Biomedical subjects

Tadashi Kokubo

Publications and source records attributed to Tadashi Kokubo.

At least 19 recordsLinked to original sources

PubMed2006

Pore throat size and connectivity determine bone and tissue ingrowth into porous implants: three-dimensional micro-CT based structural analyses of porous bioactive titanium implants.

A porous structure comprises pores and pore throats with a complex three-dimensional (3D) network structure, and many investigators have described the relationship between average pore size and the amount of bone ingrowth. However, the influence of network structure or pore throats for tissue ingrowth has rarely been discussed. Four types of bioactive porous titanium implants with different pore sizes and porosities (6mm in diameter and 15 mm long) were analyzed using specific algorithms for 3D analysis of interconnectivity based on a micro focus X-ray computed tomography system. In vivo histomorphometric analysis was performed using the very same implants implanted into the femoral condyles of male rabbits for 6 and 12 weeks. This matching study revealed that more poorly differentiated pores tended to have narrow pore throats, especially in their shorter routes to the outside. In addition, for assessment of the entire implant, we proposed new two indices that represent the degree of bone and tissue ingrowth into an implant by considering the effect of narrow pore throats. Data obtained suggest that this sort of novel analysis is useful for evaluating bone and tissue ingrowth into porous biomaterials.

Algorithms↗

PubMed2006

Accelerated degradation and improved bone-bonding ability of hydroxyapatite ceramics by the addition of glass.

Dense hydroxyapatite (HA) ceramics are useful bone substitutes, but they degrade minimally. One solution is to incorporate degradable materials in the HA. In this study, we manufactured glass-containing HA and investigated whether the degradability and bone-bonding ability of the HA were improved. The glass-containing HA was manufactured from a mixture of HA powder and 1.0 wt% glass powder. The control HA was manufactured from pure HA powder. In vitro degradability was evaluated by soaking in physiological saline, and a rabbit model was used to evaluate in vivo degradability and bone-bonding ability. Detaching tests were performed for all removed samples to quantify bone-bonding ability of each type of HA. The glass-containing HA showed higher degradability than the control HA, both in vitro and in vivo. The detaching failure load of the glass-containing HA was rapidly elevated after implantation and was higher than that of the control HA. Our results suggest that the dissolution of the added glass made the glass-containing HA degradable and that the detaching failure load of the glass-containing HA was elevated by reinforcement of the mechanical locking at the roughened interface. Incorporation of glass additives into HA can be concluded to be a good candidate for producing a bone substitute that can partially degrade and bond to bone firmly and rapidly.

Absorbable Implants↗

PubMed2006

How useful is SBF in predicting in vivo bone bioactivity?

The bone-bonding ability of a material is often evaluated by examining the ability of apatite to form on its surface in a simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma. However, the validity of this method for evaluating bone-bonding ability has not been assessed systematically. Here, the history of SBF, correlation of the ability of apatite to form on various materials in SBF with their in vivo bone bioactivities, and some examples of the development of novel bioactive materials based on apatite formation in SBF are reviewed. It was concluded that examination of apatite formation on a material in SBF is useful for predicting the in vivo bone bioactivity of a material, and the number of animals used in and the duration of animal experiments can be reduced remarkably by using this method.

Animals↗

PubMed2006

Osteoinductive porous titanium implants: effect of sodium removal by dilute HCl treatment.

In a previous study, we observed that chemically and thermally treated plasma-sprayed porous titanium possesses intrinsic osteoinductivity and that bone formation occurs after 12 months in the muscles of beagle dogs. The aim of this study was to optimize the surface treatment and to accelerate the osteoinductivity. Previous studies have reported that sodium removal converts the sodium titanate layer on the surface of an alkali-treated titanium plate into a more bioactive titania layer. In this study, we developed a dilute hydrochloric acid (HCl) treatment for porous titanium, which removed sodium from the complexly shaped porous structure more effectively than conventional hot water treatment. Three types of surface treatments were applied: (a) alkali and heat treatment (AH treatment); (b) alkali, hot water, and heat treatment (Water-AH treatment); and (c) alkali, dilute HCl, hot water, and heat treatment (HCl-AH treatment). The osteoinductivity of the materials implanted in the back muscles of adult beagle dogs was examined at 3, 6, and 12 months. The HCl-AH-treated porous bioactive titanium implant had the highest osteoinductivity, with induction of a large amount of bone formation within 3 months. The dilute HCl treatment was considered to give both chemical (titania formation and sodium removal) and topographic (etching) effects on the titanium surface, although we cannot determine which is the predominant factor. Nevertheless, adding the dilute HCl treatment to the conventional chemical and thermal treatments is a promising candidate for advanced surface treatment of porous titanium implants.

Animals↗

PubMed2006

Enzymatic preparation of hollow magnetite microspheres for hyperthermic treatment of cancer.

Ferrimagnetic materials can be expected to be useful as thermal seeds for hyperthermic treatment of cancer, especially where the cancer is located in deep parts of body, as they can generate heat by magnetic hysteretic loss when they are placed in an alternating magnetic field. In this study, hollow magnetite (Fe(3)O(4)) particles were prepared using an enzymatic reaction of urease. A hollow particle was obtained by using a Pasteur pipette. The particle was 500 microm in size and was composed of Fe(3)O(4). Its saturation magnetization and coercive force were 57 emuxg(-1) and 183 Oe, respectively. Its heat generation under an alternating magnetic field of 300 Oe at 100 kHz was estimated to be 45 Wxg(-1). Microspheres 30 microm in diameter were also successfully obtained by using a spray gun.

Biocompatible Materials↗

PubMed2005

Formation of bone-like apatite on organic polymers treated with a silane-coupling agent and a titania solution.

Polyethylene terephthalate (PET), ethylene-vinyl alcohol copolymer (EVOH) and Nylon 6 in plate form were treated with silane-coupling agents, a titanium alkoxide-alcohol solution and a hot HCl solution to form a thin crystalline titanium oxide layer. When placed in a simulated body fluid with ion concentrations nearly equal to those of the human blood plasma, nanosized bone-like apatite formed uniformly on the surfaces of these treated polymers: within 2 days for PET and Nylon 6, and 7 days for EVOH. This indicates that such titania-modified polymers might form bone-like apatite in the living body, and bond to living bone through this apatite layer. Three-dimensional fabrics of these polymer fibers, with open spaces in various sizes, are expected to be useful as bone substitutes, as they will be integrated with the natural bone.

Apatites↗

PubMed2005

Preparation of ferrimagnetic magnetite microspheres for in situ hyperthermic treatment of cancer.

Ferrimagnetic microspheres 20-30 microm in diameter are useful as thermoseeds for inducing hyperthermia in cancers, especially for tumors located deep inside the body. The microspheres are entrapped in the capillary bed of the tumors when they are implanted through blood vessels and heat cancers locally by their hysteresis loss when placed under an alternating magnetic field. In the present study, preparation of magnetite (Fe(3)O(4)) microspheres 20-30 microm in diameter was attempted by melting powders in high-frequency induction thermal plasma, and by precipitation from aqueous solution. The microspheres prepared by melting powders in high-frequency induction thermal plasma were composed of a large amount of Fe(3)O(4) and a small amount of wustite (FeO), and those subsequently heat treated at 600 degrees C for 1 h under 5.1 x 10(3) Pa were fully composed of Fe(3)O(4) 1 microm in size. The saturation magnetization and coercive force of the heat-treated microspheres were 92 emu g(-1) and 50 Oe, respectively. The heat generation of the heat-treated microspheres was estimated to be 10 Wg(-1), under 300 Oe and 100 kHz. The microspheres prepared by precipitation from aqueous solution consisted of beta-FeOOH, and those subsequently heat treated at 400 degrees C for 1 h in a 70% CO(2) + 30% H(2) atmosphere consisted of Fe(3)O(4) crystals 50 nm in size. The saturation magnetization and coercive force of the heat-treated microspheres were 53 emu g(-1) and 156 Oe, respectively. The heat generation of the heat-treated microspheres was estimated to be 41 Wg(-1), under 300 Oe and 100 kHz. The latter microspheres are believed to be promising thermoseeds for hyperthermic treatment of cancer.

Animals↗

PubMed2005

Process and kinetics of bonelike apatite formation on sintered hydroxyapatite in a simulated body fluid.

The surfaces of two hydroxyapatites (HA), which have been sintered at different temperatures of 800 and 1200 degrees C, was investigated as a function of soaking time in simulated body fluid (SBF) using transmission electron microscopy (TEM) attached with energy-dispersive spectrometry (EDX) and laser electrophoresis spectroscopy. The TEM-EDX indicated that after soaking in SBF, both the HAs form bonelike apatite by undergoing the same surface structural change, i.e., formations of a Ca-rich amorphous or nano-crystalline calcium phosphate (ACP) and a Ca-poor ACP, which eventually crystallized into bonelike apatite. Zeta potential characterized by the electrophoresis indicated that during exposure to SBF, the HA surfaces reveal negative surface charge, thereby interacting with the positive calcium ions in the fluid to form the Ca-rich ACP, which gains positive surface charge. The Ca-rich ACP on the HAs then interacts with the negative phosphate ions in the fluid to form the Ca-poor ACP, which stabilizes by being crystallized into bonelike apatite with a low solubility in the SBF. The exposure times for formations of these phases of the Ca-rich ACP, the Ca-poor ACP as well as the apatite were, however, all late on HA sintered at 1200 degrees C, compared with the HA sintered at 800 degrees C. This phenomenon was attributed to a lower initial negative surface charge of the HA sintered at 800 degrees C than of that one sintered at 1200 degrees C, owing to poverty in surface hydroxyl and phosphate groups which are responsible for the surface negativity of the HA. These indicate that sintered temperature of HA might influence not in terms of the process but in terms of the rate of formation of biologically active bonelike apatite on its surface, through which the HA integrates with living bone.

Apatites↗

PubMed2005

Mechanical properties and osteoconductivity of porous bioactive titanium.

Porous bioactive titanium implants (porosity of 40%) were produced by a plasma-spray method and subsequent chemical and thermal treatments of immersion in a 5M aqueous NaOH solution at 60 degrees C for 24 h, immersion in distilled water at 40 degrees C for 48 h, and heating to 600 degrees C for 1 h. Compression strength and bending strength were 280 MPa (0.2% offset yield strength 85.2 MPa) and 101 MPa, respectively. For in vivo analysis, bioactive and nontreated porous titanium cylinders were implanted into 6mm diameter holes in rabbit femoral condyles. The percentage of bone-implant contact (affinity index) of the bioactive implants (BGs) was significantly larger than for the nontreated implants (CGs) at all postimplantation times (13.5 versus 10.5, 16.7 versus 12.7, 17.7 versus 10.2, 19.1 versus 7.8 at 2, 4, 8 and 16 weeks, respectively). The percentage of bone area ingrowth showed a significant increase with the BGs, whereas with the CGs it appeared to decrease after 4 weeks (10.7 versus 9.9, 12.3 versus 13.1, 15.2 versus 9.8, 20.6 versus 8.7 at 2, 4, 8 and 16 weeks, respectively). These results suggest that porous bioactive titanium has sufficient mechanical properties and biocompatibility for clinical use under load-bearing conditions.

Animals↗

PubMed2004

In vivo aging test for a bioactive bone cement consisting of glass bead filler and PMMA matrix.

The degradation of a new bioactive bone cement (GBC), comprised of an inorganic filler (bioactive MgO-CaO-SiO(2)-P(2)O(5)-CaF(2) glass beads) and an organic matrix [high-molecular-weight polymethyl methacrylate (PMMA)], was evaluated in an in vivo aging test. Hardened rectangular specimens (20 x 4 x 3 mm) were prepared from two GBC formulations (containing 50% w/w [GBC50] or 60% w/w [GBC60] bioactive beads) and a conventional PMMA bone cement control (CMW-1). Initial bending strengths were measured with the use of the three-point bending method. Specimens of all three cements were then implanted into the dorsal subcutaneous tissue of rats, removed after 3, 6, or 12 months, and tested for bending strength. The bending strengths (MPa) of GBC50 at baseline (0 months), 3, 6, and 12 months were 136 +/- 1, 119 +/- 3, 106 +/- 5 and 104 +/- 5, respectively. Corresponding values were 138 +/- 3, 120 +/- 3, 110 +/- 2 and 109 +/- 5 for GBC60, and 106 +/- 5, 97 +/- 5, 92 +/- 4 and 88 +/- 4 for CMW-1. Although the bending strengths of all three cements decreased significantly from 0 to 6 months, those of GBC50 and GBC60 did not change significantly thereafter, whereas that of CMW-1 declined significantly between 6 and 12 months. Thus, degradation of GBC50 and GBC60 does not appear to continue after 6 months, whereas CMW-1 degrades progressively over 12 months. Moreover, the bending strengths of GBC50 and GBC60 (especially GBC60) were significantly higher than that of CMW-1 throughout. It is believed that GBC60 is strong enough for use under weight-bearing conditions and that its mechanical strength is retained in vivo; however, its dynamic fatigue behavior will need assessment before application in the clinical setting.

Animals↗

PubMed2004

Apatite formation on non-woven fabric of carboxymethylated chitin in SBF.

Chitin fibres constituting a non-woven fabric were carboxymethylated in monochloro acetic acid and treated with saturated Ca(OH)(2) aqueous solution. Within 3 days in a simulated body fluid with pH value and ion concentrations nearly equal to those of human blood plasma, a bonelike apatite layer formed on the surface of fibres of the treated fabric. The apatite-chitin fibre composite thus prepared is expected to be useful as a flexible bioactive bone-repairing material.

Adsorption↗

PubMed2004

Apatite-forming ability and mechanical properties of PTMO-modified CaO-SiO2-TiO2 hybrids derived from sol-gel processing.

Hydrolysis and polycondensation of triethoxysilane end-capped Poly (tetramethylene oxide) (Si-PTMO), tetraethoxysilane (TEOS), tetraisopropyltitanate (TiPT) and calcium nitrate (Ca(NO(3))(2)) gave transparent monolithics of PTMO-modified CaO-SiO(2)-TiO(2) hybrids. The samples with (TiPT)/(TEOS+TiPT) molar ratios from 0 to 0.20 under constant ratio of (Si-PTMO)/(TEOS+TiPT) of 2/3 in weight were prepared. It was found that the incorporation of TiO(2) component into a PTMO-CaO-SiO(2) hybrid results in an increase in the apatite-forming ability in a simulated body fluid: the hybrids with (TiPT)/(TEOS+TiPT) of 0.10 and 0.20 in mol formed an apatite on their surfaces within only 0.5 day. It seemed that, within the range of compositions studied, the TiO(2) content little affects the overall mechanical properties: Young's modulus were 52-55MPa, tensile strength, 7-9MPa, and strain at failure, about 30%. Thus, the organic-inorganic hybrids exhibiting both fairly high apatite-forming ability and high capability for deformation were obtained. These hybrid materials may be useful as new kind of bioactive bone-repairing materials.

Body Fluids↗

PubMed2004

Osteoinduction of porous bioactive titanium metal.

This is the first report of bone induction in a non-osseous site by titanium metal, which has long been recognized as a non-bioactive material. After undergoing specific chemical and thermal treatments, porous bioactive titanium induced bone formation without the need of additional osteogenic cells or osteoinductive agents. Four types of titanium implants were implanted in the dorsal muscles of mature beagle dogs, and were examined histologically after periods of 3 and 12 months. Chemically and thermally treated titanium, as well as pure titanium, was implanted either as porous blocks or as fibre mesh cylinders. Bone formation was found only in the chemically and thermally treated porous block implants removed after 12 months. The present study shows that even a non-soluble metal that contains no calcium or phosphorus can be an osteoinductive material when treated to form an appropriate macrostructure and microstructure. This finding may elucidate the nature of osteoinduction, and lead to the advent of epochal osteoinductive biomaterials for tissue regeneration.

Animals↗

PubMed2004

Preparation of bioactive titanium metal via anodic oxidation treatment.

Titania with specific structures of anatase and rutile was found to induce apatite formation in vitro. In this study, anodic oxidation in H(2)SO(4) solution, which could form anatase and rutile on titanium metal surface by conditioning the process, was employed to modify the structure and bioactivity of biomedical titanium. After the titanium metal was subjected to anodic oxidation treatment, thin film X-ray diffraction and scanning electron microscopy results showed the titanium metals surfaces were covered by porous titania of anatase and/or rutile. In simulated body fluid (SBF), the titanium anodically oxidized under the conditions with spark-discharge could induce apatite formation on its surface. The induction period of apatite formation was decreased with increasing amount of either anatase or rutile by conditioning the anodic oxidation. After the titanium metal, anodically oxidized under the conditions without spark-discharge, was subjected to heat treatment at 600 degrees C for 1 h, it could also induce apatite formation in SBF because the amount of anatase and/or rutile was increased by the heat treatment. Our results showed that induction of apatite-forming ability on titanium metal could be attained by anodic oxidation conjoined with heat treatment. So it was believed that anodic oxidation in H(2)SO(4) solution was an effective way to prepare bioactive titanium.

Apatites↗

PubMed2003

Surface potential change in bioactive titanium metal during the process of apatite formation in simulated body fluid.

Bioactive titanium metal can be prepared by NaOH and heat treatments that present the metal with a graded bioactive surface layer of amorphous sodium titanate. This study used laser electrophoresis together with transmission electron microscopy (TEM) and energy-dispersive X-ray microanalysis (EDX) to relate the surface potential change of the bioactive titanium metal with its surface structural change in simulated body fluid (SBF). The surface potential of the metal was highly negative immediately after immersion in SBF. With increasing soaking time, the surface potential increased, revealing a maximum positive value, and then decreased to a constant negative value. TEM-EDX showed that immediately after immersion in SBF, the metal surface formed Ti-OH groups by exchanging Na(+) ions in the surface sodium titanate with H3O(+) ions in the fluid. Thereafter, with increasing soaking time the metal surface formed an amorphous calcium titanate, then an amorphous calcium phosphate, and, finally, apatite with bone-like composition and structure. These results indicate that the process of apatite formation on bioactive titanium metal is initiated by the formation of Ti-OH groups with negative charges that interact with calcium ions with positive charges to form calcium titanate. The calcium titanate gains a positive charge and later interacts with phosphate ions with negative charges, forming amorphous calcium phosphate. The amorphous calcium phosphate eventually transforms and stabilizes into bone-like crystalline apatite with a negative charge.

Apatites↗

PubMed2003

Phase stability after aging and its influence on pin-on-disk wear properties of Ce-TZP/Al2O3 nanocomposite and conventional Y-TZP.

Recently zirconia/alumina composites have been examined by many researchers as the new generation of bearing materials in total joint replacements. In this study, the phase stability of a Ce-TZP/Al(2)O(3) nanocomposite and conventional Y-TZP after aging, and its influence on wear resistance, were investigated. Very slight phase transformation was observed in both types of ceramics 18 months after the implantation of Ce-TZP/Al(2)O(3) or Y-TZP samples into rabbit tibiae. However, Y-TZP showed marked phase transformation (approximately 80%) after aging in an autoclave (121 degrees C) for 190 h or in physiological saline at 62 degrees C for 18 months, whereas the new composite remained almost resistant to degradation. According to the results of self-pairing pin-on-disk wear tests using ceramic specimens with or without autoclave aging, the wear factor was almost the same between Ce-TZP/Al(2)O(3) samples with and without aging (6.74 +/- 0.36 x 10(-8) and 6.04 +/- 0.95 x 10(-8) mm(3)/Nm, respectively). In contrast, although non-aged Y-TZP had the lowest wear factor (4.88 +/- 0.51 x 10(-8) mm(3)/Nm) of all specimens tested, aged Y-TZP showed 10-fold greater wear than nonaged Y-TZP. The present study suggests that Ce-TZP/Al(2)O(3) nanocomposite has much greater phase stability than Y-TZP, and that its wear properties are not influenced by aging.

Aluminum Oxide↗

PubMed2003

Biology of alkali- and heat-treated titanium implants.

In cementless fixation systems, surface character is an important factor. Alkali and heat treatments of titanium metal have been shown to produce strong bonding to bone and a higher ongrowth rate. In this study we examined the effect of alkali and heat treatments on titanium rods in an intramedullary rabbit femur model, in regard to the cementless hip stem. The implant rods were 5 mm in diameter and 25 mm in length. Half of the implants were immersed in 5 mol/L sodium hydroxide solution and heated at 600 degrees C for 1 h (AH implants), and the other half were untreated (CL implants). The rods were implanted into the distal femur of the rabbits; AH implants into the left femur and CL implants into the right. The bone-implant interfaces were evaluated at 3, 6, and 12 weeks after implantation. Pull-out tests showed that the AH implants had a significantly higher bonding strength to bone than the CL implants at each time point. As postoperative time elapsed, histological examination revealed that new bone formed on the surface of both types of implants, but significantly more bone made direct contact with the surface of the AH implants. At 12 weeks, approximately 56% of the whole surface of the AH implants was covered with the bone. In conclusion, alkali- and heat-treated titanium offers strong bone bonding and a high affinity to bone as opposed to a conventional mechanical interlocking mechanism. Alkali and heat treatments of titanium may be suitable surface treatments for cementless joint replacement implants.

Animals↗

PubMed2003

Preparation of antibacterial silver-doped silica glass microspheres.

Various types of inorganic substances doped with silver ions have been developed as antibacterial materials, and some have already been commercialized. Colorless and chemically durable materials that slowly release silver ions are, however, still need to be developed. The present authors have previously shown that when a silica glass doped with silver and aluminium ions is prepared using the sol-gel method, the resultant product is colorless, chemically durable, and slowly releases silver ions into water over a long period. The doped silica glass takes a form of microspheres <1 microm in diameter, it is easily mixed with organic polymers, and the mixture can be formed into a thin film or fine fibers, etc. We report on the preparation of silver doped silica glass microspheres having a diameter =1 microm, using the sol-gel method. Initially, tetraethoxysilane was partially prehydrolyzed by water in ethanol, and then aluminium triisopropoxide was added to the solution to form Si-O-Al bonds. Finally, an ammonia solution containing silver nitrate was added to form silica microspheres doped with silver ion together with aluminium ions. The results show monodispersed microspheres 0.4-0.6 microm in diameter were obtained with nominal compositions of Si/Al/Ag = 1/0.01-0.03/0.003-0.03, with a molar ratio of Al/Ag = 1-3.3. The microspheres were colorless, showed a high chemical durability, and slowly released silver ions into water at 37 degrees C. Microspheres with the composition Si/Al/Ag = 1/0.01/0.01 showed excellent antibacterial activity against Escherichia coli. The minimum inhibitory concentration (MIC) of the microspheres was 400, which is less than the MIC value (800) of commercial antibacterial materials.

Anti-Bacterial Agents↗