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Background/aim Curcumin is a natural compound of turmeric, which inhibits prostate cancer cell proliferation. This study examined whether treatment of LNCaP prostate cancer cells with the combination of curcumin and dutasteride, a 5-alpha reductase inhibitor, affect proliferation and the amount of testosterone and dihydrotestosterone. Materials and methods LNCaP Cells were incubated with curcumin or the combination of curcumin and dutasteride and cell proliferation was measured at 72 h. LC-MS/MS was used to determine testosterone and dihydrotestosterone concentrations in prostate cancer cells. Results Curcumin combined with dutasteride suppressed proliferation and affected apoptosis of LNCaP cells. The combination of curcumin and dutasteride also reduced the amount of testosterone and dihydrotestosterone in LNCaP cells. The secretion of prostate-specific antigen was inhibited by the combination treatment in a dose-dependent manner. Conclusion Treatment with the combination of curcumin and dutasteride may interfere with the intra-tumoral androgen activity.

Sub-µm CaCO3 (calcite; CC) particles were converted to calcium monohydrogenphosphate dihydrate (DCPD) and hydroxyapatite (HAp) via soaking treatments in K2HPO4 solutions with varied pH (3–12) and concentrations (0.1–1.5 M) at 37°C for up to 10 days. DCPD was derived from the solutions with pH ≤ 6; while hollow HAp was yielded when pH ≥ 7 in assemblies of petal-like crystallites. Results of magic angle spinning (MAS) and cross-polarization magic angle spinning (CP-MAS) NMR studies have shown that the HAp lattice has only PO4 2− but no HPO4 2− at B (phosphate) sites. Trace amounts of CO3 2− have occupied both A (OH) and B (PO4) sites, and H2O is adsorbed on surface crystallites. The primary crystallite size of HAp derived from Scherrer equation increases quickly in a 12 h period and becomes gradually stable afterward. Samples of particles soaked within 3 h in a temperature range of 20–80°C were analyzed by X-ray diffraction. It is shown that the rate constant of 1 M solution is about an order of magnitude greater than that of 0.1 M solution and the apparent activation energy is 33 kJ/mol. In this work, the conversion of CC to HAp can be quantitatively controlled to solve the problem of slow degradation of HAp.

In situ anatase thin film with high percentage exposure of {001} facet was fabricated on titanium substrate via one-step hydrothermal method at low temperature from the precursor solution of (NH4)2TiF6 and HF. Nano-inverted bipyramid arrays densely covered the whole surface on as-treated Ti substrate. The structural analysis clearly indicated that as-deposited thin film only consisted of anatase TiO2 single crystal with preferred oriented {001} facets. According to the XRD patterns of as-treated anatase thin film, the integral intensity ratio of (004) to (101) peaks was as high as 7.5 which was remarkably higher than the standard value 0.18. Based on the experimental results, the growth pattern and bonding strength of nano-structural array with high percentage exposure of anatase {001} facet on Ti substrate were discussed. The biocompatibility results demonstrated that MC3T3-E1 cells grown on the as-treated Ti sheet exhibited positive effect on the cell proliferation and significantly high gene expression of ALP, COL-1, BMP-2, OPN and RUNX2 due to its specific property of the surface. Hence, the in situ anatase thin film with high percentage exposure of {001} facet was expected to achieve satisfactory primary stability for osseointegration. In situ fabrication of anatase TiO2 nano-inverted bipyramid arrays with high percentage exposure of {001} facet

Conversion of calcium carbonate (calcite; CC) to hydroxyapatite (HAp) was examined when the CC particles of sub μm size were soaked at 37 °C for up to 10 d in 0.15 M K2HPO4 (20 ml), whose pH was set to 3–12. Here, the solution contained amino acids, such as glutamine (Glu), arginine (Arg), and glycine (Gly), and their content varied from 0–1.0 g per ml of solution. From the X-ray diffraction (XRD) intensity of the 104 and 211 diffractions of calcite and apatite, respectively, it was seen that the presence of the amino acids promoted the conversion. This was supported by the thermogravimetry (TG) results. The highest promotion was observed at 0.5 g addition of amino acids to the phosphate solution, while Glu showed the highest promotion among the amino acids and Gly the lowest. A scanning electron microscopy study indicated that petal-like HAp nano-crystallites covered the entire surface of the CC particles when they were soaked in the phosphate solution with 0.1 g or more of amino acid for 10 d. The XRD intensity ratio 104(CC)/211(HAp) indicated greater CC to HAp conversion in the solutions at pH 3 and 6 than in the more alkaline solutions. This was attributed to the dissolution of CC in the acidic solutions, which was confirmed by bubbling in these solutions.

Current apheresis or blood purification practices depend primarily on polymer systems that enable filtering and adsorbing pathogenic substances in blood: the latter consist of base polymer-based carriers and active ligands. However, some ceramic materials, such as silica, titania, and hydroxyapatite, are known to be blood compatible. The research on their use for apheresis is very small in comparison to the polymer systems, but the ceramic-based materials have been steadily discussed until now. This article aims to provide some feasible ideas and strategies together with their microstructures for further apheresis applications. After blood clotting pathways and apheresis practice, several blood-compatible materials in the form of particles, coatings (layers), and macrospheres are introduced. In addition, the materials for stent applications are also mentioned because the highest blood compatibility is demanded. Examples of bilirubin, b2-microglobulin (B2M), bovine serum albumin (BSA), and lysozyme (LYZ) adsorption on titania gel particles, Zn-substituted hydroxyapatite, and so-gel derived silica macrospheres are presented.

Microporous spheres in a hybrid system consisting of chitosan and &gamma, glycidoxypropyltrimethoxysilane (GPTMS) have advantages in a range of applications, e.g., as vehicles for cell transplantation and soft tissue defect filling materials, because of their excellent cytocompatibility with various cells. In this study, microporous chitosan-GPTMS spheres were prepared by dropping chitosan-GPTMS precursor sols, with or without a cerium chloride, into liquid nitrogen using a syringe pump. The droplets were then freeze dried to give the pores of size 10 to 50 &mu, m. The cell culture tests showed that L929 fibroblast-like cells migrated into the micropores larger than 50 &mu, m in diameter, whereas MG63 osteoblast-like cells proliferated well and covered the granule surfaces. The spheres with cerium chloride showed antibacterial properties against both gram-negative and gram-positive bacteria.

International audience; We demonstrate that NMR/DNP (Dynamic Nuclear Polarization) allows an unprecedented description of carbonate substituted hydroxyapatite (CHAp). Key structural questions related to order/disorder and clustering of carbonates are tackled by using distance sensitive DNP experiments using 13 C-13 C recoupling. Such experiments are easily implemented due to unprecedented DNP gain (orders of magnitude). DNP is efficiently mediated by quasi one-dimensional spin diffusion through the hy-droxyl columns present in the CHAp structure (thought as "highways" for spin diffusion). For spherical nanoparti-cles and ∅ < 100 nm, it is numerically shown that spin diffusion allows their study as a whole. Most importantly, we demonstrate also that the DNP study at 100 K leads to data which are comparable to data obtained at room temperature (in terms of spin dynamics and lineshape resolution). Finally, all 2D DNP experiments can be interpreted in terms of domains exhibiting well identified types of substitution: local order and carbonate clustering are clearly favored.

Novel silica hollow flowers (1–5 μm) were synthesized using globular apatite flowers as sacrificed template via a sol–gel route and then employed as biocompatible carrier of bone morphogenetic protein-2 (BMP-2) to stimulate osteoblast differentiation. Apatite was bio-mimetically synthesized from a well-known Kokubo’s simulated body fluid (SBF), then coated with silica in a Stober-type silica sol–gel system, and finally dissolved in an acetic solution to yield silica hollow flowers. Analyses of SEM and TEM images show that the resultant silica flowers had a porous and hollow structure due to removal of apatite template by acetic treatment and their shell was constructed by numerous silica nanosheets (∼10 nm in silica shell). A larger specific surface of 890 m 2 /g was obtained for silica hollow flowers compared to silica-coated apatite due to the presence of porous and hollow structure. Silica hollow flowers had no significant toxicity after incubation with osteoblast MC3T3-E1 cells, indicating a good biocompatibility. They favored adsorption and supported a sustained release behavior of BMP-2. The released BMP-2 was biological active and enhanced osteoblast differentiation with higher ALP activity and larger amount of osteocalcin. The present silica hollow flowers are thus applicable to delivery system in tissue generation.

Rough nanostructured anatase TiO 2 surfaces containing many pores were prepared by the hydrothermal-based method. Surface modification with self-assembled monolayers (SAMs) of octadecylphosphonic acid (ODP) resulted in the superhydrophobic surface with an extremely high static water contact angle (CA) of 173.6° ± 1.7°. This superhydrophobic surface could be converted into a superhydrophilic surface with a water CA of nearly 0° by irradiating it with ultraviolet (UV) light, which induced photocatalytic decomposition of the ODP SAM. A superhydrophobic–superhydrophilic pattern with an extremely high wettability contrast (a water CA difference of over 170°) could be fabricated on the ODP-modified TiO 2 surface by area-selective UV irradiation through a photomask. This is the report of the TiO 2 -based superhydrophobic–superhydrophilic pattern with a water CA difference of over 170°, and it may be possible to use such patterns for various applications.

Injectable systems can be used in minimally invasive surgical applications. Although chitosan-glycerophosphate hydrogel systems are biodegradable and biocompatible, the long periods of time required for their effective gelation have severely limited their clinical application. The challenges currently facing researchers in this field are therefore focused on shortening the gelation time and biocompatibility of these materials to develop hydrogels suitable for clinical application. Chitosan and γ-glycidoxypropyltrimethoxysilane (GPTMS) hybrids have recently demonstrated good cytocompatibility with respect to human osteoblastic cells (MG63) and human bone marrow cells. Although these precursor sols could form gels under physiological conditions, they required neutralization with a sodium hydroxide solution. In this study, the chitosan-GPTMS hybrid systems were neutralized with glycerophosphate to prepare injectable hydrogels. The results revealed that the gelation time of the hydrogels could be controlled by the amount of GPTMS in the precursor sols. The in vitro cytocompatibility of the hydrogels were evaluated in terms of the proliferation of MG63 cells cultured either directly onto the hydrogels or indirectly onto the cell culture plate under a hydrogel insert. In the former case, the cells showed good attachment and proliferated for up to 7 days. Similar results were observed in the in direct culture. These results suggest that this new chitosan-GPTMS hydrogel could potentially be used as an injectable biomaterial in clinical applications.

Objectives The functional monomer 10-methacryloxydecyl dihydrogen phosphate (10-MDP), recently used in more self-etch adhesives, chemically bonds to hydroxyapatite (HAp) and thus tooth tissue. Although the interfacial interaction of the phosphoric-acid functional group of 10-MDP with HAp-based substrates has well been documented, the effect of the long carbon-chain spacer of 10-MDP on the bonding effectiveness is far from understood. Methods We investigated three phosphoric-acid monomers, 2-methacryloyloxyethyl dihydrogen phosphate (2-MEP), 6-methacryloyloxyhexyl dihydrogen phosphate (6-MHP) and 10-MDP, that only differed for the length of the carbon chain, on their chemical interaction potential with HAp and dentin, this correlatively using X-ray diffraction (XRD) and transmission electron microscopy (TEM). Commercial 6-MHP and 10-MDP containing adhesives were investigated as well. Results XRD revealed that on HAp only 10-MDP produced monomer-calcium salts in the form of ‘nano-layering’, while on dentin all monomers produced ‘nano-layering’, but with a varying intensity in the order of 10-MDP > 6-MHP > 2-MEP. TEM confirmed that 10-MDP formed the thickest hybrid and adhesive layer. XRD and TEM revealed ‘nano-layering’ for all commercial adhesives on dentin, though less intensively for the 6-MHP containing adhesive than for the 10-MDP ones. Significance It is concluded that not only the phosphoric-acid group but also the spacer group, and its length, affect the chemical interaction potential with HAp and dentin. In addition, the relatively strong ‘etching’ effect of 10-MDP forms more stable monomer-Ca salts, or ‘nano-layering’, than the two shorter carbon-chain monomers tested, thereby explaining, at least in part, the better bond durability documented with 10-MDP containing adhesives.

Organic-inorganic hybrids of poly(dimethyl siloxane), gelatin, and chitosan with such silanes as tetraethoxysilane and 3-glycidoxytriethoxysilane are derived via the sol-gel routes. Their biomedical applications are discussed from biomimetic deposition of bone-like apatite, cell culture, and in vivo behavior.

The silica gels, derived from water glass solution with pH adjusted at 3.0 and 9.9, were revisited to investigate their constitution, although water glass has been studied for last tens of decades on gelation. Solid-state nuclear magnetic resonance spectroscopy was applied to the nuclei 1H and 29Si, by the use of magic angle spinning (MAS), 1H → 29Si CP-MAS (CP: cross-polarization), and modern techniques such as 2D HETCOR (two dimensional heteronuclear correlation), and variable-contact time CP techniques. Gelation time (tgel) showed U-letter shape dependence on pH. All gels consisted of Qn groups (n: 2, 3, and 4), where Qn stands for a silicate unite [(O1/2)nSi (–O−)4−n] (n: 0–4). The analysis of the 1H → 29Si CP kinetics and 1H-29Si HETCOR spectra elucidated the presence of four kinds of 1H nuclei, i.e., those giving a peak at 6.9 ppm in chemical shift δ: 1H–OSi hydrogen bonded to H2O molecules; one at 4.3 ppm: 1H of adsorbed water molecules, hydrogen-bonded to the silanol groups; one at 1.7 ppm: 1H–OSi confined in the gel lattice, including that forming aggregations like Si–OH/NaO–Si; and one at 4.2 ppm: 1H of water molecules on the outermost hydration layer.

The treatment of peripheral nerve injuries is still one of the most challenging tasks in neurosurgery, as functional recovery is rarely satisfactory in these patients. The concept behind the use of biodegradable nerve guides is that no foreign material should be left in place after the device has fulfilled its task, so as to spare a second surgical intervention. In a previous study, flexible and biodegradable chitosan-γ-glycidoxypropyltrimethoxysilane (GPTMS) hybrid membranes exhibited better cytocompatibility in terms of osteoblastic cells than chitosan membrane. Porous chitosan hybrid membranes, derived by freeze-drying the hybrid gels, showed that the cells were attached and proliferated both on the surface and into pores. The aim of the present study was to evaluate the influence of these chitosan hybrid membranes in terms of their inflammatory response and remodeling of connective tissue during wound-healing processes before use as a periphery nerve graft. The porous chitosan hybrid membranes showed good biocompatibility and improved posttraumatic axonal regrowth and functional recovery.

Silica gel macrospheres of 2~4 mm in size, and wrapped with Ca-alginate chelate film were prepared as the substrate for hydroxyapatite coating layer, using water glass as the silica source. Those Ca-SiO2 macrospheres were soaked in a 1:1 (volume) mixture of ethanol and 0.1 M Na2HPO4 to deposit hydroxyapatite layer (HAp-SiO2 macrospheres). Adsorption of bovine serum albumin and egg lysozyme on those Ca-SiO2 and HAp-SiO2 macrospheres under physiological pH (7.2) was well correlated to the Langmuir-type adsorption equation. The electrostatic interactions between the protein molecules and those macrospheres well interpret the adsorption isotherms, while the mesopores in the Ca-SiO2 contributed to some extent. A multi-layer adsorption model was proposed.

Implant surfaces must sometimes be modified to form strong bonds to host tissues. The method of depositing an anatase layer on chemically pure titanium by chemical oxidation with H2O2 and subsequent calcination (CHT) is known to deposit apatite under physiological conditions; it thus exhibits bone-bonding ability. UV irradiation should affect the bonding ability because the CHT anatase layer would experience certain chemical modifications, such as a decrease or an increase in the number of TiOH and TiO(H)Ti sites; these sites are considered active sites for apatite nucleation. When in vitro apatite deposition was examined, using Kokubo's simulated body fluid, UV irradiation in air reduced the apatite-forming ability of the CHT anatase layer, and UV irradiation on the samples in water enhanced the ability. These results were correlated to changes in the TiOH and TiO(H)Ti sites, as determined by O 1s X-ray photoelectron spectroscopy. Analysis of the number and size of the semi-spherical apatite particles and their surface coverage led to a model: proper assembly of the TiOH and TiO(H)Ti sites should only give rise to the induction of apatite nucleation, analogous to topotaxy effects. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 712–719, 2013.

A recently developed “GRAPE® technology” provides titanium or titanium alloy implants with spontaneous apatite-forming ability in vitro, which requires properly designed gaps and optimum heat treatment in air. In this study, pure titanium pieces were thermally oxidized in air and pre-irradiated by UV-light under different environmental conditions such as in air or in ultra-pure water before aligning pairs of specimens in the GRAPE® set-up, i.e., two pieces of titanium substrates were aligned parallel to each other with optimum gap width (spatial design). Then, they were soaked in Kokubo’s simulated body fluid (SBF, pH7.4, 36.5°C) for 1-2 days to clarify how the UV-light pre-irradiation affects the in vitro apatite nucleation on the substrates under the specific spatial design. UV-light pre-irradiation in water led to the deposition of a large number of apatite particles within 1 day, and showed apatite X-ray diffraction, although UV-light pre-irradiation in air and non-pretreated specimens gave the deposition of a few apatite particles and did not show any apatite X-ray diffraction. These results indicated that the rate of primary heterogeneous nucleation of apatite increased by UV-light pre-irradiation in ultra-pure water. TF-XRD patterns of the surface of the substrates thermally oxidized in air at 500°C showed the peak at 2θ = 27º assignable to the 110 diffraction of rutile phase of titanium dioxide (ICDD-JCPDS data #21-1276). Previous studies reported that the primary heterogeneous nucleation must be induced by Ti-OH groups on titanium oxide layer. Probably, the UV-light pre-irradiation in ultra-pure water can increase the number of Ti-OH groups on the surface, resulting in accelerated primary heterogeneous nucleation of apatite.

Chitosan-GPTMS (γ-Glycidoxypropyltrimethoxysilane) hybrid hydrogels were synthesized with β-glycerophosphate (β-GP) as the additive agent. Chitosan-GPTMS sols were fluid at room temperature and transformed to hydrogel at 36.5°C in several min. The gelation time of the hydrogels was shortened by the addition of GPTMS. From NMR experiments, this gelation behavior depended on some factors, namely, electrostatic interaction between the phosphate groups of β-GP and the amino groups of chitosan chains, crosslinking between the epoxy groups of GPTMS and the amino groups of chitosan, and polycondensation of the methoxy groups of GPTMS. The Si(IV) released from the hydrogels promoted the cell adhesion and ALP activity of osteoblastic cells MG63.

Silicate–collagen hybrid fibril sheets were obtained using 3-glycidoxypropyl trimethoxysilane (GPTMS) as a novel cross-linker for type I collagen fibrils. BMP-2 was introduced in the hybrid sheets to stimulate cell proliferation and differentiation. Scanning electron microscopy images indicated that the resultant sheets were nanofibrous and porous. Transmission electron microscopy images showed that each hybrid fibril maintained a typical periodic unit of 60–70 nm. Compared to fibrils cross-linked by a conventional carbodiimide agent, the present hybrid fibrils were much more resistant against type I collagenase degradation. When soaked in BMP-2 solution, the hybrid sheets easily adsorbed BMP-2 and exhibited sustained release for BMP-2. Osteoblast-like MC3T3-E1 cells were well attached to and proliferated on the hybrid sheets. The proliferation and differentiation of these cells were enhanced to form collagen fibrils due to BMP-2 release.

This study proposes a new guideline for designing biodegradable apatite ceramics. Boron-containing hydroxyapatite (BHAp) particles were prepared by a high-temperature solid-state reaction processing method and were characterized in terms of their chemical composition, apatite lattice defects and in vitro biodegradability. Solid-state nuclear magnetic resonance analysis showed that boron-incorporation into hydroxyapatite (HAp) derived by thermo-chemical reactions between borate and calcium phosphate phases led to disordered phases (BCaP) of a CaO–P2O5–B2O3–OH system covering the crystalline HAp core. X-ray diffraction analysis indicated that the BCaP phase must consist mainly of a crystalline oxyboroapatite (OBAp) phase. An in vitro biodegradability test showed that BHAp degraded quicker than HAp or β-tricalcium phosphate. The biodegradability of BHAp particles can be controlled by boron incorporation into a HAp lattice leading to the formation of a disordered OBAp phase.

Previous research, in which the bonding effectiveness of the 3 self-etch monomers HAEPA, EAEPA, and MAEPA was determined, showed that MAEPA was most effective. In this study, the molecular interactions of these monomers with hydroxyapatite and dentin were investigated by combining x-ray diffraction, infrared spectroscopy, and scanning electron microscopy. We tested the null hypothesis that the bonding performance of these monomers does not correlate to the formation of monomer-calcium salts and to hydrolytic stability of these monomer-calcium complexes. Monomer/ethanol/water solutions were prepared and applied to synthetic hydroxyapatite and dentin. While HAEPA and EAEPA dissolved dentin considerably and deposited unstable calcium-phosphate salts (DCPD), MAEPA formed hydrolysis-resistant monomer-calcium salts that remained attached to the dentin surface even after being washed. The chemical stability of the monomer-Ca salts was thought to contribute in particular to the bond durability, but this study shows that the formation of stable monomer-calcium salts also enhances the ‘immediate’ bonding performance of self-etch adhesives.

A flow-micro-reactor system was employed to fabricate hydroxyapatite (HAp) in order to mimic the interface between calcium and phosphate solutions on a wet chemical procedure. The mixing ratio of calcium nitrate tetrahydrate and diammonium hydrogenphosphate solution was set to the stoichiometric atomic ratio HAp, 1.67, while pH value of the product suspension was varied from 6.4 to 10.0. The product morphology was changed from nano-sheet type to nano-particle type via nano-rod one, while their size was decreased from 100–500 nm to 50 nm. All as-prepared samples, irrespective of pH value of the resultant suspension, consisted of HAp, predominant phase, octacalcium phosphate (OCP), and dicalcium phosphate dihydrate (DCPD) or dicalcium phosphate anhydrate (DCPA). A batch system using the same solutions yielded very similar results, which confirmed that the reactions in this micro-reactor well reproduced a large-scale mixing system. Calcining sample obtained from pH 6.4 suspension for 2 h at lower temperatures (

Although decayed/fractured teeth can be reconstructed minimally invasively and nearly invisibly using adhesive technology, the clinical longevity of dental composite restorations is still too short. Water sorption is thought to be the principal cause of destabilization of the biomaterial–tooth bond. However, the actual mechanisms of interfacial degradation are far from understood. Here we report how nano-controlled molecular interaction at the biomaterial–hard tissue interface can improve bond durability. The use of functional monomers with a strong chemical affinity for the calcium in hydroxyapatite is essential for long-term durability. Correlative X-ray diffraction and solid-state nuclear magnetic resonance disclosed a time-dependent molecular interaction at the interface with stable ionic bond formation of the monomer to hydroxyapatite competing in time with the deposition of less stable calcium phosphate salts. The advanced tooth–biomaterial interaction model gives not only an insight into the mechanisms of bond degradation, but also provides a basis to develop functional monomers for more durable tooth reconstruction.

Chitosan–γ-glycidoxypropyltrimethoxysilane (GPTMS)–tetraethoxysilane (TEOS) hybrid membranes were prepared by the sol–gel method. The effects of Si(IV) released from them on cell proliferation and differentiation were examined in terms of cell metabolic activity and the alkaline phosphatase (ALP) activity of MG63 osteoblastic cells. The amount of Si(IV) released from the hybrid membranes increased with the TEOS content. The released Si(IV) inhibited cell proliferation but promoted cell differentiation. Thus, the osteocompatibility of the chitosan hybrid membranes in the chitosan–GPTMS–TEOS system can be controlled by the amount of Si(IV) released from them when they are applied to cell culture.

Agglomerated amino-modified silica nanoparticles were prepared from a novel Stober-like precursor system consisting of aminopropyltriethoxysilane (APTES), tetraethoxysilane (TEOS), ethanol, and water where the molar ratio APTES/TEOS was 0, 0.1, 1.0, and 2.0, and the molar ratio H2O/-SiOC2H5 was about 20 to 60, or great excess amounts of H2O were employed. APTES catalyzed the hydrolysis and condensation of both silanes. 29Si magic angle spinning nuclear magnetic resonance spectra confirmed that the particles consisted of Qn species (Si(OSi)n(OH)4−n; n=2, 3, 4) and Tn species (NH2(CH2)3–Si(OSi)n(OH)3−n; n=2, 3). The APTES content in the precursor solutions controlled the agglomerating spherical particle size and morphology: 0.1 in the ratio APTES/TEOS led to almost independent spheres of 300–400 nm, while the larger ratios 1 and 2 led to ∼250 and ∼150 nm spheres, respectively, that were largely agglomerated and some were fused to look like peanut-shells. When soaked in Kokubo's simulated body fluid, those amino-modified particles deposited apatite. The mechanisms of particle formation and apatite deposition were discussed in terms of an intraparticle hydrated layer.

Nuclear magnetic resonance (NMR) has been used for a detailed investigation of the borate incorporation in apatitic biomaterials prepared by high-temperature solid-state reaction sintering. The NMR...

Multilayer anatase films were coated by sol–gel technology on various substrates such as stainless-steel, alumina, and glass, respectively. Their in vitro apatite-forming ability was examined by immersion in Kokubo's simulated body fluid (SBF; pH 7.4, 36.5 °C). Although on anatase layer on alkali-free glass apatite was deposited within 7 d, no apatite was found on anatase deposited onto stainless steel, alumina or glass substrates within 7 d to prove they were bioinert. X-ray photoelectron spectroscopy was able to detect chromium, aluminum, or sodium on the surface of the anatase films. This indicated that these ions possibly inhibited the in vitro apatite-forming ability.

Amino-modified TiO2 particles were derived from precursor mixtures of tetraethylorthotitanate and aminopropyltriethoxysilane (APTES) that both were dissolved in ethanol/water solution. Size, morphology, crystalline structures, and formation mechanism of the particles were discussed in terms of the APTES amount and the pH value in the solution. The addition of APTES resulted in amorphous amino-modified TiO2 particles. The low crystallinity in the final particles was attributed to the polar amino groups.

We attempted to prepare chitosan-silicate hybrid for use in a medical application and evaluated the physico-chemical properties and osteocompatibility of the hybrids as a function of gamma-glycidoxypropyltrimethoxysilane (GPTMS) concentration. Chitosan-silicate hybrids were synthesized using GPTMS as the reagent for cross-linking of the chitosan chains. Fourier transform infrared spectroscopy, (29)Si CP-MAS NMR spectroscopy and the ninhydrin assay were used to analyze the structures of the hybrids, and stress-strain curves were recorded to estimate their Young's modulus. The swelling ability, contact angle and cytocompatibility of the hybrids were investigated as a function of the GPTMS concentration. A certain fraction of GPTMS in each hybrid was linked at the epoxy group to the amino group of chitosan, which was associated with the change in the methoxysilane group of GPTMS due to hybridization. The cross-linking density was around 80% regardless of the volume of GPTMS. As the content of GPTMS increased, the water uptake decreased and the hydrophilicity of the hybrids increased except when the content exceeded amolar ratio of 1.5, when it caused a decrease. The values of the mechanical parameters assessed indicated that significant stiffening of the hybrids was obtained by the addition of GPTMS. The adhesion and proliferation of the MG63 osteoblast cells cultured on the chitosan-GPTMS hybrid surface were improved compared to those on the chitosan membrane, regardless of the GPTMS concentration. Moreover, human bone marrow osteoblast cells proliferated on the chitosan-GPTMS hybrid surface and formed a fibrillar extracellular matrix with numerous calcium phosphate globular structures, both in the presence and in the absence of dexamethasone. Therefore, the chitosan-GPTMS hybrids are promising candidates for basic materials that can promote bone regeneration because of their controllable composition (chitosan/GPTMS ratio).

We report on the effect of using a spatial gap on heterogeneous nucleation on the surface of thermally oxidized titanium substrates. Induction of heterogeneous nucleation of bone-like hydroxyapatite (BHAp) was evaluated in the spatial gaps between substrates that were thermally oxidized at temperatures of 100-800°C on exposure to a simulated body fluid (SBF). After soaking in a SBF for 7 d, BHAp spontaneously deposited inside the gap on the surface of samples that were thermally oxidized at temperatures above 400°C, but not on samples that were thermally oxidized at temperatures of 300°C or less. Among the substrates studied, BHAp particles were most readily deposited inside the gap on the surface of the samples that were thermally oxidized at 400°C after soaking in an SBF. A smaller gap led to a higher number of BHAp particles being deposited on the surface of the samples that were thermally oxidized at 400 or 500°C. Our results suggest that the formation of BHAp in a SBF is dependent on the temperature during thermal oxidization, and also on the spatial gap between the samples. The ease of formation of BHAp on thermally oxidized titanium increases with increasing thickness of the rutile phase and the number of Ti-OH groups, which are produced during the thermal oxidization process. In addition to the surface structure of the substrates, the spatial gap is regarded as an important parameter for enhancing the deposition of BHAp. Since the formation of BHAp allows osteoconduction to occur after implantation in a bony defect, it is possible to design titanium-based implants with a high biological affinity to bone by processing using an appropriate spatial design of the substrate.

Apatite formation on the surface of titanium and its alloys is effective for inducing osteoconductivity when implanted in bony defects. The aim of this study was to investigate the effects of thermal oxidation on apatite formation in macro-grooves on Ti-15Zr-4Ta-4Nb. Thermal oxidation at 500 and 600 degrees C in air led to modification of the Ti-15Zr-4Ta-4Nb surface to rutile phase titanium oxide. Ti-15Zr-4Ta-4Nb thermally oxidized at 500 degrees C in air showed no changes in metallographic structure, but not at 600 degrees C. After soaking in a simulated body fluid for 7days, the formation of apatite could be observed on the internal surfaces of macro-grooves 500mum deep and wide on Ti-15Zr-4Ta-4Nb thermally oxidized at 500 and 600 degrees C in air. These results indicate the potential for osteoconductivity of Ti-15Zr-4Ta-4Nb without changing its metallographic structure, by fabricating only the macro-grooves, i.e., spatial design, and by performing thermal oxidation at 500 degrees C.

The incorporation of ions in the lattice of hydroxyapatite alters significantly its structure. Particularly, if anions such as trigonal borate units are accommodated in the lattice severe distortions must occur around the substitution site because of different geometric shape, electric charge and anion size. Solid-state NMR has been used to investigate this problem in detail for a hydroxyapatite sample synthesized by high temperature solid state reaction. The results clearly verify the existence of network distortions. Indeed, only about 1/3 of the total phosphate content forms crystalline hydroxyapatite (also found in XRD) whereas the residual amount is contained in two different phosphate sites with 31P chemical shifts of 5.5 ppm and 2.3 ppm, but broad resonances lines suggesting disorder. Furthermore, a novel proton signal at -0.6 ppm was found which is directly associated with the borate incorporation. No specific correlation of the two structurally different borate units with the two phosphate groups is found.

Prepared via Stober-type sol–gel routes were three types of silica particles of Si–OH as well as hydrogen bonding interactions among them. In addition, the Ca–silica and core-shell silica deposited apatite in Kokubo’s simulated body fluid. Thus, the present Ca–silica and polymer-coated silica particles were suggested to be applicable to injectable bone fillers for bone generation.

Titania (anatase) gel powders were prepared by peptizing commercially available titania sols and heating them at temperatures up to 700 degrees C, as candidates for bilirubin adsorbents for blood purification therapy. Those titania particles were in contact with a protein solution containing bilirubin and bovine serum albumin that mimics the blood of bilirubinemia patients. The amount of free or direct bilirubin in the solution insignificant. Indirect bilirubin or a bilirubin complex with albumin was adsorbed on the anatase powders, the primary particle size of which was as large as or larger than the size of an albumin molecule. The surface charge and surface charge density were only minor factors in controlling the indirect bilirubin adsorption. The present results indicated that the size of primary particles and hydrophobicity were significant for the sol-derived anatase in terms of bilirubin adsorption, and both were controllable by the heating temperature and the time period.

In the brain after infarction or trauma, the tissue becomes pannecrotic and forms a cavity. In such situation, a scaffold is necessary to produce new tissue. In this study, we implanted a new porous gelatin-siloxane hybrid derived from gelatin and 3-(glycidoxypropyl) trimethoxysilane (gelatin-GPTMS) scaffolds into a brain defect, and investigated whether it makes a new brain tissue. In addition, vascular endothelial growth factor (VEGF) was added on gelatin- GPTMS scaffolds and its effect on tissue regeneration was examined. At 30 days after the implantation, the marginal territory of the scaffolds became occupied by newly formed tissue. Immunohistochemical analysis revealed that the new tissue was constituted by endothelial, astroglial and microglial cells, some of which were labeled for bromodeoxyuridine (BrdU). Addition of VEGF promoted numbers of these cells. Thus, combination of gelatin-GPTMS scaffolds and VEGF is preferable for brain regeneration.

Chitosan–silicate hybrids with 3D porous structures were prepared with freeze-drying precursor solutions derived from chitosan and γ-glycidoxypropyltrimethoxysilane (GPTMS). They were formed easily in any shape, such as sheets, pellets, disks, granules, and even roll-cakes. The pore size was strongly dependent on the freezing temperature: lower freezing temperature resulted smaller pores, about 110 μm for the hybrids frozen at −20 °C, and about 50 μm for those at −85 °C. The pore size was little dependent on the GPTMS content. In contrast, the GPTMS content affected porosity a littlie: ∼80% for chitosan, and ∼90% for the GPTMS-containing hybrids. Thus, their porous microstructure was controllable due to the freezing temperature and composition. MG63 osteoblastic cells were cultured up to 7 days on the porous hybrids. The cells adhered on the pore walls, proliferated, and migrated deep into the pore structure. It was thus concluded that the present chitosan–silicate hybrids were promising for tissue engineering scaffold applications.

Titania layer is deposited on polyethylene substrates when they are soaked in TiOSO4/H2O2 solution and aged in hot water. The aging in hot water promoted the precipitation of anatase and rutile in the surface layer, indicating that cleavage and recombination of the Ti-O-Ti bond took place. The Ti-OH functional groups were rearranged and emerged accompanying the structure relaxation in the layer. Moreover, the aging in hot water enhanced crystalline of titania and then obtained well apatite-forming ability on the polyethylene substrates in SBF. This was accounted for by the removal of residual impurities due to TiOSO4/H2O2 treatment. They had an anatase/rutile dual layer microstructure: the dense bottom layer predominantly consisted of rutile, while the upper layer consisted of loosely packed aggregation of anatase particles. The titania deposition was the results of compromise among two conflicting processes: 1) hydrolysis of titanium oxysulfate to yield either soluble titanol-complexes or titania, 2) dissolution of the titania under the presence of hydrogen peroxide to yield similar complexes or compounds. Various soaking periods were carried out to investigate the dissolution-deposition equilibrium in the solution. Anatase/rutile dual layers were thus deposited on titanium and polyethylene substrates when they were soaked in TiOSO4/H2O2 solution and aged in hot water. The proper soaking time in the treating solution is the other key factors to control the formation of dense titania layers. The resulted titania layers have apatite-forming ability.

Among the clinical treatments of Familial Hyper cholesterolemia patients to reduce the concentration of low density lipoprotein (LDL), blood purification therapy is most suitable in which a blood-compatible adsorbent is employed. In the present study, alumina powders were prepared via a sol-gel route to develop a LDL-adsorbent Aluminum tri2-propoxide was hydrolyzed and subsequently calcined up to 1200 degrees C. Surface charge density and pore size distribution were measured, and the phases were identified. The alumina calcined above 400 degrees C had excellent blood compatibility in terms of endogenous clotting parameters, i.e., partial thromboplastin time: (PTT), prothrombin time: (PT), and the amount of fibrinogen: (Fib). The amount of LDL-adsorption (DeltaW(LDL)) increased with the calcining temperature, showing a good linear correlation to surface charge density. The 1200 degrees C sample consisted only of alpha-alumina, and was greatest in DeltaW(LDL). All samples involved pores smaller than 20 nm but not the pores large enough to accommodate LDL molecules (20-25 nm). From those results, it was concluded for the present alumina particles that the surface charge density was the primary factor and that the chemical activity of alpha-alumina also contributed to the excellent LDL-adsorption for the 1200 degrees C sample, while entrapping LDL in the pores was not an active mechanism.

Surface properties of implants are the keys for ensuring their long-lasting anchorage to the tissue. This study aims to develop a novel implant surface microstructure with high biocompatibility and ability of guided tissue formation. By a photolithography method, gold (Au) grids (1 x 1 mm(2) square lattices, 10 mum in grid-line width) were deposited on titanium substrates. They were oxidized with H(2)O(2) solution to yield titania (anatase) layer, and the Au grid formed channels due to larger molar volume of anatase than Ti. L-Cysteine and type I collagen were then immobilized on them to yield the target substrates, CHT-Au-cys-col. Apatite deposited within 3 days when they were soaked in Kokubo's simulated body fluid, regardless of the protein coating, but not on the bottom of the Au channel. Osteoblast-like MC3T3-E1 cells were cultured on the CHT-Au-cys-col substrates, showing that (1) the cysteine-collagen coating promoted cell attachment and proliferation, and (2) the Au channels were filled with the cells which were aligned along the channel direction and were connected to the neighboring cells as well as attached to the channel wall with cytoplasmic extensions. The results thus ensured filopodial guidance for the substrates.

Hydroxyapatite formation on the surface of materials in the body is an essential condition for demonstrating osteoconduction after implantation in bony defects. This paper reports a technique for providing hydroxyapatite formation properties to titanium metals by using specially designed surface topography followed by thermal oxidation. Two pieces of titanium thermally oxidized at 400 � C were set together in a V-shape with varied mouth opening. They showed the formation of hydroxyapatite on both facing surfaces after exposure to a simulated body fluid (SBF), when the gap height was approximately less than 600 mm. Moreover, pure titanium specimens with macro-grooves less than 1000 mm in depth and 800 mm in width were able to form hydroxyapatite deposits in SBF within 604.8 ks, after they were thermally oxidized at 400 � C for 3.6 ks. Hydroxyapatite also formed on the internal surfaces of macro-grooves made in Ti-15-Zr-4Ta-4Nb within 604.8 ks of soaking in SBF, after the sample was thermally oxidized at 500 � C for 3.6 ks, whereas it was not deposited on alloy made of Ti-6Al-4V extra low interstitial processed in the same way. These findings indicate that titanium and its alloys can be conferred with hydroxyapatite-forming ability, i.e. osteoconduction, within a controlled spatial gap and thermal oxidation. We conclude that bioactive titanium substrate showing osteoconduction can be produced by using a specially designed surface topography followed by thermal oxidation at an appropriate temperature.

Ultraviolet (UV) light was irradiated in air for 1 h on titania (rutile) films prepared by thermal oxidation of titanium substrates from 300°C up to 800°C, coded as HT300UV, HT400UV, HT500UV, HT600UV, HT700UV, and HT800UV, respectively. All samples were then soaked in a simulated body fluid (SBF, Kokubo solution) and their in vitro apatite-forming ability was evaluated. It was found that bone-like apatite particles were deposited on HT500UV, HT600UV, and HT700UV within 7 d whereas that was not the case with others during the same period. Moreover, the apatite particles were deposited more on HT500UV than on the others. Therefore, the ultraviolet light irradiation enhanced the in vitro apatite-forming ability of the thermally oxidized titanium.

Boron-containing hydroxyapatite (BHAp) particles were synthesized by the wet chemical processing method and subsequent thermal treatment at the temperature ranging from 700-1200°C, and examined the effect of boron introduction on the microstructure of BHAp. The local structure around boron and phosphorus in the BHAp was analyzed by solid-state magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy. The heat-treatment above 700°C induced the thermal decomposition of HAp to β-TCP and then the chemical reaction between HAp and B(OH)3 was induced above 900°C, resulting in the formation of boron-substituted HAp particles accompanied by the formation of β-TCP and its transformation to α-TCP above 1200°C.

Apatite formation on the surface of materials in body environment is an essential condition to show osteoconduction after implantation in bony defects. This study reports the novel technique for providing the apatite-forming ability to titanium metals by only controlling the spatial gap and thermal oxidation. Two pieces of titanium thermally oxidized at 400 °C were set together like V-letter with varied mouth opening. They showed the formation of apatite on both facing surface after exposure to a simulated body fluid (SBF) proposed by Kokubo and his colleagues, when the gap was less than approximately 600 μm. Moreover, specimens with micro-grooves of 500 μm in depth and 200-1000 μm in width was able to form apatite in SBF with in 7 days, after they were thermally oxidized at 400 oC. These results indicated that the titanium metals were provided with apatite-forming ability, i.e. osteoconduction, due to controlled gap with thermally oxidized surface. Hence, we conclude that bioactive titanium substrate showing osteoconduction can be produced by designed machining followed by thermal oxidation at an appropriate temperature.

Previous in vitro studies confirmed an improved cytocompatibility of chitosan-silicate hybrid membranes over chitosan membranes. The main goal of this study was to assess the in vivo histocompatibility of both membranes through subcutaneous implantations at different time periods, 1 week, 1, 2 and 3 months, using a sheep model. Chitosan membranes elicited an exuberant inflammatory response and were consequently rejected. The hybrid chitosan membranes were not rejected and the degree of inflammatory response decreased gradually until the third month of implantation. Histological evaluation also showed that these membranes can be resorbed in vivo. This study demonstrates that the incorporation of silicate into the chitosan solution improves its histocompatibility, indicating that the hybrid chitosan-silicate membranes are suitable candidates to be used in clinical applications.

Porous chitosan-silicate hybrids were prepared by freeze-drying the precursor sol solutions synthesized from chitosan and 3-glycidoxypropyltrimethoxysilane (GPTMS). Degradability of and the release of cytochrome C in to phosphate buffer saline solution (PBS) were examined as a function of the GPTMS content. The hybrids were less degradable with larger GPTMS contents, and the cytochrome C release profile was so controllable as to give either burst release or slow one due to the GPTMS content. Thus, the present porous chitosan-silicate hybrids were considered applicable to drug delivery systems.