Papers by Author: Chikara Ohtsuki

Abstract: Natural bone has excellent mechanical properties such as high fracture toughness and high flexibility. These properties are achieved by specific microstructure of natural bone that is composed of the organic collagen and inorganic apatite. On the basis of these findings, apatite-polymer hybrids are expected as novel bone substitutes having excellent mehcanical performances and high bone-bonding ability, i.e. bioactivity. In this study, we attempted preparation of apatite-polyglutamic acid hybrids through biomimetic process that mimics the principle of biomineralization. Simple chemical modification of the polyglutamic acid gel with 1 M (= mol/L) calcium chloride solution provided the gel with apatite-forming ability in simulated body fluid (SBF, Kokubo solution). This type of hybrid is also useful for designing bioactive bone substitutes with injectability, since viscosity of the polyglutamic acid gel can be easily controlled according to degree of cross-linking.

Abstract: Organic-inorganic hybrids composed of organic polymer and apatite is quite attractive as novel bone-repairing materials since it has mechanical performance analogous to those of natural bone as well as bone-bonding ability, i.e. bioactivity. To fabricate such an apatite-polymer hybrid, biomimetic process has been recently paid much attention. In this process, bone-like apatite is deposited on the surfaces of organic substrates in simulated body fluid (SBF, Kokubo solution) having ion concentrations analogous to those of human extracellular fluid or more concentrated solutions. Previous studies showed that the apatite deposition is triggered by a catalytic effect of carboxyl groups (COOH) on the surfaces of the organic substrates. In this study, we examined apatite deposition on natural polypeptides derived from crops in a biomimetic solution. We selected gluten derived from wheat and zein derived from corn. Both of gluten and zein formed bone-like apatite on their surfaces in a solution that has inorganic ion concentrations 1.5 times those of simulated body fluid, when they were treated with 1 mol/L calcium chloride solution. High content of acidic amino acids such as glutamic acid and aspartic acid in gluten and zein would give large amount of carboxyl groups effective for the apatite nucleation.

Abstract: Organic polymers with ability of apatite formation in body environment are expected as novel bone substitutes having not only bone-bonding ability, i.e. bioactivity, but also mechanical performance analogous to natural bone. Several metal oxides have been found to be effective for the apatite deposition in body environment. In addition, release of calcium ions from the materials significantly enhances it. In this study, we attempted to synthesize bioactive organic-inorganic hybrids from poly(vinyl alcohol) (PVA) by incorporation of titanium oxide or zirconium oxide as well as calcium salt. Ability of apatite formation on the hybrids was examined in vitro using simulated body fluid (SBF, Kokubo solution). Apatite deposition was observed to occur on the surfaces of PVA/titanium oxide hybrids in SBF, when their compositions were appropriately controlled.

Abstract: Our previous study presented that sericin, a kind of silk protein, had high ability of apatite formation under a condition mimicking body environment when the sericin contains high content of β sheet structure. To confirm the effectiveness of β sheet structure on apatite nucleation, we attempted to synthesize of polypeptide containing β sheet structure and investigate apatite formation in 1.5SBF that has 1.5 times the inorganic ion concentrations of human blood plasma. Poly(FEFEFEFG) was synthesized as the polypeptide consisting mainly of β sheet structure. Formation of hydroxyapatite was observed on the film of the poly(FEFEFEFG) after soaking in 1.5SBF within 7 days. We could confirm that β sheet structure was effective even in the synthetic polypeptide.

Abstract: Apatite formation on polyamide films containing either carboxyl or sulfonic groups was compared in 1.5SBF, whose ion concentrations are 1.5 times those of a simulated body fluid (SBF). The sulfonic groups induced the apatite nucleation earlier than the carboxyl groups. In contrast, the rate of crystal growth depended not on the kind of functional group, but on the degree of supersaturation of the surrounding solution. The more ready association of sulfonic groups with calcium ions may lead to earlier apatite nucleation than that of carboxyl groups. Adhesive strength of the apatite layer to polyamide film containing sulfonic groups was significantly lower than that with carboxyl groups depending on the chemical interactions as well as on the mechanical properties of the polyamide film.

Abstract: In order to overcome the disadvantage of commercialized PMMA bone cement, we have developed novel PMMA-based bone cement(7P3S) reinforced by 30 wt.% of bioactive CaO-SiO2 gel powders to induce the bioactivity as well as to increase mechanical property for the PMMA bone cement. The novel 7P3S bone cement hardened after mixing for about 7 minutes. For in vitro evaluation, apatite forming ability of it was investigated using SBF. When the novel 7P3S bone cement was soaked into SBF, it formed apatite on its surfaces within 1 week Furthermore; there is no decrease in its compressive strength within 9 weeks soaking in SBF. It is though that hardly decrease in compressive strength of 7P3S bone cement in SBF is due to the relative small amount of gel powder or its spherical shape and monosize. In vivo evaluation of the novel 7P3S bone cement was carried out using rabbit. After implantion into rabbit tibia for several periods, the interface between novel bone cement and natural bone was evaluated by CT images. According to the results, the novel bone cement directly contact to the natural bone without fibrous tissue after implantation for 4 weeks. This results indicates that the newly developed 7P3S bone cement can bond to the living bone and also be effectively used as bioactive bone cement without decrease in mechanical property.

Abstract: Tricalcium phosphate (3CaO⋅P2O5, TCP) is known as a biodegradable material and already used clinically as important bone-repairing materials. However, the control of its bone-bonding ability, i.e. bioactivity, and biodegradability is not easy. On the other hand, diopside (CaO⋅MgO⋅2SiO2) ceramic shows a potential of direct contact with bone and high mechanical strength, but low biodegradability. We expected that a glass-ceramic containing TCP and diopside show high bioactivity and high mechanical strength, as well as biodegradability. Glasses with composition x(3CaO⋅P2O5)⋅(100-x) (CaO⋅MgO⋅2SiO2) (x = 0, 38, 50, 60 mass%) were prepared. They were pulverized and the compacts of the resultant powders were heated to obtain the glass-ceramics. Only diopside was precipitated at x = 0 in the glass composition, whitlockite (β-TCP) and diopside were at x = 38, 50 and 60, when the compacts were sintered at 1200 °C. The prepared glass-ceramics formed apatite on their surfaces in a simulated body fluid (SBF). This indicates that these glass-ceramics have a potential to show bioactivity.

Abstract: CaO-SiO2 gels for bioactive organic-inorganic composites were prepared from tetraethoxysilane (TEOS) and calcium nitrate tetrahydrate (Ca(NO3)2⋅4H2O) by a sol-gel method with the addition of polyethylene glycol (PEG) and methacryloxypropyltrimethoxysilane (MPS). The effects of PEG and MPS on morphology and bioactivity of the gel were investigated. The samples with the nominal compositions of Ca(NO3)2:TEOS:MPS = 30:70:0 and 30:63:7 (in molar ratio) were prepared with or without coexistence of PEG at a molar ratio of (TEOS+MPS):PEG = 70:0.16. Spherical powders were obtained regardless of the addition of MPS after removal of PEG by washing, whereas the samples prepared without PEG gave crack-free bulk bodies. Incorporation of MPS was confirmed form the results of Fourier transform infrared spectroscopy (FT-IR). All the samples, regardless of addition of PEG and MPS, formed apatite on their surfaces in simulated body fluid (SBF), when washing time was 3 h during the preparation. These results show that the bioactive spherical powder of CaO-SiO2 gel modified with MPS can be obtained by the present method. It is expected to induce the increase of the chemical bonding with surrounding organic matrix when it was used as fillers for composite materials.

Abstract: The feasibility of processing glass-ceramics using the layer manufacturing technique, selective laser sintering (SLS), to produce parts with suitable biological and mechanical properties for use in bone replacement applications, has been investigated. Glass-ceramics derived from glasses based on several different systems have been considered. Initial experiments using an apatite-mullite glass-ceramic (4.5SiO2⋅3Al203⋅1.6P2O5⋅3CaO⋅2CaF2) demonstrated the ability to process glass-ceramic materials using this technique, creating parts with a strength similar to that of cancellous bone, and a porous structure that was shown in vivo to be suitable for the ingrowth of bone. Concerns over the inability of the apatite-mullite material to form an apatite layer on its surface when soaked in a simulated body fluid (SBF) has led to the development of Al2O3-free glasses based on the systems (50-x)CaO⋅45SiO2⋅5P2O5⋅xCaF2 and (48-x)CaO⋅45SiO2⋅5P2O5⋅2CaF2⋅xNa2O. These materials have demonstrated good in vitro bioactivity, and therefore have good potential as candidates for processing by an indirect SLS method for the production of custom-made bone implants.

Abstract: Apatite formation behavior of tricalcium phosphate (TCP) ceramics with different phases and porosity was investigated in a simulated body fluid (SBF, Kokubo solution). The pure α-TCP with 80% porosity did not form hydroxyapatite (HAp) on its surface after soaking in SBF for 7 days. On the other hand, the pure α-TCP with 20% porosity formed HAp on its surface after soaking in SBF within 7 days, and the biphasic TCP, which consisted of mixture of α-TCP and β-TCP and had 20% porosity, formed HAp within 1 day. The low porosity and coexistence of α-TCP and β-TCP phases in TCP ceramics were effective for apatite formation in SBF.