Abstract: The materials for the repair of bone defects require bone-inductive and bioabsorbable properties. We developed an apatite-coated hyaluronan (ACH) as a bone-regeneration material. To examine the initial behavior of osteoblast-like cells on ACH and its bone-inductive activity, we evaluated the proliferation and differentiation of osteoblast-like cells grown on ACH in vitro, and examined the effect of ACH on bone regeneration in vivo, comparing these with the effects of an atelocollagen sponge (AS). Hyaluronic acid, cross-linked by divinylsulfone, was freeze-dried and formed apatite in simulated body fluid. MC3T3-E1 osteoblast-like cells were cultured on ACH and AS. Alkaline phosphatase activity and osteocalcin mRNA expression increased more in cells grown on ACH than in those grown on AS. In vivo, round defects were created in rat crania and either filled with ACH or AS or left unfilled (sham group). After surgery, the ACH-treated group showed higher levels of bone formation than the other groups. These findings demonstrate that ACH is more effective than AS in promoting in vitro osteoblast-like cell differentiation and bone formation during the repair of bone defects in vivo, indicating that it may be of use in the treatment of various bone defects.
Abstract: Chemically durable microspheres containing yttrium and/or phosphorus are useful for intra-arterial radiotherapy. In this study, we attempted to prepare yttrium phosphate (YPO₄) microspheres with high chemical durability. YPO₄ microspheres with smooth surfaces and diameters of around 25 μm were successfully obtained when gelatin droplets containing yttrium and phosphate ions were cooled and solidified in a water-in-oil emulsion and then heat-treated at 1100°C. The chemical durability of the heat-treated microspheres in a simulated body fluid at pH = 6 and 7 was high enough for clinical application of intra-arterial radiotherapy.
Abstract: The formation of hydroxyapatite is important for artificial materials to show high biological affinities for bone tissue. The present study focused on the synthesis of hydrogels capable of showing apatite formation, through modification of polyglutamic acid (PGA) with 3-aminopropyltriethoxysilane (APTES), followed by treatment with calcium chloride solution. A transparent bulk hydrogel was obtained at a molar ratio of PGA/APTES of 0.5. Prior soaking of the PGA hydrogel in calcium chloride solution accelerated the formation of bone-like apatite in a simulated body fluid. The modified PGA hydrogel is a candidate material for a biodegradable scaffold for bone regeneration.
Abstract: Porous Y2O3 microparticles 500 microm in size were obtained, when 1 wt%-ammonium alginate aqueous solution was dropped into 0.5 M-YCl3 aqueous solution by a Pasteur pipette and the resultant gel microparticles were heat-treated at 1100 degrees C. Small pores less than 1 microm were formed in the microparticles by the heat treatment. The bulk density of the heat-treated microparticle was as low as 0.66 g cm(-3). The chemical durability of the heat-treated microparticles in simulated body fluid at pH = 6 and 7 was high enough for clinical application of in situ radiotherapy. Although the size of the microparticles should be decreased to around 25 microm using atomizing device such as spray gun for clinical application, we found that the porous Y2O3 microparticles with high chemical durability and low density can be obtained by utilizing gelation of ammonium alginate in YCl3 aqueous solution in this study.
Abstract: Bioactive ceramics have been used clinically to repair bone defects owing to their biological affinity to living bone; i.e. the capability of direct bonding to living bone, their so-called bioactivity. However, currently available bioactive ceramics do not satisfy every clinical application. Therefore, the development of novel design of bioactive materials is necessary. Bioactive ceramics show osteoconduction by formation of biologically active bone-like apatite through chemical reaction of the ceramic surface with surrounding body fluid. Hence, the control of their chemical reactivity in body fluid is essential to developing novel bioactive materials as well as biodegradable materials. This paper reviews novel bioactive materials designed based on chemical reactivity in body fluid.
Abstract: The objective of this study was to investigate whether the in vivo osteoinductive activity of an implant material is enhanced by covering the surface of apatite with incorporated bone morphogenetic protein 2 (BMP-2) and heparin which maintains the activity of BMP-2.
Abstract: Various calcium phosphates are used for bone repair. Although hydroxyapatite (HA) sintered ceramics are widely used due to their osteoconductivity, its bioresorbability is so low that HA remains in the body for a long time after implantation. In contrast, tricalcium phosphate (TCP) ceramics show resorbable characters during bone regeneration, and can be completely substituted for the bone tissue after stimulation of bone formation. Therefore, much attention is paid to TCP ceramics for scaffold materials for supporting bone regeneration. This paper reviews bioresorbable properties of calcium phosphate ceramics derived from beta-TCP and alpha-TCP.
Abstract: Bone morphogenetic proteins (BMPs) strongly induce osteogenesis and are enhanced by heparin. In this study, a potent osteoinductive material was developed by coating the surface of titanium with apatite incorporated with BMP and heparin.
Abstract: Organic-inorganic composites, prepared from bone-bonding bioactive ceramics and organic polymers, are useful for novel bone substitutes having mechanical properties analogous to natural bone. We synthesized composites from cellulose and carbonate hydroxyapatite (CHAp) in situ through mechanochemical reaction. They contained B-type CHAp analogous to bone apatite. They showed a bending strengths of 10-13 MPa and Young's modulus of 1.5-2.2 GPa. We predicted their microstructure by comparing the measured density with the theoretical one. Cellulose was assumed to be distributed in the pore of CHAp at low cellulose content, and in grain boundaries of CHAp at high cellulose content. The composites formed calcium phosphate on their surfaces in simulated body fluid, meaning that they have a potential to be bioactive.
Abstract: A simulated body fluid (SBF) with ion concentrations approximately equal to those of human blood plasma has been used widely for in vitro assessment of the bioactivity of artificial materials and for the formation of bone-like apatite on various substrates. The ion concentrations of a conventional SBF (c-SBF) are, however, not exactly equal to those of blood plasma. In the present study, a revision of c-SBF was made to prepare new SBFs (r-SBF, i-SBF, and m-SBF) with ion concentrations equal to or closer to those of blood plasma. The ion concentrations of the r-SBF and i-SBF were designed to be equal to those of blood plasma in total and dissociated amounts, respectively. The m-SBF was designed to have a total ion concentration equal to that of blood plasma, except for the concentration of HCO(-) (3), which was set to the saturated level with respect to calcite. The ion concentrations and pH of the as-prepared new SBFs were found to be equal to those of the nominal values. Upon sealed storage, the r-SBF and i-SBF showed no change in ion concentrations for up to 4 weeks at 5 degrees C, and up to 2 weeks at 36.5 degrees C, but thereafter they showed a decrease in HCO(-) (3) concentration and an increase in pH. Under the same storage conditions, the c-SBF and m-SBF showed no change in ion concentrations and pH values over a period of up to 8 weeks. These results indicate that the r-SBF and i-SBF are less stable than the c-SBF and m-SBF in terms of changes in ion concentrations relative to storage period. The m-SBF is optimal for in vitro bioactivity assessment of artificial materials and for biomimetic production of bone-like apatite.
Abstract: Tantalum metal is a candidate for use as an implant material in high load-bearing bony defects, due to its attractive features such as high fracture toughness and high workability. This metal, however, does not have bone-bonding ability, i.e. bioactivity, and therefore the development of bioactive tantalum metal is highly desirable. It is known that the essential prerequisite for an artificial material to show bioactivity is to form a bonelike apatite layer on its surface in the body environment. The same type of apatite layer is formed in a simulated body fluid (SBF) with inorganic ion concentrations nearly equal to those of human blood plasma. The present authors previously showed that the apatite formation on tantalum metal in SBF was remarkably accelerated by treatment with 0.5 M-NaOH aqueous solution and subsequent firing at 300 degrees C, while untreated tantalum metal spontaneously formed the same apatite after a long soaking period. In the present study, the bonding strength of the apatite layer to the substrate was quantitatively evaluated in comparison with that to the untreated tantalum metal. Adhesive strength was measured as an estimation of bonding strength, and the surface microstructure of both the substrates was characterized in order to discuss the difference in the bonding strength in terms of surface structure. The apatite layer formed on the NaOH- and heat-treated tantalum metal shows higher adhesive strength than that formed on the untreated metal. The amorphous sodium tantalate layer formed on the tantalum metal by NaOH and heat treatments, has a smooth graded structure where its concentration gradually changes from the surface into the interior metal. Smooth graded structure with complex of apatite is constructed after soaking in SBF. The higher bonding strength of the apatite layer formed on the treated metal is attributed to its smooth graded structure.
Abstract: The prerequisite for an artificial material to bond to living bone is the formation of bonelike apatite on its surface in the body. This apatite can be reproduced on its surface even in an acellular simulated body fluid with ion concentrations nearly equal to those of the human blood plasma. The present authors previously showed that the tantalum metal subjected to a NaOH treatment to form a sodium tantalate hydrogel layer on its surface forms the bonelike apatite on its surface in SBF in a short period. The gel layer as-formed on the metal is, however, not resistant against abrasion, and hence thus-treated metal is not useful for clinical applications. In the present study, effects of thermal treatment on the mechanical properties and apatite-forming ability of the NaOH-treated tantalum metal were investigated. The sodium tantalate gel on the NaOH-treated tantalum was dehydrated to convert into amorphous sodium tantalate by a thermal treatment at 300 degrees C in air environment and into crystalline sodium tantalates by the thermal treatment at 500 degrees C. Resistivity of the gel layer against both peeling-off and scratching was significantly improved by the thermal treatment at 300 degrees C. The high apatite-forming ability of the sodium tantalate hydrogel was a little decreased by the thermal treatment at 300 degrees C, but appreciably decreased by the thermal treatment at 500 degrees C. It is believed that the tantalum metal subjected to the 0.5 M-NaOH treatment and the subsequent thermal treatment at 300 degrees C is useful as implants in dental and orthopaedic fields, since it shows high bioactivity as well as high fracture toughness.
Abstract: Untreated tantalum metal formed an apatite on its surface in simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma. However, it took an induction period as long as 4 weeks for apatite formation. The tantalum metal formed the apatite within 1 week when it was previously soaked in a 0.2 or 0.5M NaOH aqueous solution at 60 degrees C for 24 h to form a sodium tantalate hydrogel layer on its surface. The decrease in the induction period of apatite formation was attributed to the catalytic effect of the Ta-OH groups on the surface of the tantalum metal for apatite nucleation and acceleration of the apatite nucleation by an increased ionic activity product of the apatite in the fluid due to the release of Na(+) ions. The NaOH-treated tantalum metal can form apatite in a short period even in the living body and bond to the bone through this apatite layer. This indicates that a highly bioactive tantalum metal can be obtained by a simple chemical treatment.
Abstract: Alkali- and heat-treated tantalum (Ta) has been shown to bond to bone. The purpose of this study was to investigate the effects of chemical treatments on the bone-bonding ability of tantalum implants in rabbit tibiae. Miyazaki et al. reported in vitro that alkali- and heat-treated tantalum had an apatite forming ability in an acellular simulated body fluid (SBF). In this study, smooth-surfaced rectangular plates (15 x 10 x 2 mm) of pure tantalum and treated tantalum were prepared. The plates were implanted transcortically into the proximal metaphyses of bilateral rabbit tibiae, alkali- and heat-treated plates for one limb and untreated plates for the contralateral limb, which served as a paired control. Bone bonding at the bone/implant interface was evaluated by tensile testing and undecalcified histological examination, at 8 and 16 weeks after implantation. The treated implants showed weak bonding to bone at 8 weeks, and exhibited significantly higher tensile failure loads compared with untreated tantalum implants at 16 weeks. The untreated implants showed almost no bonding, even at 16 weeks. Histological examination by Giemsa surface staining, contact microradiography (CMR), and scanning electron microscopy (SEM) revealed that treated tantalum implants bonded directly to bone tissue. In contrast, the untreated tantalum implants had a intervening fibrous tissue layer between the bone and the plate and did not bond to bone at 8 and 16 weeks. It is clear from these results that alkali and heat treatment induce the bone-bonding ability of tantalum. This new bioactive tantalum should be an effective material for weight-bearing and bone-bonding orthopedic devices.
