Papers by Author: Tadashi Kokubo

Abstract: Alumina powder containing δ , δ crystal phases (designated δAP) showed osteoconductivity. δAP was manufactured by fusing pulverized alumina powder and quenching it. The purpose of the present study was to evaluate osteoconductivity of δAP using rat tibiae. Alumina powder containing αcrystal phase (designated αAP) was used as a reference material. These two types of alumina powder were packed into the intramedullary canals of rat tibiae to evaluate osteoconductivity, as determined by an affinity index. Rats were sacrificed at 4 and 8 weeks after surgery. The affinity index, equal to the length of bone in direct contact with the powder surface expressed as a percentage of the total length of the powder surface, was calculated for each alumina powder at each interval. At 4 and 8 weeks, the affinity indices for δAP were significantly higher than those for αAP. For both δAP and αAP, there were no significant differences between the values for 4 and 8 weeks. This study revealed that the osteoconductivity of δAP was due to the alumina’s δcrystal phases. δAP shows promise as a basis for developing a osteoconductive biomaterial.

Abstract: Bioactive polymeric microspheres can be produced by pre-coating them with a calcium silicate solution and the subsequent soaking in a simulated body fluid (SBF). Such combination should allow for the development of bioactive microspheres for several applications in the medical field including tissue engineering. In this work, three types of polymeric microspheres with different sizes were used: (i) ethylene-vinyl alcohol co-polymer (20-30 'm), (ii) polyamide 12 (10-30 'm) and (iii) polyamide 12 (300 'm). These microspheres were soaked in a calcium silicate solution at 36.5°C for different periods of time under several conditions. Afterwards, they were dried in air at 100°C for 24 hrs. Then, the samples were soaked in SBF for 1, 3 and 7 days. Fourier transformed infrared spectroscopy, thin-film X-ray diffraction, and scanning electron microscopy showed that after the calcium silicate treatment and the subsequent soaking in SBF, the microspheres successfully formed a bonelike apatite layer on their surfaces in SBF within 7 days due to the formation of silanol (Si-OH) groups that are quite effective for apatite formation.

Abstract: Sulfonic groups (-SO3H) were covalently attached on different polymeric surfaces enabling them to induce apatite nucleation, for developing bioactive apatite-polymer composites with a bonelike 3-dimensional structure. High molecular weight polyethylene (HMWPE) and ethylene-co-vinyl alcohol co-polymer (EVOH) were used. The polymers were soaked in two types of sulphate-containing solutions with different concentrations, sulphuric acid (H2SO4) and chlorosulfonic acid (ClSO3H). To incorporate calcium ions into to the sulfonated polymers, the samples were soaked in a saturated Ca(OH)2 solution for 24 hours. After soaking of the samples in a simulated body fluid (SBF), formation of an apatite layer on both surfaces was observed. The results obtained prove the validity of the proposed concept and show that the -SO3H groups are effective on inducing apatite nucleation on the surface of these polymers.

Abstract: The nano-composite of a ceria-stabilized tetragonal zirconia polycrystals (Ce-TZP) and alumina (Al2O3) polycrystals (Ce-TZP/Al2O3) is attractive as a load-bearing bone substitute because of its mechanical properties and phase stability. We have developed a new method of hydrofluoric acid and heat treatment (HFT) to give a microporous structure to the surface of this Ce-TZP/Al2O3 nanocomposite ceramic. Bone-bonding ability of a microporous surface and calcium phosphate coating on Ce-TZP/Al2O3 composite has been investigated through in vivo detaching model. Thin calcium phosphate coating layer was added by alternate soaking process, and thick CaP layer was produced by soaking in simulated body fluid for 5 days. HFT treated Ce-TZP/Al2O3 composite showed high bone-bonding ability compared with the control group. Thick and thin CaP coating accelerated bone-bonding ability in early post-implantation period. The submicron microporous surface was beneficial for achieving mechanical interlocking between the ceramic and surrounding bone. These results suggest the possibility of using a Ce-TZP/Al2O3 nanocomposite ceramic with microporous surface and calcium phosphate coating as the bearing material for uncemented total joint replacements.

Abstract: Ethylene-vinyl alcohol copolymer (EVOH), poly(ethylene terephthalate) (PET) and polyethylene (PE) were modified with calcium silicate on their surfaces by a sol-gel method, before or after glow discharge treatment in O2 gas, soaked in a simulated body fluid (SBF) and implanted into knee bone of a rabbit. EVOH and PET formed nano-sized bonelike apatite uniformly on their surfaces in SBF, without being subjected to the glow discharge, and bonded to the living bone of the rabbit, whereas PE formed the apatite only sparsely even when being subjected to the glow discharge. Three dimensional fabrics with open spaces in various sizes of the former fibers modified with the calcium silicate might be useful as bone substitutes.

Abstract: Porous bioactive titanium implant was produced by plasma-spray method and succeeding chemical and thermal treatment. This porous titanium implant possess a porosity of 40% and complex interconnective porous structure. Mechanical property of porous titanium was characterized for compressive and 4-point bending properties, as well as compressive fatigue. Bone tissue response and biocompatibility of porous bioactive titanium implant was evaluated by in vivo osteoconductive model. Ultimate compression strength and bending strength were 280 and 101 MPa. Bone ingrowth showed significant increases in treated implant, while in these untreated porous titanium implant, bone ingrowth seemed to decrease with time. These results suggest that porous bioactive titanium is a candidate for clinical applications under load-bearing conditions.

Abstract: A new bioactive bone cement (cGBC) consisting of crystallized MgO-CaO-SiO2-P2O5 glass beads and high-molecular-weight polymethyl methacrylate (hPMMA) has been developed to overcome the degradation seen with a previously reported cement (GBC) consisting of MgO-CaO-SiO2-P2O5-CaF2 glass beads and hPMMA. The purpose of the present study was to evaluate the degradation of cGBC using an in vivo aging test, and to compare the degradation of cGBC with that of GBC. Hardened rectangular specimens (20x4x3mm) were prepared from both cements. Their initial bending strengths were measured using the three-point bending method. GBC and cGBC specimens were then implanted into the dorsal subcutaneous tissue of rats, removed after 6 or 12 months, and tested for bending strength. The initial bending strengths (MPa) of GBC and cGBC were 141.9±1.8 and 144.4±2.4, respectively, while at 6 months they were 109.1±2.6 and 114.1±4.9, and at 12 months they were 109.1±3.2 and 113.1±3.3, respectively. Although the difference in initial bending strengths was not significant, the bending strength of cGBC was significantly higher than that of GBC at 6 and 12 months, indicating that cGBC is more resistant to cement degradation. The bending strengths of both GBC and cGBC decreased significantly from 0 to 6 months but did not change significantly thereafter. Thus, degradation of cGBC and GBC does not appear to continue after 6 months. We believe that cGBC and GBC are strong enough for use under weight-bearing conditions and that their mechanical strength (especially that of cGBC) is retained in vivo.

Abstract: Two types of new bioactive polymethylmethacrylate (PMMA)-based bone cements containing nano−sized titania (TiO2) particles were prepared and evaluated to assess the effect of TiO2 content on their mechanical properties and osteoconductivity. We prepared two types of bioactive bone cement, ST50c and ST60c, which contained 50 wt% silanized TiO2 and 60 wt% silanized TiO2, respectively. Commercially available PMMA cement (PMMAc) was used as a control. The cements were inserted into rat tibiae and solidified in situ. After 6 and 12 weeks, they were taken out for evaluation of osteoconductivity by scanning electron microscopy (SEM), contact microradiography (CMR) and Giemsa surface staining. SEM revealed that ST60c and ST50c apposed to bone directly while PMMAc did not. The affinity index of ST60c was significantly higher than for the other cements at each time interval. The results showed that ST60c was a promising material, but its mechanical strength should be improved before application in prosthesis fixation.

Abstract: In this study, we examined in vivo performance of newly developed hydroxyapatite (HA)ceramics, which is obtained by sintering the HA powder mixed with CaO·MgO·SiO2-based glass at 1000°C (liquid phase sintering). Bioactivity of this glass-containing HA was evaluated compared with the control HA by mechanical test and histological examination. The glass-containing HA showed higher bone-bonding strength than the control HA throughout the experimental period. Light microscope and backscattered scanning electron microscope (SEM) showed that the both kinds of implants bonded directly to the bone. High bioactivity in vivo, especially in the early period after implantation, of this newly developed HA was confirmed, which is one of the essential requirement for optimal bone substitutes.