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Titania-based materials are attractive for hard tissue repair due to their bone-bonding ability induced by apatite formation in the body environment. Various surface treatments have therefore been developed to produce a hydrated titania layer on Ti and its alloys. Titania takes various valences, such as TiO (Ti2+) and Ti2O3 (Ti3+), as well as typical TiO2 (Ti4+); however, there is no comprehensive study of structural effects on the apatite-forming ability of these titanias. In this study, we investigated apatite formation on titania powders with various valences in simulated body fluid. Anatase- and rutile-type TiO2 formed apatite in simulated body fluid within 7 days, but TiO and Ti2O3 did not. In contrast, when the titania powders were treated with NaOH solution, the surface converted to tetravalent titania and all samples formed apatite. It is proposed that the surface electrical states of TiO and Ti2O3 are strongly affected by their bulk conductivity and that these behaved like pure Ti metal, which has poor apatite-forming ability. Apatite formation was favorable when the titania had a high absolute value and exhibited high fluctuations of zeta potential during initial stages in simulated body fluid, owing to adsorption of large amounts of Ca2+ and HPO42−.

Bioactivity modification helps polymethylmethacrylate (PMMA) bone cement to reinforce its interfacial adhesion to bone tissues through the chemical bonding of apatite. Since Si-OH groups combined w...

Ti–Zr alloys are expected to be novel biomaterials with low stress shielding owing to their lower Young’s moduli than pure Ti. The drawback of metallic biomaterials is that their bone-bonding abilities are relatively low. NaOH and heat treatments have been performed to provide Ti–50Zr with apatite-forming ability in the body environment, which is essential for bone bonding. However, the systematic compositional dependence of apatite formation has not been revealed. In the present study, NaOH treatment of Ti–Zr alloys with various compositions and bone-bonding abilities was assessed in vitro by apatite formation in simulated body fluid (SBF). The corrosion current density in NaOH aqueous solution and the amount of Na incorporated into the surface tended to decrease with increasing Zr content. The apatite-forming ability of the treated alloy significantly decreased when the Zr content was ≥60 atom%. This phenomenon is attributed to the (1) low OH content on the surface, (2) low Na incorporation into the treated alloy surface, which enhances apatite formation, and (3) low ability of P adsorption to the Ti–Zr alloy in SBF following Ca adsorption to trigger apatite nucleation. Although the adhesion of the titanate/zirconate layer formed on the surfaces to the substrates increased as Zr content increased, the adhesion between the apatite and the substrate was still low.

Nanocomposites of magnetite (Fe3O4) and reduced graphene oxide (rGO) generate heat under an alternating magnetic field and therefore have potential applications as thermoseeds for cancer hyperthermia treatment. However, the properties of such nanocomposites as biomaterials have not been sufficiently well characterized. In this study, the osteoconductivity of Fe3O4-rGO nanocomposites of various compositions was evaluated in vitro in terms of their apatite-forming ability in simulated body fluid (SBF). Furthermore, the heat generation of the nanocomposites was measured under an alternating magnetic field. The apatite-forming ability in SBF improved as the Fe3O4 content in the nanocomposite was increased. As the Fe3O4 content was increased, the nanocomposite not only rapidly raised the surrounding temperature to approximately 100 °C, but the specific absorption rate also increased. We assumed that the ionic interaction between the Fe3O4 and rGO was enhanced and that Brown relaxation was suppressed as the proportion of rGO in the nanocomposite was increased. Consequently, a high content of Fe3O4 in the nanocomposite was effective for improving both the osteoconductivity and heat generation characteristics for hyperthermia applications.

Open in a separate window Chemical modification with specific functional groups has been the conventional method to develop bone-bonding bioactive organic–inorganic hybrids. These materials are attractive as bone substitutes because they are flexible and have a Young’s modulus similar to natural bone. Immobilization of sulfonic acid groups (−SO3H) onto the polymer chain is expected to produce such hybrids because these groups induce apatite formation in a simulated body fluid (SBF) and enhance the activity of osteoblast-like cells. Sulfinic acid groups (−SO2H), which are derivatives of −SO3H, can also induce apatite nucleation. However, the structural effects of such sulfur-containing functional groups on apatite formation have not been elucidated. In the present study, apatite formation on Ca2+-modified copolymers containing −SO2H or −SO3H was investigated in a simulated body environment. The copolymer containing Ca2+ and −SO3H promoted Ca2+ release into the SBF and formed apatite faster (1 day) than the copolymer containing Ca2+ and −SO2H (14 days). In contrast, when they were not modified with Ca2+, the copolymer containing only −SO2H deposited the apatite faster (7 days) than that containing only −SO3H (>7 days) in the solution with Ca2+ concentration 1.5 times that of SBF. The former adsorbed larger amounts of Ca2+ than the latter. The measured stability constant of the complex indicated that the interaction of −SO2–···Ca2+ was more stable than that of −SO3–···Ca2+. It was found that both the release and adsorption of Ca2+ governed by the stability played an important role in induction of the apatite formation and that the apatite-forming ability of sulfur-containing functional groups drastically changed by the coexistence of Ca2+.

Organic–inorganic composites are novel bone substitutes that can ameliorate the mismatch of Young's moduli between natural bone and implanted ceramics. Phosphate groups contribute to the formation of apatite in a simulated body fluid (SBF) and the adhesion of osteoblast-like cells. Therefore, modification of a polymer with these functional groups is expected to enhance the ability of the organic–inorganic composite to bond with bone. Two phosphate groups have been used, phosphonic acid (–C–PO3H2) and phosphoric acid (–O–PO3H2). However, the effects of structural differences between these phosphate groups have not been clarified. In this study, the apatite formation of copolymers modified with Ca2+ and either –C–PO3H2 or –O–PO3H2 was examined. The mechanism of apatite formation is discussed based on analytical and computational approaches. The copolymers containing –O–PO3H2, but not those containing –C–PO3H2, formed apatite in the SBF, although both released similar amounts of Ca2+ into the SBF. Adsorption of HPO42− from –O–PO3H2 in the SBF following Ca2+ adsorption was confirmed by zeta-potential measurement and X-ray photoelectron spectroscopy. The measurement of the complex formation constant revealed that the –O–PO32−⋯Ca2+ complex was thermodynamically unstable enough to convert into CaHPO4, which was not the case with –C–PO32−⋯Ca2+. The formation of CaHPO4-based clusters was found to be a key factor for apatite nucleation. In conclusion, this study revealed that modification with –O–PO3H2 was more effective for enhancing apatite formation compared with –C–PO3H2.

Hafnium (Hf) has attracted considerable attention as a component of biomedical titanium (Ti) alloys with low Young's moduli and/or shape-memory functionalities, because its cytotoxicity is as low as that of Ti. The drawback of metals is that their bone-bonding ability is generally low. It is known that apatite formation in the body is a prerequisite for bone-bonding. Although several chemical treatments have been proposed for preparing Ti for bone-bonding, there have been no similar investigations for Hf. In the present study, NaOH- and heat-treatments were applied to pure Hf and Ti-Hf alloys and their bone-bonding ability was assessed in vitro with the use of simulated body fluid (SBF). After NaOH- and heat-treatments, anatase formed on alloys with low Hf content (20-40% (atom%) Hf); mixtures of sodium titanate and hafnium titanate formed on alloys with similar Ti and Hf content (60% Hf); and hafnium oxide formed on alloys with high Hf content (80% Hf and pure Hf). Precipitates of apatite were observed on all the metals in SBF, except for the alloy with 60% Hf. We speculated that the hafnium titanate formed on this alloy had a low apatite-forming ability owing to its high negative surface charge, which inhibited P adsorption. The apatite-forming abilities of the Ti-Hf alloys strongly depended on their Hf content. The present results indicate that Hf-based materials have good potential for bone-bonding. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2519-2523, 2018.

Polyetheretherketone (PEEK) has attracted much attention as an artificial intervertebral spacer for spinal reconstruction. Furthermore, PEEK plastic reinforced with carbon fiber has twice the bending strength of pure PEEK. However, the PEEK-based materials do not show ability for direct bone bonding, i.e., bioactivity. Although several trials have been conducted for enabling PEEK with bioactivity, few studies have reported on bioactive surface modification of carbon–PEEK composites. In the present study, we attempted the preparation of bioactive carbon-PEEK composites by chemical treatments with H 2 SO 4 and CaCl 2 . Bioactivity was evaluated by in vitro apatite formation in simulated body fluid (SBF). The apatite formation on the carbon–PEEK composite was compared with that of pure PEEK. Both pure PEEK and carbon-PEEK composite formed the apatite in SBF when they were treated with H 2 SO 4 and CaCl 2 ; the latter showed higher apatite-forming ability than the former. It is conjectured that many functional groups able to induce the apatite nucleation, such as sulfo and carboxyl groups, are incorporated into the dispersed carbon phase in the carbon–PEEK composites.

Natural bone consists of apatite and collagen fiber. Bioactive materials capable to bonding to bone tissue are clinically used as bone-repairing materials. Apatite-organic polymer composites exhibit bone-bonding abilities and mechanical properties similar to those of natural bone, and these materials can be prepared using biomimetic processes in simulated body fluid (SBF). Specific functional groups such as sulfonic and carboxylic acid groups are known to induce the heterogeneous nucleation of apatite in SBF. However, it remains unclear whether structurally related sulfinic acid groups can contribute to apatite formation in the same way, despite sodium sulfonate being used in biomedical applications as a radical polymerization promoter in adhesive dental resin. Herein, we report the preparation of a new hydrogel containing sulfinic acid groups from sodium 4-vinylbenzenesulfinate and 2-hydroxyethyl methacrylate using a radical polymerization reaction and the subsequent incorporation of Ca2+ ions into this material. We also investigated the apatite-forming behavior of these hydrogels in SBF. Hydrogels containing sulfinic acid groups showed higher apatite-forming ability than those without sulfinic acid groups. In addition, the apatite layer formed on the former showed tight adhesion to the hydrogel. This phenomenon was attributed to the heterogeneous nucleation of apatite, induced by the sulfinic acid groups. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1924-1929, 2017.

Polymethyl methacrylate (PMMA)-based bone cement is a popular biomaterial used for fixation of artificial joints. A next-generation bone cement having bone-bonding ability, i.e., bioactivity and antibacterial property is desired. We previously revealed that PMMA cement added with 2-(tert-butylamino)ethyl methacrylate, &gamma, methacryloxypropyltrimethoxysilane and calcium acetate showed in vitro bioactivity and antibacterial activity. This cement contains calcium acetate at 20% of the powder component. Lower content of the calcium acetate is preferable, because the release of a lot of calcium salt may degrade mechanical properties in the body environment. In the present study, we investigate the effects of calcium acetate content on the setting property and mechanical strength of the cement and apatite formation in simulated body fluid (SBF). The setting time increased and the compressive strength decreased with an increase in calcium acetate content. Although the compressive strength decreased after immersion in SBF for 7 d, all the cements still satisfied the requirements of ISO5833. Apatite was formed in SBF within 7 d on the samples where the calcium acetate content was 5% or more. Therefore, it was found that PMMA cement having antibacterial properties and bioactivity can be obtained even if the amount of the calcium acetate is reduced to 5%.

Cobalt-chromium (Co-Cr) alloys are used in clinical practice for the hard tissue reconstruction because of their favorable biocompatibility and mechanical properties. However, their applications have been limited because of their poor bioactivity, making them poor at bone-bonding. In this study, the bioactivity of a Co-Cr alloy was evaluated following the immobilization of cross-linked poly-γ-glutamic acid (γ-PGA) onto its surface via the formation of 11-aminoundecylphosphonic acid self-assembled monolayers (SAMs). Results of X-ray photoelectron spectroscopy revealed the presence of a new P2p peak, which confirms SAMs formation. Furthermore, the surface became highly hydrophobic following the immobilization with γ-PGA. Subsequent treatment with CaCl2 at 0.5 M or more and soaking in a simulated body fluid led to the formation of a low crystalline apatite. The present results show that chemical modification can be used to induce the formation of an apatite layer on the surface of a Co-Cr alloy in simulated body fluid.

Bioactive titania (TiO2) microparticles can be used as drug-releasing cement fillers for the chemotherapeutic treatment of metastatic bone tumors. Porous anatase-type TiO2 microspheres around 15 μm in diameter were obtained through a sol–gel process involving a water-in-oil emulsion with 30:70 SiO2/H2O weight ratio and subsequent NaOH solution treatment. The water phase consisted of methanol, titanium tetraisopropoxide, diethanolamine, SiO2 nanoparticles, and H2O, while the oil phase consisted of kerosene, Span 80, and Span 60. The resulting microspheres had a high specific surface area of 111.7 m2·g− 1. Apatite with a network-like surface structure formed on the surface of the microspheres within 8 days in simulated body fluid. The good apatite-forming ability of the microspheres is attributed to their porous structure and the negative zeta potential of TiO2. The release of rhodamine B, a model for a hydrophilic drug, was rapid for the first 6 h of soaking, but diffusion-controlled thereafter. The burst release in the first 6 h is problematic for clinical applications; nonetheless, the present results highlight the potential of porous TiO2 microspheres as drug-releasing cement fillers able to form apatite.

Bone cement from polymethylmethacrylate powder and methylmethacrylate liquid has been successfully demonstrated as artificial material to anchor joint replacements in bone. However, it lacks the capability to bond directly to bone, so long-term implantation leads to an increased risk of loosening. Bioactive materials show better performance in fixation to bone, and the chemical bonding depends on bone-like apatite formation. This is triggered by surface reactions with body fluid. For these reactions, superficial functional groups like silanol (Si–OH) are ideal sites to induce apatite nucleation and the release of Ca2+ ions accelerates the apatite growth. Therefore, incorporation of materials containing these key components may provide the cement with apatite-forming ability. In this study, phosphoric acid 2-hydroxyethyl methacrylate ester or bis[2-(methacryloyloxy)ethyl] phosphate supplying a phosphate group (PO4H2) was added into methylmethacrylate liquid, while calcium acetate as a source of Ca2+ ions was mixed into polymethylmethacrylate powder. The influences of the combinations on the setting time and compressive strength were also investigated. Apatite was formed on the cements modified with 30 mass% of phosphoric acid 2-hydroxyethyl methacrylate ester or bis[2-(methacryloyloxy)ethyl] phosphate. The induction period was shortened with increased amounts of Ca(CH3COO)2. The setting time could be controlled by the Ca(CH3COO)2/monomer mass ratio. Faster setting was achieved at a ratio close to the mixing ratio of the powder/liquid (2:1), and both increases and decreases in the amount of Ca(CH3COO)2 prolonged the setting time based on this ratio. The highest compressive strength was 88.8 ± 2.6 MPa, higher than the lowest limit of ISO 5833 but was lower than that of the simulated body fluid-soaked reference. The increase of additives caused the decline in compressive strength. In view of balancing apatite formation and clinical standard, bis[2-(methacryloyloxy)ethyl] phosphate is more suitable as an additive, and the optimal modification is a combination of 30 mass% of bis[2-(methacryloyloxy)ethyl] phosphate and 20 mass% of Ca(CH3COO)2.

Although titanium (Ti) is clinically used for hard tissue reconstruction, it has low bone-bonding ability, i.e. bioactivity. Materials able to deposit apatite on their surfaces within the body is considered to exhibit bioactivity. Effects of the metallographic structure and machining process of Ti on its apatite-forming ability remains unclear. In this study, Ti substrates subjected to various preheating and machining processes were then subjected to NaOH and heat treatments. The apatite-forming abilities of resulting Ti were examined in simulated body fluid (SBF). Preheating of the Ti decreased its reactivity with NaOH solution. When quenched or annealed Ti was subjected to NaOH and heat treatments, the induction period for apatite formation in SBF slightly increased. This was attributed to a decrease in sodium titanate and increase in rutile on the Ti surface after the treatments. Substrates subjected to wire-electrical-discharge machining did not form apatite. This was attributed to the inhibition of PO43- adsorption on their surfaces following Ca2+ adsorption, which is an essential process for apatite nucleation. Contamination of Ti surface by components of the brass wire used in the machining contributed to the inhibition. The bioactivity of surface-modified Ti was therefore significantly affected by its thermal treatment and machining process.

In this study, we investigated the surface structure, apatite formation in simulated body fluid (SBF), and visible-light photocatalytic activity of Ti metal subjected to chemical and thermal treatments. Ti metal samples treated with NaOH, a nitrogen-containing solution (0.1 M HNO 3 , 0.1–1.0 M (H 2 N) 2 C O, or 0.1–1.0 M NH 4 Cl), and heat showed apatite formation on their surfaces in SBF, whereas those treated with NaOH, 0.5 or 1.0 M HNO 3 , and heat did not. In the former case, apatite formation may be attributable to the fine network structure of anatase-type TiO 2 doped with a small amount of nitrogen on the surface of the Ti metal. The Ti metal treated with the latter treatment showed higher methylene blue decomposition than the untreated sample and the one treated with the former treatment. This preliminary result suggests that Ti metal treated with NaOH, 0.1 M HNO 3 , and heat can potentially show visible-light-induced antibacterial property as well as bone-bonding ability.

Apatite-polymer composites mimicking specific structure of natural bone are promised as bone substitutes with moderate flexibility able to be fabricated into desired shapes as well as bone-bonding bioactivity. In order to precipitate the apatite on polymer surfaces, aqueous processing using solution supersaturated to the apatite has been attracting as much attention. Polyglutamic acid (PGA) is a promised candidate of the polymer, since it has high apatite-forming ability owing to abundant carboxyl groups able to trigger the heterogeneous apatite nucleation. Although combination of PGA with different molecular weight is expected to provide design of organic-inorganic composites with moderate bioresorbability, precise relationship between the molecular weight of the PGA and its apatite-forming ability has been remained unclear. In the present study, PGA hydrogels with different molecular weight were prepared by covalent cross-linking using ethylenediamine. Difference in apatite formation in simulated body fluid (SBF) was interpreted in terms of their chemical structure. It was found that hydrogels prepared from PGA with higher molecular weight showed tendency to have higher apatite-forming ability. It was attributed to high content of the carboxyl group remaining on the hydrogel due to low degree of the cross-linking.

Chemically synthesized collagen with a triple helix structure similar to that of natural collagen is attractive as a safe biomaterial. Hybrids of chemically synthesized collagen and apatite are proposed for novel bone substitutes. However their apatite-forming ability in simulated body fluid is still quite low. We examined acceleration of apatite formation on collagen by immobilized poly-γ-glutamic acid (PGA), which has excellent apatite-forming ability. Apatite was formed within 3 days when collagen was treated with PGA solutions containing an appropriate amount of CaCl2. A mixture of apatite and calcite was formed at high CaCl2 concentration. The present results indicate the possibility of preparing hybrid materials, with tailored mechanical and biological properties, based on chemically synthesized collagen.

The glass ionomer cement as one of the dental cements has been subjected to be widespread application in restoring tooth structure. Most of glass ionomer cements employ the poly(acrylic acid) (PAA) as the liquid phase, but the presence of PAA inhibits the apatite formation on the surface in the body environment, which is an essential requirement for exhibiting bone-bonding ability (bioactivity). In this study, poly(γ-glutamic acid) (γ-PGA), a kind of biopolymer, was utilized for cement preparation. The effort of preparation parameters including the glass powders/liquid ratio (P/L) and the concentration ofγ-PGA on diametral tensile strength were investigated. A maximum diametral tensile strength value of11.88±1.43MPa was obtained when the cement sample was prepared by P/L ratio of 1 : 1 and theγ-PGA concentration of 30% after aging for 3 days. The TF-XRD patterns, SEM images, and EDX spectra suggested that the cement induced a precipitation of calcite on the surface after 7 days of immersion in stimulated body fluid (SBF), although the apatite formation was not observed. The present results suggest that the cement has potential to show bioactivityin vivo, because calcite is also reported to be bioactive.

Porous and non-porous titania microspheres with the anatase or rutile phase were successively prepared by the sol–gel process followed by heat treatment at various temperatures. The pore size of the prepared microspheres was effectively controlled by incorporating silica nanoparticles of different diameters. The apatite-forming ability of the microspheres was investigated in a simulated body fluid, with ion concentrations nearly equal to those of human blood plasma. Results indicated that the titania microspheres with either anatase or rutile structure induced the formation of calcium phosphate compounds (CaPs) on the microsphere surface. The deposition of CaPs was more pronounced on the TiO2 microspheres calcined at 600°C (anatase structure) and 800°C (rutile structure), compared to that calcined at 500°C (anatase structure). Additionally, anatase microspheres with smooth surface and low specific surface area favored the formation of CaPs, compared to porous microspheres. This indicates that nanoscale pores do not essentially favor apatite formation.

Several varieties of ceramics, such as Bioglass-type glasses, sintered hydroxyapatite and glass-ceramic A–W, exhibit specific biological affinity, i.e., direct bonding to surrounding bone, when implanted in bony defects. These bone-bonding ceramics are called bioactive ceramics and are utilized as important bone substitutes in the medical field. However, there is a limitation to their clinical applications because of their inappropriate mechanical properties. Natural bone takes a kind of organic–inorganic composite, where apatite nanocrystals are precipitated on collagen fibers. Therefore, problems with the bioactive ceramics can be solved by material design based on the composites. In this paper, current research topics on the development of bioactive organic–inorganic composites inspired by actual bone microstructure have been reviewed in correlation with preparation methods and various properties. Several kinds of inorganic components have been found to exhibit bioactivity in the body environment. Combination of the inorganic components with various organic polymers enables the development of bioactive organic–inorganic composites. In addition, novel biomedical applications of the composites to drug delivery systems, scaffolds for tissue regeneration and injectable biomaterials are available by combining drugs or biological molecules with appropriate control of its microstructure.

Sodium hydroxide (NaOH)-, heat- and autoclave-treated Ti metal did not form apatite in simulated body fluid (SBF) within 604.8ks, although some Na remained on the Ti metal surface after the autoclave treatment. When hot water treatment was applied between NaOH and heat treatments, the Ti metal formed apatite within 604.8ks in SBF. While anatase TiO2 was partially precipitated by the NaOH and heat treatments, it disappeared after subsequent autoclave treatment. By adding hot water treatment between the NaOH and heat treatments, a considerable amount of anatase TiO2 was formed, which remained after the autoclave treatment; the zeta potential of Ti metal was almost zero in SBF. These results indicate that with intermediate hot water treatment, Ti metal can form apatite in SBF even after autoclave treatment. Anatase TiO2, rather than the amount of Na or the zeta potential in SBF, might play an important role in apatite formation.

Phosphate groups on materials surfaces are known to contribute to apatite formation upon exposure of the materials in simulated body fluid and improved affinity of the materials for osteoblast-like cells. Typically, polymers containing phosphate groups are organic matrices consisting of apatite-polymer composites prepared by biomimetic process using simulated body fluid. Ca(2+) incorporation into the polymer accelerates apatite formation in simulated body fluid owing because of increase in the supersaturation degree, with respect to apatite in simulated body fluid, owing to Ca(2+) release from the polymer. However, the effects of phosphate content on the Ca(2+) release and apatite-forming abilities of copolymers in simulated body fluid are rather elusive. In this study, a phosphate-containing copolymer prepared from vinylphosphonic acid, 2-hydroxyethyl methacrylate, and triethylene glycol dimethacrylate was examined. The release of Ca(2+) in Tris-NaCl buffer and simulated body fluid increased as the additive amount of vinylphosphonic acid increased. However, apatite formation was suppressed as the phosphate groups content increased despite the enhanced release of Ca(2+) from the polymer. This phenomenon was reflected by changes in the surface zeta potential. Thus, it was concluded that the apatite-forming ability of vinylphosphonic acid-2-hydroxyethyl methacrylate-triethylene glycol dimethacrylate copolymer treated with CaCl2 solution was governed by surface state rather than Ca(2+) release in simulated body fluid.

Sodium hydroxide (NaOH)-, heat- and autoclave-treated Ti metal did not form apatite in simulated body fluid (SBF) within 7 days although certain amounts of sodium (Na) still remained on the Ti metal surface even after the autoclave treatment. When hot water treatment was applied between NaOH and heat treatment, the Ti metal formed apatite within 7 days in SBF. Anatase-type TiO2 was partially precipitated by the NaOH and heat treatment but it was disappeared by the subsequent autoclave treatment. When the hot water treatment was applied between the NaOH and heat treatment, considerable amount of anatase-type TiO2 was formed and it still remained even after the autoclave treatment. The zeta potential of the Ti metal with the hot water treatment was almost zero in SBF. These results indicate that Ti metal can show apatite-forming ability in SBF even after autoclave treatment, when hot water treatment is applied between the NaOH and heat treatment, and that anatase-type TiO2 might play an important role in the apatite formation rather than the amount of Na and/or the zeta potential.

Chemically synthesized collagen with triple helix structure similar to natural collagen has been developed as a safe biomaterial. If the chemically synthesized collagen is deposited with apatite, they are expected for novel bone substitutes having bioactivity and bioresorbability. Although apatite formation on the chemically synthesized collagen has been examined, highly supersaturated condition such as 1.5SBF with ion concentration 1.5 times those of simulated body fluid (SBF) is needed to achieve apatite formation. In the present study, we intended acceleration on the apatite formation on the chemically synthesized collagen by immobilization with polyglutamic acid (PGA). PGA is known as biodegradable and biocompatible polypeptide having excellent apatite-forming ability. We examined effects of the immobilization procedure on mineralization behavior in SBF. At first, PGA was immobilized on porous sponges of chemically synthesized collagen in aqueous solutions containing PGA and CaCl2. As a result, not only apatite but also calcite-type CaCO3 was deposited on the specimens in SBF. The calcite formation was occurred during the treatment with PGA solution. pH of the solution was adjusted to 7 by NaOH solution in order to avoid dissolution of the collagen. During this procedure, Ca (OH)2 would be precipitated by locally increase in pH of the solution and converted into the calcite. When the PGA solution treatment was shortened so as to prevent the calcite formation, single phase of the apatite was formed in SBF. The present results indicate that crystalline phase deposited on the chemically synthesized collagen can be controlled by fabrication procedure, and provide fundamental design of composites containing apatite and chemically synthesized collagen useful for bone regeneration.

Osteoconductive materials with self-setting ability have received much attention because their properties allow developing injectable materials for bone defects. Thermosensitive hydrogel with ability of bone-like apatite formation in a body environment is a candidate of injectable bone fillers with osteoconductivity because the apatite formation on materials is an essential to show osteoconduction. The present study focused on the development of a thermosensitive hydrogel through modifications of the sulphonic groups of the polysaccharide, κ-carrageenan, with potassium chloride (KCl) and calcium chloride (CaCl 2 ). We found that the gelation temperature of κ-carrageenan solutions increased with increasing amounts of K + ions. Apatite formation was observed on the gel after exposure to simulated body fluid for 0.5 day when the gel was prepared with a molar ratio of Ca 2+ /sulfonic groups = 1.5. These results indicate that a thermosensitive κ-carrageenan hydrogel with apatite-forming ability was obtained through the incorporation of K + and Ca 2+ ions into the solution.

Organic–inorganic hybrids with apatite-forming abilities in physiological environments offer possibilities for building flexible bone-bonding bioactive materials; several functional groups are known to induce apatite nucleation. Here, bioactive organic–inorganic hybrids from κ-carrageenan and λ-carrageenan containing sulfonic groups were prepared. Carrageenan hydrogels were made by cross-linking with CaCl2. The apatite-forming abilities of each kind of carrageenan hydrogel were examined using simulated body fluid (SBF); λ-carrageenan was found to be superior to κ-carrageenan for this purpose. The former swelled significantly in aqueous conditions, releasing a large amount of Ca2+ ions into the SBF, contributing to rapid apatite formation.

Polymethylmethacrylate (PMMA)-based bone cement is widely used for the fixation of artificial joints. However, it is not considered a bioactive material because it lacks the ability to induce a direct bond with bone. In order to improve the long-term stability of cemented fixations, the development of bioactive bone cements is desirable. An essential requirement of a bioactive material includes the induction of bone-like apatite on its surface within the in vivo environment. Previously, we prepared bioactive PMMA-based bone cements by a modification with water-soluble calcium salts and alkoxysilane. Because spatial design may enhance apatite formation on bioactive material surfaces in vivo, we aimed to evaluate the effect of spatial design on apatite formation on modified PMMA-based bone cements in simulated body fluid (SBF). We found that an appropriate spatial design shortened the induction period for the apatite deposition on the modified bone cements. It is expected that osteoconduction would be enhanced in spontaneously created gap between the cement and the host bone leading to tight integration.

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.

Objective 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. Study design Titanium implants were alkaline treated, heat activated, and soaked in stimulated body fluid with or without BMP-2/heparin to coat the apatite around them. Treated implant bars were then implanted in rat tibiae. After 3 weeks, nondecalcified sections were prepared and the new bone formation around the implants was examined. Results A greater amount of bone formed on the apatite-coated implants containing BMP-2/heparin than on apatite-coated implants containing BMP, with ≥3 μg/mL heparin. Apatite-coated titanium implants with BMP-2/heparin had significantly enhanced new endosteal bone formation, with increases vertically (134%) and horizontally (124%). Conclusions Bone formation was stimulated around the apatite-covered titanium coated with BMP-2/heparin, which may be useful in improving implant therapy.

Natural bone has features such as high fracture toughness and bone-bonding bioactivity, and is organic–inorganic hybrid composed of collagen and apatite crystals. Therefore, apatite-polymer hybrids designed to mimic the structure of bone represent candidates for high-performance bone substitutes. In this study, we prepared pectin hydrogels through covalent cross-linking using divinylsulfone (DVS) and investigated their apatite-forming abilities of the gels in simulated body fluid (SBF) and mechanical properties by tensile test. The obtained results were interpreted in terms of surface charge of the gels and chemical reaction with SBF. The apple- and citrus-derived gels formed the apatite on their surfaces in SBF within 3 days. These gels showed tensile strength around 30 MPa.

So-called bioactive ceramics exhibit specific biological affinity, i.e. direct bonding to surrounding bone, when implanted in bony defects. However, there is limitation on clinical applications, because of their inappropriate mechanical properties such as low fracture toughness and high elastic modulus. Novel bioactive materials exhibiting high flexibility have been desired. The essential prerequisite for artificial materials to exhibit bioactivity is deposition of bone-like apatite on their surfaces in body environment. This apatite deposition is governed not only by the dissolution of the materials but also by heterogeneous nucleation on the materials surface, followed by crystal growth by consuming calcium and phosphate ions from surrounding body fluid. These findings bring us an idea that bioactive organic-inorganic hybrids with high flexibility can be developed by control in direction and amounts of transformed chemical species. So, the control in chemicovectors on bioactive materials provides attractive design of bone-bonding materials with various functionalities. In this paper, we review development of organic-inorganic hybrids from hydroxyethylmethacrylate (HEMA), starch and collagen-like polypeptide, on the view points of chemicovector.

Apatite formation in the living body is an essential requirement for artificial materials to exhibit bone-bonding bioactivity. It has been recently revealed that sulfonic groups trigger apatite nucleation in a body environment. Organic-inorganic hybrids consisting of organic polymers and the sulfonic groups are therefore expected to be useful for preparation of novel bone-repairing materials exhibiting flexibility as well as bioactivity. In the present study, organic-inorganic hybrids were prepared from hydroxyethylmethacrylate (HEMA) in the presence of vinylsulfonic acid sodium salt (VSAS) and calcium chloride (CaCl(2)). The bioactivities of the hybrids were assessed in vitro by examining the apatite formation in simulated body fluid (SBF, Kokubo solution). The hybrids deposited on the apatite after soaking in SBF within 7 days. Tensile strength measurements showed a tendency to increase with increases in VSAS and CaCl(2) content. It was assumed that this phenomenon was attributed to the formation of cross-linking in the hybrids.

Hydroxyapatite (HA) films were deposited onto titanium (Ti) metal substrates by an electrodeposition method under a short-pulse current. Metastable calcium phosphate solution was used as the electrolyte. The ion concentration of the solution was 1.5 times that of human body fluid, but the solution did not contain magnesium ions at 36.5°C. We used an average current density of 0.01 A/cm2 and current-on time (TON) equal to current-off time (TOFF) of 10 ms, 100 ms, 1 s, and 15 s. The adhesive strength between HA and Ti substrates were relatively high at TON = TOFF = 10 ms. It is considered that small calcium phosphate crystals with low crystallinity were deposited on the Ti surface without reacting with other calcium phosphate crystals, H2O, and HCO3– in the surrounding environment. This resulted in relaxation of the lattice mismatch and enhancement of the adhesive strength between the HA crystals and Ti substrates.

Bioactive ceramics have high biological affinity that enables direct bone-bonding. However they do not have mechanical performances enough to repair bone tissue under loaded conditions. It has been revealed that most materials exhibiting bioactivity form bone-like apatite in body environment. We investigated apatite-forming ability of tantalum- and niobium-based oxide gels in simulated body environment in order to fundamentally clarify chemical structure effective for achieving bioactivity. We found that Ta-OH and Nb-OH groups on the surfaces of the oxide gels have a potential to form the apatite. On the basis of these findings, we have successfully provided tough tantalum metal with bioactivity by simple NaOH and heat treatments that form a lot of Ta-OH groups on their surfaces. We also synthesized bioactive organic-inorganic hybrids with flexibility by organic modification of inorganic chemical species with apatite-forming ability. A sequence of material design described above would produce bioactive materials with various mechanical properties.

Apatite-polymer hybrids are expected as novel bone substitutes exhibiting bone-bonding ability, i.e. bioactivity, and mechanical performances analogous to those of natural bone. To fabricate such hybrids, biomimetic process has been paid much attention where bone-like apatite is deposited on organic polymers that have specific functional groups in simulated body fluid (SBF) or more concentrated solutions. Previous studies showed that carboxyl groups (-COOH) have a catalytic effect for heterogeneous apatite nucleation in SBF. In this study, we chose pectin as an organic polymer. Pectin is a natural polysaccharide containing carboxyl groups. Hydrogels were prepared from various pectins including pectic acid, apple-derived pectin and citrus-derived pectin by treatment with CaCl2 solution. Ability of apatite formation in SBF and mechanical properties of the gels were examined. The apatite-forming ability increased in the order (pectic acid)

Materials with bioactivity, i.e. bone-bonding ability, form a bone-like apatite layer on their surfaces in the body and bond to living bone through this bone-like apatite layer. Bone-like apatite is carbonated hydroxyapatite with small crystallites and low crystallinity. The coating of the bone-like apatite layer on the substrates is expected to be a useful technique to induce bioactivity on the substrates. The bone-like apatite layer can be formed on the surface of substrates in a solution mimicking body fluid when some functional groups are introduced to the substrates. This process is called a biomimetic process. Coating of bone-like apatite layers through this biomimetic process has received much attention in the fabrication of novel composites with bioactivity. An overview of the coating of bone-like apatite is described.

So-called bioactive ceramics are used for bone-repairing owing to attractive features such as direct bone-bonding in living body. However, there is limitation on clinical applications due to their inappropriate mechanical properties performances such as higher brittleness and lower fracture toughness than natural bone. To overcome this problem, hybrid materials have been developed by modification of calcium silicate, that is basic component of bioactive ceramics, with organic polymer. It is known that bioactive ceramics bond to bone through bone-like apatite layer which is formed on their surfaces by chemical reaction with body fluid. We attempted preparation of bioactive organic-inorganic hybrids from Glucomannan that is a kind of complex polysaccharide, and calcium silicate. Hybrids were prepared from glucomannan and tetraethoxysilane (TEOS). They were treated with 1M (=mol·m-3) CaCl2 aqueous solution for 24 hours. Then ability of apatite formation on the hybrids was examined in vitro using simulated body fluid (SBF, Kokubo solution). Surface structure of the specimens was examined by thin-film X-ray diffraction (TF-XRD), scanning electron microscopic (SEM) observation. The hybrids with TEOS:Glucomannan= 1:1 to 4:1 in mass ratio formed the apatite in SBF within 3 or 7 d, when they were previously treated with CaCl2 solution.

Natural bone is a kind of organic-inorganic hybrid composed of collagen and apatite crystals with a structure that provides specific mechanical properties such as high fracture toughness and flexibility. Materials exhibiting both high flexibility and bioactivity similar to natural bone are required for novel bone-repairing materials in medical fields. We expect that we can design such materials by mimicking the bone structure. Biomimetic process has been paid much attention where bone-like apatite is deposited on organic polymers in simulated body fluid (SBF). In this study, we investigated influence of cross-linking agents on apatite-forming ability of pectin gels. Pectin is a polysaccharide abundant in carboxyl group. Pectin gels were prepared by cross-linking of pectin aqueous solutions with calcium ions or divinylsulfone (DVS). Apatite-forming ability of the gels was examined in SBF. The citrus-derived pectin showed tendency to form the largest amount of the apatite independent on a kind of cross-linking agents in SBF.

The so-called bioactive ceramics have been attractive because they spontaneously bond to living bone. Organic—inorganic hybrids consisting of organic polymers and the essential constituents of the bioactive ceramics, i.e., silanol (Si—OH) group and calcium ions (Ca2+), are useful as novel bone substitutes, owing to bioactivity and high flexibility. In the present study, organic—inorganic hybrids are synthesized from chitin by modification with glycidoxypropyltrimethoxysilane (GPS) and calcium chloride (CaCl2). Their apatite-forming ability is examined in a simulated body fluid (SBF). The prepared hybrids form apatite on their surfaces in SBF within 7 days.

Bioactive ceramics have attractive feature for bone repair such as direct bone-bonding in the body. However their clinical application is limited to low loaded portions due to their inappropriate mechanical performances such as higher brittleness and lower flexibility than natural bone. The essential condition for artificial materials to show bioactivity is formation of bone-like apatite on their surfaces in body environment. This apatite formation is triggered by silanol (Si–OH) group on the material surfaces and release of Ca2+. These findings bring us an idea that novel bioactive materials with high flexibility can be designed by organic modification of calcium silicate. We synthesized organic–inorganic hybrids from organic polymers including 2-hydroxyethylmethacrylate (HEMA), starch and alginate by modification with alkoxysilane and calcium chloride. The hybrids formed apatite on their surfaces in simulated body fluid (SBF, Kokubo solution). Such a modification was also effective for providing conventional polymethylmethacrylate (PMMA)-based bone cement with bioactivity., IX Conference and Exhibition of the European Ceramic Society: June 19-23, 2005, Portorož, Slovenia

Development of the organic-inorganic hybrids composed of apatite crystals and organic polymer is expected to be an attractive material that has mechanical properties similar to natural bone as well as bone-bonding ability, i.e. bioactivity. It is reported that the carboxyl groups (-COOH) on the surfaces of the organic substrates act as a catalyst for induction of heterogeneous nucleation of apatite. The present authors previously showed that the apatite was successfully deposited on the polyglutamic acid gels containing abundant carboxyl groups through the biomimetic process, when they were priorly treated with calcium chloride solution. In this study, we fabricated the polyglutamic acid gels with different degree of cross-linking. Effect of the cross-linking on their ability of the apatite formation was examined in simulated body fluid (SBF). It was suggested that the apatite deposition on the polyglutamic acid gels is governed not only by the amount of –COOH that induces the heterogeneous nucleation of the apatite, but also by swelling property that controls local increase in degree of supersaturation with respect to the apatite.

Apatite-polymer hybrids are expected as novel bone substitutes exhibiting bone-bonding ability and mechanical performances analogous to those of natural bone. In this study, we attempted preparation of organic-inorganic hybrids from different pectins such as pectic acid, apple-derived pectin and citrus-derived pectin through apatite deposition in simulated body fluid (SBF). Pectin gels were prepared by CaCl2 treatment of aqueous solutions of pectin. Apatite-forming ability of the gels was examined in SBF. The citrus-derived pectin showed tendency to form the largest amount of the apatite in SBF.

So-called bioactive ceramics bond to living bone through the apatite layer formed on their surfaces in the body. The apatite deposition is triggered by dissolution of calcium ion (Ca2+) and by silanol (Si-OH) group formed on the surfaces of the ceramics. It is expected that organic modification of these components would produce bioactive materials with high flexibility. In this study, we examined bioactivity and mechanical properties of the organic-inorganic hybrids from starch by modification with silanol group and calcium ion. Effect of cross-linking agent was also investigated. The obtained hybrids showed bioactivity and mechanical properties analogous to those of human cancellous bone by appropriate control in their compositions. Addition of cross-linking agent to improve mechanical strength of the hybrids did not decrease their bioactivity.

Modification of organic polymer with silanol groups in combination with calcium salts enables the polymer to show bioactivity, that is, the polymer forms apatite on its surface after exposure to body environment. However, how modification with silanol groups influences ability of apatite formation on the polymer substrate and adhesive strength between polymer and apatite is not yet known. In the present study, polyamide containing carboxyl groups was modified with different amounts of silanol groups, and its apatite-forming ability in 1.5SBF, which contained ion concentrations 1.5 times those of simulated body fluid (SBF), was examined. The rate of apatite formation increased with increasing content of silanol groups in the polyamide films. This may be attributed to enhancement of dipole interactions. A tendency for the adhesive strength of the apatite layer on the polyamide film to be decreased with increasing content of silanol groups was observed. This may be attributed to swelling in 1.5SBF and having a high degree of shrinkage after drying. These findings clearly show that modification of organic polymers with the functional groups induces apatite deposition, and also determines the adhesive strength of the apatite layer to the organic substrates.

So-called bioactive ceramics can directly bond to living bone through the apatite layer formed on their surfaces in the body. However, hard and brittle character of ceramics limits their clinical applications to low loaded portions. The apatite deposition on the bioactive ceramics is known to be triggered by a catalytic effect of silanol (Si-OH) groups formed on their surfaces and by release of calcium ions (Ca 2þ ) that increases degree of supersaturation of the surrounding fluid with respect to the apatite. It is expected that organic modification of these components would produce bioactive materials with mechanical properties analogous to natural bone. We previously reported that bioactive organic-inorganic hybrids can be prepared from starch by modification with glycidoxypropyltrimethoxysilane (GPS) that provides with Si-OH groups and calcium chloride that releases calcium ions. In this study, we examined effect of synthetic conditions of the hybrids on their bioactivity and mechanical properties. We prepared several hybrids with different content of divinylsulfone as a cross-linking agent. Their bioactivity was examined in simulated body fluid (SBF, Kokubo solution) with inorganic ion concentrations nearly equal to those of human extracellular fluid. Materials that form the apatite on their surfaces in SBF are known to have a potential to show the bone-bonding. It was found that the added cross-linking agent did not decrease apatite-forming ability of the hybrids in SBF. Mechanical properties of the hybrids were further evaluated by a tensile test. Tensile strength and Young’s modulus increased with increasing content of divinylsulfone. [doi:10.2320/matertrans.48.317]

Natural bone is a kind of organic–inorganic hybrid that is composed of collagen and apatite nanocrystals. Organic polymer–apatite hybrid is therefore expected as novel bone substitutes exhibiting both bone-bonding ability and mechanical performance analogous to natural bone. Biomimetic process has been paid much attention on fabrication of such hybrids, where bone-like apatite is deposited on material surfaces in a simulated body fluid (SBF, Kokubo solution) with ion concentrations nearly equal to those of human extracellular fluid at ambient conditions. Hydroxyl groups on several kinds of metal oxide gels effectively trigger heterogeneous nucleation of the apatite in body environment. This is significantly enhanced by release of calcium ions from the materials. In this study, we synthesized organic–inorganic hybrids from poly(vinyl alcohol) (PVA) by modification with silica as well as calcium nitrate. PVA has attractive features for bone substitutes such as high hydrophilicity and high flexibility. Ability of the apatite formation was examined in SBF. Apatite deposition was observed on the surfaces of the hybrids in SBF. The PVA–apatite hybrids obtained are expected as novel bone-repairing materials.

Some ceramics show bone-bonding ability, i.e. bioactivity. Apatite formation on ceramics is an essential condition to bring about direct bonding to living bone when implanted into bony defects. A controlled surface reaction of the ceramic is an important factor governing the bioactivity and biodegradation of the implanted ceramic. Among bioactive ceramics, glass-ceramic A-W containing apatite and wollastonite shows high bioactivity, as well as high mechanical strength. In this study, glass-ceramics containing zinc oxide were prepared by modification of the composition of the glass-ceramic A-W. Zinc oxide was selected to control the reactivity of the glass-ceramics since zinc is a trace element that shows stimulatory effects on bone formation. Glass-ceramics were prepared by heat treatment of glasses with the general composition: xZnOx(57.0-x)CaOx35.4SiO(2)x7.2P(2)O(5)x0.4CaF(2) (where x=0-14.2mol.%). Addition of ZnO increased the chemical durability of the glass-ceramics, resulting in a decrease in the rate of apatite formation in a simulated body fluid. On the other hand, the release of zinc from the glass-ceramics increased with increasing ZnO content. Addition of ZnO may provide bioactive CaO-SiO(2)-P(2)O(5)-CaF(2) glass-ceramics with the capacity for appropriate biodegradation, as well as enhancement of bone formation.

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.