Papers by Author: Tadashi Kokubo

Abstract: Titanium has limitations in its clinical performance in dental and orthopaedic applications. Over the last decade, numerous implant surface modifications have been developed and are currently used with the aim of enhancing bone integration. In the present study, we have experimented a bioactive titanium prepared by a simple chemical and moderate heat treatment that leads to the formation of a bone-like apatite layer on its surface in simulated body fluids. We haved used foetal rat calvaria cell cultures to investigate bone nodule formation on bioactive titanium. Scanning electron microscopy (SEM) showed that cells attached and spread on the bioactive surfaces. After 22 days of culture, bone nodules were detected on the material surface. Furthermore, the mineralized bone nodules remained attached to the bioactive titanium surface but not to untreated titanium. SEM observations and EDX microanalysis of sectioned squares showed that bone-like tissue directly bonded to bioactive titanium, but not pure titanium. These results indicated the importance of the implant surface composition in supporting differentiation of osteogenic cells and the subsequent apposition of bone matrix allowing a strong bond to bone. Furthermore, these findings may provide promising strategies for the development of biologically active implants.

Abstract: Tantalum metal was soaked in NaOH and CaCl2 solutions, and then subjected to heat treatment at 500°C. EDX analysis showed that about 6.5 at. % of Na was incorporated into the surface of the tantalum metal by the first NaOH treatment. These Na+ ions were replaced by Ca2+ ions by the subsequent CaCl2 treatment. According to TF-XRD patterns, an amorphous sodium tantalate was seemed to be formed on the tantalum metal by the NaOH treatment and transformed into amorphous calcium tantalate by the CaCl2 treatment. This phase was crystallized into Ca2Ta2O7 by heat treatment. Critical detaching load of the surface of the CaCl2-treated tantalum metal was as low as 5mN, while as high as 42mN after the heat treatment. Apatite-forming ability of the NaOH-treated tantalum metal in a simulated body fluid (SBF) was appreciably increased by the CaCl2 treatment and maintained even after the heat treatment.

Abstract: In order to study method for preparing bioactive titanium metal, calcium ions were attempted to be incorporated into the surface of the titanium metal by ion exchange method. Titanium metal was soaked in 5M NaOH solution and 100mMCaCl2 solution and subjected to heat treatment. About 5 atom% of Na was incorporated into the surface of the titanium metal by the NaOH treatment This Na was completely replaced with calcium ion by the CaCl2 treatment and maintained even after the heat treatment. Critical detaching strength of the surface layer to the substrate of NaOH-treated titanium metal was a little increased by the CaCl2 treatment and remarkably increased by the heat treatment. Apatite-forming ability of the NaOH-treated titanium metal in SBF was increased by the CaCl2 treatment, but decreased by the subsequent heat treatment.

Abstract: We have developed a porous titanium implant sintered with spacer particles (porosity = 50 %, average pore size ± standard deviation = 303 ± 152 !m, yield compression strength = 100MPa). This porous titanium was successfully treated with chemical and thermal treatment that gives a bioactive micro-porous titania layer on the titanium surface, and it is expected as effective biomaterial for biological fixation on load bearing condition. In this study, ten adult female beagle dogs underwent anterior lumbar interbody fusion at L6-7 using either BT-implant or non-treated implant (NT-implant), then followed by posterior interspinous wiring and facet screw fixation. The radiographic evaluations were performed 1, 2 and 3 months postoperatively using X-ray fluoroscopy. Animals were sacrificed after 3 months postoperatively, and fusion status was evaluated by manual palpation. Histological evaluation was also performed. Both histological and radiological evaluation revealed that interbody fusion was achieved in 5 of 5 dogs (100%) in BT-group and 3 of 5 dogs (60%) in NT-group. In BT implants, we could observe a large amount of new bone formation from periphery to the center of the implant, whereas in NT implants, fibrous tissue formation was still observed even in the implants with successful fusion. The results of this study indicate that porous bioactive titanium implant will represent a new osteoconductive biomaterial with improved fusion characteristics.

Abstract: A porous structure comprises pores and pore throats with a complex three-dimensional 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. Bioactive porous titanium implants with 48% porosity were analyzed using specific algorithms for three-dimensional analysis of interconnectivity based on a micro focus X-ray computed tomography system. In vivo histological analysis was performed using the very same implants implanted into the femoral condyles of male rabbits for 6 weeks. This matching study revealed that more poorly differentiated pores tended to have narrow pore throats, especially in their shorter routes to the outside. Data obtained suggest that this sort of novel analysis is useful for evaluating bone and tissue ingrowth into porous biomaterials.

Abstract: The aim of this study was to optimize the surface treatment and to accelerate the osteoinductivity of porous bioactive titanium implant. Previous studies have reported that sodium removal with hot water treatment converts sodium titanate on the surface of an alkali-treated titanium plate into titania with a specific structure, which has better bioactivity than sodium titanate. 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, (b) alkali, hot water, and heat treatment (conventional treatment), and (c) alkali, dilute HCl, hot water, and heat treatment (Na-free treatment). The osteoinductivity of the materials implanted in the back muscles of adult beagle dogs was examined at three, six, and twelve months. Na-free porous bioactive titanium exhibited the highest osteoinductivity, and bone formation was observed within three months. This study showed that sodium removal has a significant positive effect on the osteoinductivity of the porous bioactive titanium implant.

Abstract: Chemically durable microspheres 20−30 µm in diameter containing a large amount of yttrium are useful for in situ radiotherapy of cancer as they can be activated by neutron bombardment to become β-emitters and can be injected in the vicinity of the cancer to provide a large localized dose of β-radiation. In this study, preparation of hollow Y2O3 microspheres using an enzymatic reaction was attempted, and the structure and chemical durability of the resulting microspheres were investigated. Hollow Y2O3 microspheres 20–30 &m in diameter were successfully prepared by this enzymatic method. The outer surface of the microspheres was smooth and dense, whereas the inner parts had a honeycombed structure. In simulated body fluids at pH 6 and 7, the hollow Y2O3 microspheres showed high chemical durability.

Abstract: Generally, characterizations of pore structures of porous biomaterials are mainly based on 2-dimensional (2-D) analysis using cross sectional micrographs. However, interconnectivity of each pore may be more important factor, when tissue ingrowth into deeper pores is considered. In this paper, using micro-CT imaging with 3-D image processing software, analyses of porous material based on 3-demensional (3-D) geometrical considerations were successfully performed. Plasmasprayed porous titanium implant (PT) and four types of sintered porous titanium implants (ST50- 200, ST50-500, ST70-200, and ST70-500) that possess different porosities (50% and 70%) and pore sizes (200-500+m and 500-1500+m) were analyzed in this study. A micro focus X-ray computed tomography system was employed to acquire microstructural information from the porous implants. Using 3-D image processing software, we performed three types of 3-D analysis including detection of the dead space (% dead pore), analysis of interconnectivity by blocking the narrow pore throat with caliber less than 52 +m (% pore with narrow throat) and analysis of material construct by contracting thin strut with thickness less than 52 +m (% construct with thin strut). ST50S and ST50L possessed interconnected porous structure with thicker strut; however, pore throat was considered to be relatively narrow. On the other hand, PT implant possesses favorable interconnectivity despite its’ low porosity; however, relatively thin strut indicate the structural disadvantage for mechanical property. These results suggest that the 3-D analysis of pore and strut structure using micro focus X-ray computed tomography and 3-D image processing software will provide effective information to develop porous implant.

Abstract: Bioactive bone cement with mechanical properties higher than that of commercial polymethylmethacrylate (PMMA) bone cement are strongly desired to be developed. In the present study, PMMA-based cement incorporated with nano-sized rutile particles was prepared. The PMMA-based cement (rutile content was 50 wt%) shows the compressive strength (136 MPa) higher than that of commercial PMMA bone cement (88 MPa). The hardened cement formed apatite on the surface in a simulated body fluid within 3 days. Therefore, this PMMA-based cement incorporated with rutile particles might be useful as cement for fixation of prostheses as well as self-setting bone substitutes, because of its high apatite forming ability and mechanical strength.

Abstract: Three types of polymethylmethacrylate (PMMA)-based composite cements containing 40− 56 wt% micron-sized titania (titanium oxide) particles, designated ST2-40c, ST2-50c, and ST2-56c, were developed as bone substitutes for vertebroplasty, and evaluated for their mechanical, setting, and biological properties. In animal experiments, ST2-50c and ST2-56c were implanted into rat tibiae and solidified in situ. Their biological properties were evaluated at 6 and 12 weeks after implantation. Compressive strength, bending strength, and bending modulus increased with increasing titania content. Peak temperature during the setting reaction decreased as the filler content increased. ST2-56c had direct contact with bone over larger areas than ST2-50c at 6 and 12 weeks. Data from the present study indicated that ST2-56c is a good candidate as a bone substitute for vertebroplasty.