Tadashi Kokubo

Apatite-forming ability of titanium in terms of pH of the exposed solution

In order to elucidate the main factor governing the capacity for apatite formation of titanium (Ti), Ti was exposed to HCl or NaOH solutions with different pH values ranging from approximately 0 to 14 and then heat-treated at 600°C. Apatite formed on the metal surface in a simulated body fluid, when Ti was exposed to solutions with a pH less than 1.1 or higher than 13.6, while no apatite formed upon exposure to solutions with an intermediate pH value. The apatite formation on Ti exposed to strongly acidic or alkaline solutions is attributed to the magnitude of the positive or negative surface charge, respectively, while the absence of apatite formation at an intermediate pH is attributed to its neutral surface charge. The positive or negative surface charge was produced by the effect of either the acidic or alkaline ions on Ti, respectively. It is predicted from the present results that the bone bonding of Ti depends upon the pH of the solution to which it is exposed, i.e. Ti forms a bone-like apatite on its surface in the living body and bonds to living bone through the apatite layer upon heat treatment after exposure to a strongly acidic or alkaline solution.

Controlled release of strontium ions from a bioactive Ti metal with a Ca-enriched surface layer

A nanostructured sodium hydrogen titanate layer ∼1μm in thickness was initially produced on the surface of titanium metal (Ti) by soaking in NaOH solution. When the metal was subsequently soaked in a mixed solution of CaCl2 and SrCl2, its Na ions were replaced with Ca and Sr ions in an Sr/Ca ratio in the range 0.18-1.62. The metal was then heat-treated at 600°C to form strontium-containing calcium titanate (SrCT) and rutile on its surface. The treated metal did not form apatite in a simulated body fluid (SBF) even after 7days. When the metal formed with SrCT was subsequently soaked in water at 80°C, the treated metal formed bone-like apatite on its surface within 1day in SBF since the Ca ions were partially replaced with H3O(+) ions. However, it released only 0.06ppm of Sr ions even after 7days in phosphate-buffered saline. When the metal was soaked after the heat treatment in 1M SrCl2 solution instead of water, the treated metal released 0.92ppm of Sr ions within 7days while maintaining its apatite-forming ability. The Ti formed with this kind of bioactive SrCT layer on its surface is expected to be highly useful for orthopedic and dental implants, since it should be able to promote bone growth by releasing Sr ions and tightly bond to the bone through the apatite formed on its surface.

Osteoinduction on acid and heat treated porous Ti metal samples in canine muscle.

Samples of porous Ti metal were subjected to different acid and heat treatments. Ectopic bone formation on specimens embedded in dog muscle was compared with the surface characteristics of the specimen. Treatment of the specimens by H2SO4/HCl and heating at 600°C produced micrometer-scale roughness with surface layers composed of rutile phase of titanium dioxide. The acid- and heat-treated specimens induced ectopic bone formation within 6 months of implantation. A specimen treated using NaOH followed by HCl acid and then heat treatment produced nanometer-scale surface roughness with a surface layer composed of both rutile and anatase phases of titanium dioxide. These specimens also induced bone formation after 6 months of implantation. Both these specimens featured positive surface charge and good apatite-forming abilities in a simulated body fluid. The amount of the bone induced in the porous structure increased with apatite-forming ability and higher positive surface charge. Untreated porous Ti metal samples showed no bone formation even after 12 months. Specimens that were only heat treated featured a smooth surface composed of rutile. A mixed acid treatment produced specimens with micrometer-scale rough surfaces composed of titanium hydride. Both of them also showed no bone formation after 12 months. The specimens that showed no bone formation also featured almost zero surface charge and no apatite-forming ability. These results indicate that osteoinduction of these porous Ti metal samples is directly related to positive surface charge that facilitates formation of apatite on the metal surfaces in vitro.

Formation of a bioactive calcium titanate layer on gum metal by chemical treatment

The so-called gum metal with the composition Ti–36Nb–2Ta–3Zr–0.3O is free from cytotoxic elements and exhibits a low elastic modulus as well as high mechanical strength. In the present study, it was shown that this alloy exhibited a high capacity for apatite formation in a simulated body fluid when subjected to 1xa0M NaOH treatment, 100xa0mM CaCl2 treatment, heat treatment at 700°C, and then hot water treatment. The high apatite formation was attributed to the CaTi2O5 which was precipitated on its surface, and found to be maintained even in a humid environment over a long period. The treated surface exhibited high scratch resistance, which is likely to be useful in clinical applications. The surface treatment had little effect on the unique mechanical properties described above. These results show that gum metal subjected to the present surface treatments exhibits a high potential for bone-bonding, which will be useful in orthopedic and dental implants.

Bone-bonding properties of Ti metal subjected to acid and heat treatments

The effects of surface treatment on the bone-bonding properties of Ti metal were examined by both mechanical detaching test and histological observation after implantation into rabbit tibiae for various periods ranging fromxa04 toxa026xa0weeks. The bone-bonding ability of Ti metal, which is extremely low as it is abraded, was hardly increased by simple heat treatment at 600xa0°C or treatment with H2SO4/HCl mixed acid alone, but was markedly increased by the heat treatment after the acid treatment. Even Ti metal that had been previously subjected to NaOH treatment showed considerably high bone-bonding ability after acid and heat treatments. Such high bonding abilities were attributed to their high apatite-forming ability in the body environment. Their high apatite-forming abilities were attributed to a high positive surface charge, and not to the type of crystalline phase or specific roughness of their surfaces. The present study has demonstrated that acid and subsequent heat treatments are effective for conferring stable fixation properties on Ti metal implants.

Osteoconduction of porous Ti metal enhanced by acid and heat treatments

Bone ingrowth into porous Ti metal is important for stable fixation of Ti metal implants to surrounding bone. However, without surface treatment this is limited to only a thin region of the outer surface of the Ti metal. In the present study, a porous Ti metal with a porosity of ~60xa0% and interpore connections of 70–200 micrometers in diameter was investigated in terms of its chemical and heat treatments, by implanting it into rabbit femur for periods varying from 3 to 12xa0weeks. The porous Ti metal subjected to heat treatment at 600xa0°C after H2SO4/HCl mixed acid treatment showed the largest bone ingrowth in comparison with those subjected to no treatment, only acid treatment, and only heat treatment even at an early stage after implantation, and remained as such even 12xa0weeks after implantation. Their bone ingrowths were well interpreted in terms of apatite-forming abilities of the Ti metals in body environment. Their apatite-forming abilities did not depend upon their surface roughness nor type of crystalline phase, but upon the positive surface charge.

A bioactive Ti metal with a Ca-enriched surface layer releases Mg ions

A bioactive surface layer that released Mg2+ ions was produced on the surface of titanium metal (Ti) by chemical and heat treatments. Ti was soaked in 5 M NaOH solution at 60 °C for 24 h to form sodium hydrogen titanate (SHT) on its surface. Then, it was soaked in a mixed solution of 100−X mM CaCl2 and X mM MgCl2 (X represents a range from 20 to 80) at 40 °C for 24 h to replace Na+ ions in the SHT with Ca2+ and Mg2+ ions in a range of 0.10 to 0.93 in Mg/Ca ratio. When the metal with a 0.43 in Mg/Ca ratio on its surface was heat-treated at 600 °C for 1 h, magnesium-containing calcium titanate (MCT), anatase and rutile formed on the Ti surface. When the metal formed with MCT was subsequently soaked in water or 1 M MgCl2 solution at 80 °C for 24 h, the Ca2+ and Mg2+ ions in MCT were partially replaced with H3O+ ions. Thus, the treated metal released 0.02 or 0.43 ppm of Mg2+ ions within 7 days in 2 ml of phosphate buffered saline and formed bone-like apatite on its surface within 1 day in a simulated body fluid. The Ti formed with this kind of bioactive MCT layer on its surface is expected to be useful for orthopedic and dental implants, since it should be able to promote bone growth by releasing Mg2+ ions and tightly bond to the bone through the apatite formed on its surface.

Bone bonding ability of a chemically and thermally treated low elastic modulus Ti alloy: gum metal.

The gum metal with composition Ti–36Nb–2Ta–3Zr–0.3O, is free from cytotoxic elements and exhibits a low elastic modulus as well as high mechanical strength. We have previously demonstrated that this gum metal, once subjected to a series of surface treatments—immersion in 1xa0M NaOH (alkali treatment) and then 100xa0mM CaCl2, before heating at 700xa0°C (sample: ACaH-GM), with an optional final hot water immersion (sample: ACaHW-GM)—has apatite-forming ability in simulated body fluid. To confirm the in vivo bioactivity of these treated alloys, failure loads between implants and bone at 4, 8, 16, and 26xa0weeks after implantation in rabbits’ tibiae were measured for untreated gum metal (UT-GM), ACaH-GM and ACaHW-GM, as well as pure titanium plates after alkali and heat treatment (AH-Ti). The ACaH-GM and UT-GM plates showed almost no bonding, whereas ACaHW-GM and AH-Ti plates showed successful bonding by 4xa0weeks, and their failure loads subsequently increased with time. The histological findings showed a large amount of new bone in contact with the surface of ACaHW-GM and AH-Ti plates, suggesting that the ACaHW treatment could impart bone-bonding bioactivity to a gum metal in vivo. Thus, with this improved bioactive treatment, these advantageous gum metals become useful candidates for orthopedic and dental devices.

Effect of Ca contamination on apatite formation in a Ti metal subjected to NaOH and heat treatments

It has long been known that titanium (Ti) metal bonds to living bone through an apatite layer formed on its surface in the living body after it had previously been subjected to NaOH and heat treatments and as a result had formed sodium titanate on its surface. These treatments were applied to a porous Ti metal layer on a total hip joint and the resultant joint has been in clinical use since 2007. It has been also demonstrated that the apatite formation on the treated Ti metal in the living body also occurred in an acelullar simulated body fluid (SBF) with ion concentrations nearly equal to those of the human blood plasma, and hence bone-bonding ability of the treated Ti metal can be evaluated using SBF in vitro. However, it was recently found that certain Ti metals subjected to the same NaOH and heat treatments display apatite formation in SBF which is decreased with the increasing volume of the NaOH solution used in some cases. This indicates that bone-bonding ability of the treated Ti metal varies with the volume of the NaOH solution used. In the present study, this phenomenon was systematically investigated using commercial NaOH reagents and is considered in terms of the structure and composition of the surface layers of the treated Ti metals. It was found that a larger amount of the calcium contamination in the NaOH reagent is concentrated on the surface of the Ti metal during the NaOH treatment with an increasing volume of the NaOH solution, and that this inhibited apatite formation on the Ti metal in SBF by suppressing Na ion release from the sodium titanate into the surrounding fluid. Even a Ca contamination level of 0.0005xa0% of the NaOH reagent was sufficient to inhibit apatite formation. On the other hand, another NaOH reagent with a nominal purity of just 97xa0% did not exhibit any such inhibition, since it contained almost no Ca contamination. This indicates that NaOH reagent must be carefully selected for obtaining reliable bone-bonding implants of Ti metal by the NaOH and heat treatments.

Bioactive Ti Metal with Ca-Enriched Surface Layer Able to Release Sr Ions

Bioactive Ti metal able to release Sr ions was prepared by chemical and heat treatments of Ti metal. Ti metal was initially soaked in 5M NaOH solution to form sodium hydrogen titanate. It was soaked in a mixed solution of CaCl2 and SrCl2 to replace its Na ions with Ca and Sr ions at a given range from 0.18 to 1.62 in Sr/Ca ratio. When it was heat-treated at 600 oC, it formed Sr-containing calcium titanate (SrCT) and rutile. The apatite formation in SBF of the treated metal was low, but increased markedly by subsequently soaking the metal in 1 M SrCl2 solution at 80 oC. Thus, the treated metal gradually released Sr ions into phosphate-buffered saline up to 0.9 ppm. It is expected that the Ti metal formed with the bioactive SrCT layer could release Sr ions in a living body to promote bone formation, and bond to a living bone through an apatite.