Papers by Author: Tadashi Kokubo

Abstract: Pedicle screw (PS) system using Ti-6Al-4V PSs became popular in spinal instrumentation system. However, they sometimes case loosening and back-out from bone because of their poor bone-bonding ability. In the present study, Ti-6Al-4V alloy was subjected to the acid-heat or calcium-heat treatments that are effective for inducing high capacities of apatite formation and bone bonding on pure Ti. When the alloy was subjected to the acid-heat treatment, a surface layer composed of rutile and anatase TiO₂ enriched with Al and V was produced. Thus the treated alloy was neutrally charged and did not form apatite in a simulated body fluid (SBF) even after 3 day. In contrast, when the alloy was subjected to the Ca-heat treatment, a surface layer composed of calcium titanate, anatase and rutile free from Al and V was produced. The treated alloy formed apatite in SBF within 3 days. When the Ti-6Al-4V PSs subjected to the Ca-heat treatment was implanted into vertebra of beagle dogs, they showed higher bone-bonding ability as well as bone contact area than those without the treatment. This kind of bioactive Ti-6Al-4V PSs might be useful for spinal instrumentation since they could prevent loosening and back-out from bone.

Abstract: The purpose of this research is to form a layer of alumina on Ti-6Al-4V alloy for hip joint by deposition of Al layer on the Ti alloy and its subsequent oxidation. In this work, a thick layer of Al was deposited onto the Ti alloy by cold spraying. The reaction layer of Al₃Ti was formed by heat treatment of cold sprayed Al at 640°C in air/Ar atmosphere to ensure a good adhesion between cold sprayed Al layer and the Ti alloy. A thick Al₃Ti layer formed by heat treatment of Al layer at 640°C for 12 h in air, was subjected to heat treatment at 850°C for 96 h in air to form a-alumina and Al₂Ti. Thus, alumina scales can be formed on the top surface of the Ti alloy and can be densified by increasing the time duration of heat treatment.

Abstract: Various kinds of materials have been found to bond to living bone and some of them are clinically used as important bone substitutes. However, they can not be used under load-bearing conditions, since their fracture toughness are not so high as that of human cortical bone. All of them are based on calcium phosphate or silicate. The present authors recently showed that even Ti metal and its alloys having high fracture toughness can show bone-bonding bioactivity, if they are subjected to simple chemical and heat treatments to form some kind of titanium oxide or titanates on their surfaces. They can show not only bone-bonding property, but also novel functions such as osteoinduction, release of antibacterial or bone-growth promoting ions etc.

Abstract: 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.

Abstract: Preparation of bioactive titanium (Ti) metal able to release Zn²⁺ ions was attempted by chemical and heat treatments of Ti metal. Ti metal was soaked in 5M NaOH solution at 60 °C to form sodium hydrogen titanate (SHT) on its surface. Then, it was soaked in a mixed solution of 100 mM Ca(CH₃COO)₂ and 0.01 - 1 mM Zn (CH₃COO)₂ at 40 °C for 24 h to replace Na⁺ ions in SHT with Ca²⁺ and Zn²⁺ ions at given range of 0.15 to 2.95 in Zn/Ca ratio. When it was heat-treated at 600 °C for 1 h, zinc-incorporated calcium titanate (ZCT) and rutile were formed on the surface of Ti metal. The ZCT partially replaced its Ca²⁺ and Zn²⁺ ions with H₃O⁺ ions by subsequent soaking in 1 mM acetic acid solution at 80 °C. Thus treated Ti metal formed apatite on its surface in a simulated body fluid (SBF) within 3 days, and slowly released Zn²⁺ ions into phosphate-buffered solution (PBS) up to 0.03 ppm. The Ti metal formed with this kind of bioactive ZCT layer on its surface is expected to be useful as orthopedic and dental implants, since it could bond to living bone sooner, by promoting formation of the surrounding bone.

Abstract: Ti-15Zr-4Nb-4Ta alloy is an attractive metal for orthopaedic implants, since it is free from cytotoxic elements and shows high mechanical strength. It was recently shown by an animal experiment [1] that this alloy tightly bonds to living bone, when it was subjected to 5 M NaOH solution and 100 mM CaCl₂ solution treatments, heat treatment at 600 or 700 °C, and final water treatment at 80 °C. The bonding strength was increased markedly when the heat treatment temperature was increased from 600 to 700 °C. This increase of the bonding strength was attributed to the increase in apatite-forming ability of the treated alloy in a simulated body fluid (SBF) [2] with ion concentrations nearly equal to human blood plasma, although its reason was not revealed yet.

Abstract: We previously found that a positively charged Ti metal has a higher apatite forming ability in vitro than a non-charged Ti metal. For in vivo analysis using a rabbit model, two types of Ti metal were examined: porous Ti metals heat-treated subsequent to a mixed acid treatment (MHs) and porous Ti metals not heat-treated subsequent to the same mixed acid treatment (MOs). Although MHs and MOs had the same macro- and micro-structure, they had different surface charges. MHs, considered positively charged, had significantly higher bone ingrowth than MOs, considered charged zero. Similarly, MHs had significantly higher percentages of bone–implant contact than MOs at 3- and 6-week. A simple heat treatment made acid-treated porous titanium implants more osteoconductive. These results suggest that a positive charge obtained by a heat treatment enhances bioactivity of acid-treated titanium implants.

Abstract: Surface structural change of titanium metal with NaOH and heat treatments and the subsequent soaking in a simulated body fluid (SBF) was investigated by observing cross section of its surface layer by scanning electron microscope. A layer of lathlike phase of sodium hydrogen titanate was formed on the surface of the titanium metal 1 µm in thickness by the NaOH treatment. This was transformed into a layer of lathlike form a little densified of sodium titanate and rutile by the subsequent heat treatment. In SBF, apatite started to precipitate in the interior of the surface lathlike layer, filled the interspaces of the lathlike phases and grew over the surface. This integration of the apatite with the surface lathlike layer might be responsible for the strong bonding of the titanium metal to the living bone.

Abstract: In a previous study, we have reported that sodium removal by dilute hydrochloric acid (HCl) converted the sodium titanate layer on the surface of an alkali-treated porous titanium into titania with a specific structure that has better bioactivity than sodium titanate. We have shown that a porous titanium with this treatment have good osteoinductivity in soft tissue of canines. In the present study, we investigated the effect of this treatment on the osteoconductive abilities of porous bioactive titanium implant in the long term. Three types of surface treatments were applied: (a) no treatment , (b) alkali, hot water, and heat treatment ( conventional treatment: W-AH treatment), and (c) alkali, dilute HCl, hot water, and heat treatment (Na-free treatment: HCl-AH treatment). We then examined the osteoconductivity of the materials implanted in the femoral condyles of Japanese white rabbits at 6, 12, 26, and 52 weeks. The results showed that the bone ingrowth in HCl-AH porous bioactive titanium was significantly higher than in W-AH porous bioactive titanium at 52 weeks. Therefore, sodium removal has a positive effect on the osteoconductivity of the porous bioactive titanium implant in the long term.

Abstract: It has been shown that titanium metal subjected to NaOH and heat treatments spontaneously forms a bonelike apatite on its surface in the living body and bonds to living bone. However, its apatite-forming ability was liable to decrease when the treated titanium metal was stored in humid environment. In the present study, the NaOH-treated titanium metal was soaked in a CaCl2 solution at 40°C for 24h, heat-treated at 600°C for 1h, and then soaked in ultrapure water at 80°C for 24h. Calcium titanate was formed on the surface of the titanium metal 1µm in thickness by these treatments. The resultant titanium metal showed high scratch resistance and high apatite-forming ability in a simulated body fluid. This high apatite-forming ability was maintained even after the titanium metal was kept in 95% relative humidity at 80°C for 1 week.