Research and development of antibacterial titanium alloy materials and technologies
1 Introduction
Titanium (Ti) and its alloys have the characteristics of low density, high strength, and excellent corrosion resistance, and were originally used in the aviation industry. In the early 1940s, titanium and its alloys were first introduced into the medical field. After more than half a century of development, pure titanium and Ti6A14V alloy, as the most representative titanium-based medical metal materials, have been used in many medical clinics, especially in the fields of orthopedics and dentistry, replacing stainless steel and cobalt-based alloys in large quantities. However, titanium alloy is a type of biologically inert material that has no antibacterial properties and is powerless against infection problems caused by implants. At present, magnetron sputtering, electrochemical deposition, ion implantation, micro-arc oxidation and other methods are usually used to load inorganic or organic antibacterial agents on the surface of medical titanium alloys, thereby giving them antibacterial properties. The advantages of antibacterial coatings prepared through surface modification are obvious, but there are still shortcomings, such as the relatively complex coating process, increased production costs, poor bonding between the coating and the substrate, easy wear of the coating, and poor long-term antibacterial performance wait. In response to the infection problems caused by implanted titanium alloys and the lack of antibacterial coatings, people have begun to try to develop new antibacterial titanium alloys with their own antibacterial functions by adjusting the alloy composition.
2. Antibacterial mechanism of antibacterial titanium alloy
The spread of bacteria is closely related to the formation of bacterial biofilms. The formation process of bacterial biofilms is shown in Figure 1. Planktonic bacteria grow and multiply after landing on the material matrix, forming a bacterial biofilm. The surface of the biofilm is a layer of dense extracellular matrix. This layer of extracellular matrix has a solid structure and high strength. The bacteria wrapped inside are in close contact, which enhances the interaction and material exchange between bacteria, while preventing the entry of external damaging substances. Therefore, after biofilm is formed, it is not easily disturbed by antibiotics, preservatives and other external chemicals, so it is difficult to be removed by commonly used antibiotics.
Figure 1 The formation process of bacterial biofilm
The antibacterial mechanism of antibacterial titanium alloys can be divided into the following four steps: ① The antibacterial metal surface releases metal ions with antibacterial functions; ② Negatively charged bacterial cells and positively charged metal ions are attracted to each other, and the metal ions are absorbed into the bacteria ③ Metal ions destroy the cell wall and cell membrane of bacteria, or destroy their protein structure, causing the cytoplasm to leak; ④ Metal ions further penetrate the bacterial cell wall and combine with bacterial DNA, leading to bacterial denaturation and loss of replication ability. Whether it is damage to the cell wall or genetic material, the bacteria will die.
3. Research progress
3.1 Ti-Ag antibacterial titanium alloy
Silver (Ag), as an alloying element, can improve the corrosion resistance and mechanical properties of titanium-based metals. Takahashi et al. found that adding 20wt% Ag can improve the strength and wear resistance of cast titanium alloys while maintaining a high elongation. Shim et al. proved that Ti-Ag alloy has better corrosion resistance than pure titanium. Ag also has good biocompatibility, and Ag-Hg alloy has been used as a dental material. The excellent antibacterial properties of Ag-containing coatings have been confirmed by many studies. Therefore, by adding appropriate Ag to titanium and its alloys, it is possible to obtain Ag-containing titanium alloys with certain antibacterial properties. However, even though the Ag content in some Ti-Ag alloys is very high, even reaching 20wt%, they do not show significant antibacterial effects, indicating that the antibacterial effects of Ag-containing titanium alloys are not solely determined by the Ag content.
Zheng et al. added 2.9wt% Ag to TiNi shape memory alloy, and the cast TiNi alloy obtained showed certain antibacterial properties, and the antibacterial rate against Staphylococcus aureus reached 86.3%. Chen et al. used Ag powder with different contents and different particle sizes to sinter together with pure titanium powder to obtain a series of Ti-xAg alloys (x=1,3,5). Their mechanical properties, corrosion properties, antibacterial properties and in vitro cell phase The capacitance was characterized and evaluated. As shown in Figure 2, the antibacterial activity of the Ti-Ag alloy with an Ag particle size of 10 μm is higher than that of the Ti-Ag alloy with an Ag particle size of 75 μm. Contrary to the law of Ag ion release, the Ti-Ag alloy with an Ag particle size of 10 μm The ion release amount of the alloy is lower than that of the Ti-Ag alloy with an Ag powder particle size of 75 μm, indicating that the antibacterial performance of the Ti-Ag alloy should be closely related to the nano/micron-scale composite silver particles present on the matrix.
Figure 2 Bacterial colonies on the surface of pure Ti and Ti-Ag alloy
3.2 Ti-Cu antibacterial titanium alloy
In 2009, Shirai et al. first studied the antibacterial effect of Ti-xCu(x=1,5) alloy. The results showed that Ti-1Cu has significant antibacterial properties against E. coli and has good biological safety, opening up the gap between copper-containing bacteria and Titanium alloys serve as the curtain for medical metal material research. Subsequently, Zhang et al. used powder metallurgy to prepare Ti-10wt%Cu alloy, and studied the antibacterial properties, mechanical properties and corrosion properties of the alloy. As shown in Figure 3, Ti-10 Cu alloy is resistant to Staphylococcus aureus and Staphylococcus aureus. E. coli all have significant killing effects. The results of the intraosseous implantation test of Ti-10Cu alloy show that Ti-10Cu alloy has good bone cell compatibility. Further research results show that adding at least 5% Cu to titanium will have a significant antibacterial effect. For the purpose of antibacterial and anti-infection, the Institute of Metal Research, Chinese Academy of Sciences has developed a series of copper-containing titanium alloys with antibacterial functions, and has conducted a large number of in vitro and in vivo animal experimental research. The solid solubility of Cu in Ti is very low. When cooled from high temperature to 790°C, supersaturated Cu precipitates as a Ti2Cu intermetallic compound. The potential difference between it and the matrix will promote the alloy to release trace amounts of copper ions in a physiological environment. , thus exerting a strong bactericidal effect.
Figure 3 The killing effect of Ti-10Cu on Staphylococcus aureus and Escherichia coli
3.3 Ti6Al4V-Cu antibacterial titanium alloy
Peng et al. conducted comprehensive performance optimization on the thermally processed Ti6Al4V-xCu (x=4.5, 6, 7.5) alloy. The research results show that in order to obtain the best mechanical properties, corrosion resistance and wear resistance of the alloy, the optimal heat treatment processes after thermal processing of the three groups of alloys are to hold at 720°C, 740°C and 760°C for 1 hour and then air-cool. In Figure 4, they are represented by 4.5Cu-720, 6Cu-740 and 7.5Cu-760 respectively. The antibacterial test and cytotoxicity test results of the three groups of alloys are shown in Figure 4. From Figure 4(a)-(d), it can be seen that there are more bacterial colonies after co-culture with Ti6Al4V alloy, and after co-culture with Ti6A14V-Cu alloy The number of bacterial colonies is small, indicating that the copper-containing titanium alloy has strong antibacterial properties. Figure 4(e) shows the antibacterial rate of Ti6Al4V-xCu alloy. It can be seen that the antibacterial rate of the 4.5Cu-720 sample is about 80%. As the Cu content increases, the antibacterial rate of the alloy increases slightly, indicating that the antibacterial performance has improved. As can be seen from Figure 4(f), when co-cultured with cells for 1 and 3 days, the absorbance values of Ti6A14V-Cu alloy and Ti6A14V alloy are not much different; but at 7 days, the value of 7.5Cu-760 is significantly lower than that of Ti6A14V alloy, indicating that It has certain cytotoxicity at 7 days. It can be seen that for Ti6A14V-xCu alloy, the Cu content should not be higher than 6%, otherwise the alloy will show a certain degree of cytotoxicity after a long time.
Figure 4 Ti6A14V (a) 4.5Cu-720; (b) 6Cu-740; (c) 7.5Cu-760; (d) Bacterial growth morphology after alloy co-culture; (e) Comparison of antibacterial rates of Ti6Al4V alloy; (f) Absorbance values of cells co-cultured with different alloys for 1, 3 and 7 days
