Biocompatibility; Biomedical application; Functional properties; Titanium and titanium alloys.

Fig. 1

Titanium alloys used in medical devices throughout the entire human body

Fig. 2

a-e Brief illustration of the design and fabrication process of a patient-specific mandibular prosthetic implant for defects related to maxillofacial clinical applications

Fig. 3

a-d Various titanium alloys used in dental implants and their associated mechanical properties

Fig. 4

Schematic of anodization process to fabricate titanium dioxide nanotube (TNT) arrays: a oxide layer formation, b pit creation, c pit growth, d oxidation and field-assisted dissolution of the metallic region between the pores, e fully developed nanotubular configurations with f a corresponding top view and g cross-sectional view with inner and outer oxides

Fig. 5

a–c Schematic of a mixed system of anodization and PVD to deposit silver oxide on the edges of highly ordered TiO₂ nanotubular arrays on Ti64

Fig. 6

Strategies for controlling drug release from TNTs. a Controlling the diameter and length of nanotubes; b surface chemistry (hydrophobic, hydrophilic, charged); c tuning the nanotube opening by plasma polymerization; d degradation of dip-coated polymer film closing the nanotubes (PLGA or chitosan); e using drug nanocarriers (micelles) for multidrug delivery; f delayed/sequential drug release of drugs/drug carriers. External field-triggered drug release using g temperature, h magnetic field, i ultrasound, j light, and k radiofrequency with gold nanoparticles. Only a single nanotube structure is shown to present an array of TNTs

Fig. 7

Proposed mechanism of thermal-triggered drug release from polymer-coated TiO₂ nanotubular structures before a and after b heating. At low temperatures, the polymer capping forms a uniform protective layer on the nanotubes, resulting in a negligible level of uncontrolled drug release. However, heating of the implant to a specific temperature leads to the coil-to-globule transition of the polymer shell and the provision of preferred routes for drug diffusion