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Organosilica hybrid particles were derived for the first time from a catalyst-free neutral sol–gel system of vinyltrimethoxysilane, tetramethoxysilane, ethanol, and water and consisted of Tspecies (CH2CH–Si(–O–Si)n(OH, OCH3)3−n, n= 2 and 3) and Qspecies (Si(–O–Si)n(OH, OCH3)4−n, n= 2, 3, and 4). After combined with poly(methylmethacrylate) and CaCl2, they induced deposition of bioactive apatite in the Kokubo's simulated body fluid and are applicable for bone regeneration. [ABSTRACT FROM AUTHOR]

Biomedical applications of poly(ether ether ketone) (PEEK) are hindered by its inherent bioinertness and lack of osseointegration capability. In the present study, to enhance osteogenic activity and, hence, the osseointegration capability of PEEK, we proposed a strategy of combined phosphate and calcium surface-functionalization, in which ozone-gas treatment and wet chemistry were used for introduction of hydroxyl groups and modification of phosphate and/or calcium, respectively. Surface functionalization significantly elevated the surface hydrophilicity without changing the surface roughness or topography. The cell study demonstrated that immobilization of phosphate or calcium increased the osteogenesis of rat mesenchymal stem cells compared with bare PEEK, including cell proliferation, alkaline phosphatase activity, and bone-like nodule formation. Interestingly, further enhancement was observed for samples co-immobilized with phosphate and calcium. Furthermore, in the animal study, phosphate and calcium co-functionalized PEEK demonstrated significantly enhanced osseointegration, as revealed by a greater direct bone-to-implant contact ratio and bond strength between the bone and implant than unfunctionalized and phosphate-functionalized PEEK, which paves the way for the orthopedic and dental application of PEEK. [ABSTRACT FROM AUTHOR]

This study was aimed to investigate the osseointegration ability of poly(ether ether ketone) (PEEK) implants with modified surface roughness and/or surface chemistry. The roughened surface was prepared by a sandblast method, and the phosphate groups on the substrates were modified by a two-step chemical reaction. The in vitro osteogenic activity of rat mesenchymal stem cells (MSCs) on the developed substrates was assessed by measuring cell proliferation, alkaline phosphatase activity, osteocalcin expression, and bone-like nodule formation. Surface roughening alone did not improve MSC responses. However, phosphorylation of smooth substrates increased cell responses, which were further elevated in combination with surface roughening. Moreover, in a rabbit tibia implantation model, this combined surface modification significantly enhanced the bone-to-implant contact ratio and corresponding bone-to-implant bonding strength at 4 and 8 weeks post-implantation, whereas modification of surface roughness or surface chemistry alone did not. This study demonstrates that combination of surface roughness and chemical modification on PEEK significantly promotes cell responses and osseointegration ability in a synergistic manner both in vitro and in vivo. Therefore, this is a simple and promising technique for improving the poor osseointegration ability of PEEK-based orthopedic/dental implants. [ABSTRACT FROM AUTHOR]

Three commercially available artificial bone substitutes with different compositions, hydroxyapatite (HAp; Neobone®), carbonate apatite (CO3Ap; Cytrans®), and β-tricalcium phosphate (β-TCP; Cerasorb®), were compared with respect to their physical properties and tissue response to bone, using hybrid dogs. Both Neobone® (HAp) and Cerasorb® (β-TCP) were porous, whereas Cytrans® (CO3Ap) was dense. Crystallite size and specific surface area (SSA) of Neobone® (HAp), Cytrans® (CO3Ap), and Cerasorb® (β-TCP) were 75.4 ± 0.9 nm, 30.8 ± 0.8 nm, and 78.5 ± 7.5 nm, and 0.06 m2/g, 18.2 m2/g, and 1.0 m2/g, respectively. These values are consistent with the fact that both Neobone® (HAp) and Cerasorb® (β-TCP) are sintered ceramics, whereas Cytrans® (CO3Ap) is fabricated in aqueous solution. Dissolution in pH 5.3 solution mimicking Howship's lacunae was fastest in CO3Ap (Cytrans®), whereas dissolution in pH 7.3 physiological solution was fastest in β-TCP (Cerasorb®). These results indicated that CO3Ap is stable under physiological conditions and is resorbed at Howship's lacunae. Histological evaluation using hybrid dog mandible bone defect model revealed that new bone was formed from existing bone to the center of the bone defect when reconstructed with CO3Ap (Cytrans®) at week 4. The amount of bone increased at week 12, and resorption of the CO3Ap (Cytrans®) was confirmed. β-TCP (Cerasorb®) showed limited bone formation at week 4. However, a larger amount of bone was observed at week 12. Among these three bone substitutes, CO3Ap (Cytrans®) demonstrated the highest level of new bone formation. These results indicate the possibility that bone substitutes with compositions similar to that of bone may have properties similar to those of bone. [ABSTRACT FROM AUTHOR]

Carbonate apatite (CO3Ap) is an inorganic component of bone. This study aimed to compare the composition and tissue response to of CO3Ap (CO3Ap-DP) fabricated by the dissolution-precipitation reaction using calcite as a precursor and Bio-Oss®, which is widely used in orthopedic and dental fields as a synthetic bone substitute. X-ray diffraction and Fourier transform infrared results showed that CO3Ap-DP and Bio-Oss® were both B-type carbonate apatite with low crystallinity. The average sizes of CO3Ap-DP and Bio-Oss® granules were 450 ± 58 and 667 ± 168μ m, respectively, and their carbonate contents were 12.1 ± 0.6 and 5.6 ± 0.1 wt%, respectively. CO3Ap-DP had a larger amount of CO3 than Bio-Oss® but higher crystallinity than Bio-Oss®. When a bone defect made at the femur of rabbits was reconstructed with CO3Ap-DP and Bio-Oss®, CO3Ap-DP granules were partially replaced with bone, whereas Bio-Oss® remained at 8 weeks after implantation. CO3Ap-DP granules elicited a significantly larger amount of new bone formation at the cortical bone portion than Bio-Oss® at 4 weeks after the implantation. The results obtained in the present study demonstrated that CO3Ap-DP and Bio-Oss® showed different behavior even though they were both classified as CO3Ap. The CO3 content in CO3Ap played a more important role than the crystallinity of CO3Ap for replacement to bone and high osteoconductivity. [ABSTRACT FROM AUTHOR]

Abstract Although Ti bone scaffolds are widely used clinically as various hard-tissue scaffolds including dental implants, their limited initial osseointegration property is a significant disadvantage, which should be improved. A rough surface and the allied Ca ion release capability might improve initial osteointegration by enhancing the activity of osteoblasts, which dominates osseointegration. In this study, a calcite-coating method, as a Ca ion releaser, is introduced onto rough surfaces of the Ti scaffold by heat carbonation using calcium nitrate as the Ca source below the α-to-β phase transition temperature (~880 °C) of Ti. After this treatment, the Ti scaffolds become whiter with increasing the concentration of the calcium nitrate solution. X-ray diffraction (XRD) and spectroscopic measurements demonstrate that calcite is formed on the Ti scaffold after the treatment. Scanning electron microscopy (SEM) observations show numerous rhombohedral crystals with a size of several micrometers, densely covering the surface of the Ti scaffold, maintaining its rough surface structure. Optimization of the initial calcium nitrate solution concentration controls the amount of calcite coating onto the desired regions on the surface of the Ti scaffolds. The coating strength of the fabricated calcite is ~20 MPa, which is sufficient to resist implanting strength. Highlights • Calcite strongly and uniformly coating onto Ti surface could be fabricated by heat carbonation. • The coating strength is ~20 MPa, which is sufficient to resist implanting strength. • The coating amount of calcite could be easily controlled and optimized. [ABSTRACT FROM AUTHOR]

Interconnected porous calcium-deficient hydroxyapatite (cdHAp) blocks may be an ideal biomaterial to repair bone defects because of their greater similarity to human bone than that of sintered hydroxyapatite (HAp) with respect to calcium content and crystallinity. In particular, the interconnected pores in cdHAp may provide pathways for cell migration and tissue ingrowth. In this study, the feasibility of fabricating interconnected porous cdHAp blocks through the setting reaction of alpha-tricalcium phosphate (αTCP) spherical granules was investigated. It was found that regulation of cdHAp formation was important to fabricate interconnected porous cdHAp blocks. That is, cdHAp needed to precipitate preferentially at the contacting areas between αTCP spherical granules. Exposure of αTCP spherical granules to steam under appropriate pressure was effective for this purpose. When αTCP spherical granules were immersed in water at 100 °C, the setting reaction resulted in dense cdHAp blocks because of the free crystal growth of cdHAp in water. Therefore, steam was used to localize the water at the contacting areas between αTCP spherical granules, which was driven by the surface tension of the water. Without an applied load, no setting reaction was observed when αTCP spherical granules were exposed to steam at 100 °C for 12 h. In contrast, under a load of 20 MPa, cdHAp precipitated to bridge spherical granules, providing an interconnected porous cdHAp block. The porosity and diametral tensile strength of this block were approximately 63% and 1.5 MPa, respectively. [ABSTRACT FROM AUTHOR]

Calcium carbonate (CaCO 3 ) has been used as a bone substitute, and is a precursor for carbonate apatite, which is also a promising bone substitute. However, limited studies have been reported on the fabrication of artificial calcite blocks. In the present study, cylindrical calcite blocks (ϕ6 × 3 mm) were fabricated by compositional transformation based on dissolution–precipitation reactions using different calcium sulfate blocks as a precursor. In the dissolution–precipitation reactions, both CaSO 4 ·2H 2 O and CaSO 4 transformed into calcite, a polymorph of CaCO 3 , while maintaining their macroscopic structure when immersed in 1 mol/L Na 2 CO 3 solution at 80 °C for 1 week. The diametral tensile strengths of the calcite blocks formed using CaSO 4 ·2H 2 O and CaSO 4 were 1.0 ± 0.3 and 2.3 ± 0.7 MPa, respectively. The fabrication of calcite blocks using CaSO 4 ·2H 2 O and CaSO 4 proposed in this investigation may be a useful method to produce calcite blocks because of the self-setting ability and high temperature stability of gypsum precursors. [ABSTRACT FROM AUTHOR]

Amino-functionalized silica nanoparticles smaller than 200 nm in diameter were directly prepared from precursor mixtures of tetraethoxysilane and aminopropyltriethoxysilane in ethanol/water solutions via a novel one-pot sol-gel procedure. [ABSTRACT FROM AUTHOR]

In this work, to elevate weak osteoconductivity of titanium (Ti) implant, we prepared a Ti implant having both calcium and phosphate ions on its surface. To modify calcium and phosphate ions onto Ti, phosphate ions were first immobilized by treating the Ti with a NaH 2 PO 4 solution, followed by CaCl 2 treatment to immobilize calcium ions, which created the calcium and phosphate ions-modified Ti (Ca-P-Ti). X-ray photoelectron spectroscopy and thin-layer X-ray diffraction measurement confirmed that both phosphate and calcium ions were co-immobilized onto the Ti surface on the molecular level. Three-hour after seeding MC3T3-E1 murine pre-osteoblast cells on substrates, cell number on Ca-P-Ti was much larger than that of Ti and phosphate-modified Ti (P-Ti), but was similar to that of calcium-modified Ti (Ca-Ti). Also, MC3T3-E1 cells on Ca-P-Ti expressed larger amount of vinculin, a focal adhesion protein, than those on other substrates, probably resulting in larger cell size as well as greater cell proliferation on Ca-P-Ti than those on other substrates. Alkaline phosphatase activity of cells on Ca-P-Ti was greater than those on Ti and P-Ti, but was almost comparable to that of Ca-Ti. Moreover, the largest amount of bone-like nodule formation was observed on Ca-P-Ti. These results provide evidence that calcium and phosphate ions-co-immobilization onto Ti increased the osteoconductivity of Ti by stimulating the responses of pre-osteoblast cells. This simple modification would be promising technique for bone tissue implant including dental and orthopedic implants. [ABSTRACT FROM AUTHOR]

Porous calcium carbonate (CaCO 3 ) has attracted attention as an artificial bone substitute. We previously reported that interconnected porous calcite block can be fabricated when calcite granules are exposed to acidic calcium phosphate (ACaP) under loading conditions. Dicalcium phosphate dihydrate (DCPD) formed on the surface of the calcite granules caused bridging of the calcite granules with one another and formed an interconnected porous calcite block with DCPD. In this study, the effect of the ACaP concentration on the mechanical strength of the interconnected porous calcite was studied under loading conditions. When the ACaP concentration was increased, the amount of DCPD increased and the compressive strength of the porous calcite increased to approximately 2 MPa. The interconnected porous structure was maintained regardless of the ACaP concentration. No statistically significant difference was observed for the porosity, which was approximately 50%, based on the concentration of ACaP. Therefore, we concluded that the amount of precipitated DCPD can be regulated by the concentration of ACaP solution, and the mechanical strength of the porous calcite can be regulated by the amount of the precipitated DCPD. [ABSTRACT FROM AUTHOR]

Apatite cement (AC), which has excellent osteoconductive ability, and alpha-tricalcium phosphate (α-TCP), which can be used for bone replacement, are useful bone substitute materials. The objective of this study was to clarify the physical properties and antimicrobial release ability of antibiotic-loaded AC/α-TCP composites in vitro. Gentamicin-loaded, rapid setting AC/α-TCP composites were prepared in 2 mixing ratios (10:3 and 10:6). The cement paste of AC/α-TCP composites was prepared in a plastic mold and dried in a thermostatic chamber at 37 °C and 100% relative humidity for 24 h. A diametral tensile strength test, powder X-ray diffraction analysis, and gentamicin release test were performed. The diametral tensile strengths of the AC/α-TCP composites were significantly less than that of AC alone. Powder X-ray diffraction patterns exhibited the characteristic peaks of hydroxyapatite in the AC/α-TCP composites and gentamicin-loaded AC/α-TCP composites. The concentration of the released gentamicin was maintained above the minimum inhibitory concentration of Staphylococcus aureus until Day 30 in both the gentamicin-loaded AC/α-TCP composites (10:3 and 10:6). Our results suggest that a gentamicin-loaded AC/α-TCP composite has potential as a drug delivery system. Further study is essential to investigate the antimicrobial activity and safety of the gentamicin-loaded AC/α-TCP composites in animal models. [ABSTRACT FROM AUTHOR]

Interconnected macroporous calcium phosphate has attracted attention as an artificial bone substitute as well as a scaffold for tissue engineering. In this investigation, a setting reaction between α-tricalcium phosphate (α-TCP) spheres and an acidic calcium phosphate solution (0.2 mol/L monocalcium phosphate monohydrate – 0.1 mol/L phosphoric acid) was studied to assess the feasibility of fabricating fully interconnected macroporous calcium phosphate. When 1.3 mm-diameter α-TCP spheres were exposed to an acidic calcium phosphate solution, brushite (dicalcium phosphate dihydrate) was formed on the surface of the α-TCP spheres. The precipitated brushite crystals interlocked with one another and bridged the α-TCP spheres, resulting in a 10 min setting reaction at 37 °C that produced fully interconnected macroporous calcium phosphate. The resultant calcium phosphate macroporous structure had a porosity of 49.7±2.5% and an average pore size of 312±160 μm. [ABSTRACT FROM AUTHOR]

Abstract: 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 110μm for the hybrids frozen at −20°C, and about 50μm 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. [Copyright &y& Elsevier]

Abstract: In the brain after infarction or trauma, the tissue eventually becomes pannecrotic and forms a cavity. In such situations, a scaffold is necessary for the implanted or migrated cells to produce new tissue. In this present study, therefore, we attempted to restore brain tissue using a novel biomaterial, polydimethylsiloxane–tetraethoxysilane (PDMS-TEOS) hybrid with or without vascular endothelial growth factor (VEGF), which is crucial for new vessel formation. When PDMS-TEOS scaffold was implanted into the artificial brain defect, it remained at the implanted site and kept the integrity of the brain shape. At 30 days after the implantation, the marginal territory of PDMS-TEOS scaffold became occupied by newly formed tissue. Immunohistochemical analysis revealed that the new tissue was constituted by astrocytes and endothelial cells. Addition of VEGF increased the newly produced tissue volume, and the immunohistochemical analysis showed that the numbers of astrocytes and endothelial cells were increased. Double staining with proliferation maker Ki67 demonstrated that VEGF significantly increased newly formed astrocytes and endothelial cells, indicating that addition of VEGF accelerated tissue restoration and angiogenesis. These findings show that implantation of PDMS-TEOS scaffold with VEGF might be effective for treating old brain infarction or trauma. [Copyright &y& Elsevier]

Beta-tricalcium phosphate (βTCP) granules are commonly used as an artificial bone graft material. Meanwhile, the surface morphology of the bone graft is an important factor for cellular response. In this study, feasibility study on surface morphology regulation of βTCP bone graft for enhancing cellular response were investigated. The regulation was achieved on the basis of a multistep heating process. Briefly, initial heat treatment of βTCP granules at 1300 °C for 12 h resulted in fabrication of alpha-tricalcium phosphate (αTCP) granules with interconnected micropores. In the second heat treatment, exposure of αTCP granules to 100% relative humidity at 100 °C resulted in partial hydrolysis of αTCP, leading to the fabrication of needle-like calcium-deficient hydroxyapatite (cdHAp) crystals on the αTCP surface. After the third heat treatment at 1100 °C, both cdHAp and αTCP converted back to βTCP, and interconnected micropores with a roughened surface structure were formed. In vitro cell evaluation demonstrated that βTCP granules obtained by the series of heat treatments exhibited 24 times higher cell proliferation at day 9, and four times higher alkaline phosphatase activity compared with untreated βTCP granules. Therefore, we concluded that regulation of surface morphology by a series of heat treatments is useful for improving cellular response to βTCP bone grafting materials. [ABSTRACT FROM AUTHOR]

An amorphous titania gel layer was formed on the titanium surface after the titanium specimen was treated with a H2O2/0.1 m HCl solution at 80°C. The thickness of the gel layer increased almost linearly with the period of the treatment. A subsequent heat treatment above 300°C transformed gradually the amorphous gel to the anatase crystal structure and the rutile started to appear after heat treatment at 600°C. Meanwhile, the densification of the gel occurred significantly after heat treatment above 700°C. Similar to the sol–gel derived titania gel coatings, titania gel layers obtained in the present study exhibited in vitro apatite deposition ability after the gel layers exceeded a minimum thickness (0.2 μm) and was subsequently heated in a proper temperature range (400–600°C). [Copyright &y& Elsevier]

Anatase films with sub-micron porous structure were deposited homogeneously on Ti substrates by simply soaking in 15 wt.% hydrogen peroxide solution at 80 °C for 1 h followed by heating at 300 °C for 1 h in air. Deposition of the porous titania film was not sensitive to substrate morphology, whilst affected readily by the reaction rate. [Copyright &y& Elsevier]

• Ozone treatment removed hydrocarbon contaminants and introduced –OH groups on acid-etched titanium. • Surface hydrophilicity of acid-etched titanium was significantly higher after ozone treatment. • Ozone-treated titanium promoted mesenchymal stem cell proliferation and osteogenic differentiation. • Ozone gas treatment has potential to improve osteoconductivity of titanium implants. Surface wettability is attracting increasing attention as an important factor that affects the cell/tissue responses of implant materials. Time-dependent hydrocarbon adsorption on the titanium (Ti) implant surface has been reported to decrease the surface hydrophilicity by adsorption of hydrocarbon contaminants from the atmosphere and dramatically decrease the osseointegration over time. In this study, we found that ozone-gas-mediated removal of hydrocarbon contaminants and introduction of –OH groups significantly increased the surface hydrophilicity of acid-etched Ti without changing the original surface topography. Ozone-gas-treated Ti dramatically enhanced osteogenic differentiation of mesenchymal stem cells, as evidenced by greater cell proliferation, alkaline phosphatase activity, and bone-like nodule formation compared with original Ti. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Phosphate-modified PEEK is successfully prepared. • Phosphate-modified PEEK enhances bone marrow stromal cells responses. • Phosphate-modified PEEK mitigates inflammatory responses by macrophage. • Phosphate modification can significantly improve implant-bone bonding strength in vivo. Abstract Poly(ether ether ketone) (PEEK) has emerged as an alternative endosseous material to metal implants mainly because of its lack of allergic sensitivity and radiolucency, while maintaining similar mechanical properties with bone. However, a disadvantage of PEEK is its weak osseointegration ability compared with metal implants. To overcome this, we prepared a phosphate group-modified PEEK by plasma treatment and subsequent phosphorylation reaction. Plasma treatment and phosphate modification of PEEK changed its hydrophobic surface to a hydrophilic surface while maintaining the original surface topography and roughness. Phosphate modification increased the bioactivity of rat bone marrow stromal cells (BMSCs), including proliferation, alkaline phosphatase activity, and bone-like nodule formation; however, this effect was negligible in plasma-treated PEEK. In addition, phosphate modification attenuated the phenotypic polarization of lipopolysaccharide-primed RAW264.7 macrophages to an inflammatory phenotype, based on the finding that macrophages on phosphate-modified PEEK produced decreased levels of the inflammatory cytokine and increased levels of the anti-inflammatory cytokine. Finally, in an animal study, phosphate-modified PEEK exhibited a doubled pullout force from the femur bone cavity compared with bare PEEK. Thus, we conclude that phosphate modification can significantly improves the implant-bone bonding strength of PEEK by enhancing BMSCs activity and reducing excessive inflammation. [ABSTRACT FROM AUTHOR]

Although sintered β-tricalcium phosphate blocks have been used clinically as artificial bone substitutes, the crystallinity of β-tricalcium phosphate, which might dominate biocompatibility, is extremely high. The objective of this study is to evaluate the feasibility of fabricating low-crystallinity β-tricalcium phosphate blocks, which are expected to exhibit good biocompatibility via a dissolution–precipitation reaction of α-tricalcium phosphate blocks as a precursor under hydrothermal conditions at 200°C for 24 h. Although β-tricalcium phosphate is a metastable phase, the presence of Mg2+ in the reaction solution inhibits the formation of its corresponding stable phase and induces β-tricalcium phosphate formation under acidic conditions. It was found that low-crystallinity β-tricalcium phosphate blocks could be fabricated from α-tricalcium phosphate blocks immersed in 1.0 mol/L MgCl2 + 0.1 mol/L NaH2PO4 solution while maintaining the shape of the α-tricalcium phosphate blocks. The crystallite size of the fabricated β-tricalcium phosphate blocks was 42 nm, which was substantially smaller than that of the sintered β-tricalcium phosphate blocks. When the fabricated β-tricalcium phosphate blocks were implanted into bone defects in rabbit femurs, they exhibited excellent tissue responses. In particular, the initial osteoconductivity (two and four weeks) was substantially greater than that of sintered β-tricalcium phosphate blocks. [ABSTRACT FROM AUTHOR]

Dental implants made of pure titanium suffer from abrasion and scratch during routine oral hygiene procedures. This results in an irreversible surface damage, facilitates bacteria adhesion and increases risk of peri-implantitis. To overcome these problems, titanium nitride (TiN) coating was introduced to increase surface hardness of pure titanium. However, the osteoconductivity of TiN is considered to be similar or superior to that of titanium and its alloys and therefore surface modification is necessary. In this study, TiN coating prepared through gas nitriding was partially oxidized by hydrothermal (HT) treatment and ozone (O 3 ) treatment in pure water to improve its osteoconductivity. The effects of HT treatment and O 3 treatment on surface properties of TiN were investigated and the osteoconductivity after undergoing treatment was assessed in vitro using osteoblast evaluation. The results showed that the critical temperature for HT treatment was 100 °C since higher temperatures would impair the hardness of TiN coating. By contrast, O 3 treatment was more effective in oxidizing TiN surfaces, improving its wettability while preserving its morphology and hardness. Osteoblast attachment, proliferation, alkaline phosphatase (ALP) expression and mineralization were improved on oxidized specimens, especially on O 3 treated specimens, compared with untreated ones. These effects seemed to be consequences of partial oxidation, as well as improved hydrophilicity and surface decontamination. Finally, it was concluded that, partially oxidized TiN is a promising coating to be used for dental implant. [ABSTRACT FROM AUTHOR]

Abstract: Much interest has recently been shown in the potential utility of bioartificial liver (BAL) as a bridge support for patients and as a module for experimental purposes. A radial-flow bioreactor (RFB), one of the perfused bed/scaffold-type bioreactors, enables a highly functional three-dimensional culture as BAL. The functional capacity of bioreactors depends not only on their mechanistic structures but also on scaffolds packed in them. In the present study, we examined the possible utility of a new porous organic–inorganic-hybrid scaffold in an RFB. The scaffold was made from tetraethoxysilane (TEOS) and polydimethylsiloxane (PDMS) by a sol–gel method using sieved sucrose particles as a porogen. In the porous TEOS–PDMS hybrid scaffold, human hepatocellular carcinoma cells (HepG2) proliferated actively and formed cell clusters more efficiently than they did in a polyvinyl-alcohol scaffold. When cultivated in PDMS–TEOS, HepG2 cells secreted a ∼three-fold greater amount of albumin than that secreted in a monolayer culture. For potential application of BAL to pharmacological studies and future clinical use, it is essential to develop a method to propagate liver cells that maintain highly specific functions. The present results indicate that PDMS–TEOS may be a promising scaffold for developing such functional culture methods. [Copyright &y& Elsevier]

Amelogenesis consists of secretory, transition, maturation, and post-maturation stages, and the morphological changes of ameloblasts at each stage are closely related to their function. p130 Crk-associated substrate (Cas) is a scaffold protein that modulates essential cellular processes, including cell adhesion, cytoskeletal changes, and polarization. The expression of p130Cas was observed from the secretory stage to the maturation stage in ameloblasts. Epithelial cell-specific p130Cas-deficient (p130Cas Δepi- ) mice exhibited enamel hypomineralization with chalk-like white mandibular incisors in young mice and attrition in aged mouse molars. A micro-computed tomography analysis and Vickers micro-hardness testing showed thinner enamel, lower enamel mineral density and hardness in p130Cas Δepi- mice in comparison to p130Cas flox/flox mice. Scanning electron microscopy, and an energy dispersive X-ray spectroscopy analysis indicated the disturbance of the enamel rod structure and lower Ca and P contents in p130Cas Δepi- mice, respectively. The disorganized arrangement of ameloblasts, especially in the maturation stage, was observed in p130Cas Δepi- mice. Furthermore, expression levels of enamel matrix proteins, such as amelogenin and ameloblastin in the secretory stage, and functional markers, such as alkaline phosphatase and iron accumulation, and Na+/Ca2++K+-exchanger in the maturation stage were reduced in p130Cas Δepi- mice. These findings suggest that p130Cas plays important roles in amelogenesis (197 words). [Display omitted] • We examined the physiological role of p130Cas on amelogenesis using epithelial cell-specific p130Cas-deficient (p130Cas Δepi -) mice in vivo. • p130Cas Δepi- mice exhibited enamel hypomineralization with chalk-like white incisors in young mice and attrition in aged mouse molars. • Disorganized arrangement of ameloblasts were observed especially in the mature stage of p130Cas Δepi- mice. • Amelogenin and ameloblastin in the secretory stage, and alkaline phosphatase, iron accumulation, and Na+/Ca2++K+-exchanger in the maturation stage were reduced in ameloblasts from p130Cas Δepi- mice. • Our findings suggest that p130Cas plays important roles in amelogenesis. [ABSTRACT FROM AUTHOR]

• Phosphate and Ca (PCa) modified Ti-6Al-4V stimulate preosteoblast proliferation. • PCa modification promotes osteogenic differentiation of preosteoblasts. • PCa functionalization enhances osseointegration activity of Ti-6Al-4V in vivo. This study aimed to determine the bioactivities and osseointegration activities of Ti-6Al-4V after surface functionalization with a combination of phosphate and calcium. Several Ti-6Al-4V containing different amounts of phosphate and/or calcium on their surface were prepared. Phosphate was introduced by allowing samples to react with H 3 PO 4 , and the resulting phosphate-modified samples were further allowed to react with CaCl 2 to obtain phosphate- and calcium-co-immobilized samples. Cell studies revealed that the co-immobilization of phosphate and calcium significantly promoted MC3T3-E1 preosteoblast proliferation and osteogenic differentiation, compared to that in unmodified, phosphate-modified, or calcium-modified Ti-6Al-4V. Furthermore, after implants were inserted into the bone marrow cavity of a rat femur, the osseointegration activity and bond strength between implants and the bone were increased in a phosphate- and calcium-functionalized sample, compared to those in a bare sample. [ABSTRACT FROM AUTHOR]

The material concept of resin cements capable of disintegrating due to near-infrared (NIR) radiation was verified. The cements were prepared by adding silicon carbide (SiC), which heats upon absorbing NIR rays, and thermally expandable particles (TEPs) to 4-META/MMA-TBB resin cement. The microtensile bond strength (µTBS) and cytocompatibility of the cements were evaluated. The resin cements with 5 mass% SiC and 20-40 mass% TEPs had significantly lower µTBS after NIR radiation than before NIR radiation, and their cytocompatibility was not decreased by SiC and TEPs additions. Furthermore, in vitro thermal damage tests were performed using the resin cement with 5 mass% SiC and 20 mass% TEPs, a typical composition. The results demonstrated conditions that significantly reduced µTBS and minimized thermal damage by NIR radiation. Although these data are only proof of concept, the possibility that dental devices bonded with these cements could be detached by NIR radiation was demonstrated.

We have previously reported that a novel bioresorbable self-setting injectable bone paste composed of hydroxyapatite/collagen bone-like nanocomposite (HAp/Col) and (3-glycidoxypropyl)trimethoxysilane (GPTMS) was successfully prepared and was replaced with new bone within 3 months of implantation in defects created in porcine tibia. In this study, the HAp/Col-GPTMS paste was implanted into bone defects in rat tibiae to investigate the initial kinetics and bone tissue response. Even though more than 35% of GPTMS molecules should be eluted rapidly from directly injected pastes according to previously reported cell culture tests, in this study, energy-dispersive X-ray spectrometry did not detect Si (GPTMS) deposition in tissues surrounding the paste at 1 day postimplantation. Further, no abnormal inflammatory responses were observed in the surrounding tissues over the test period for both directly injected and prehardened pastes. Companying these observations with the results of the previous animal test (in which the paste was fully resorbed and was substituted with new bone), the eluted GPTMS resolved in no harm in vivo from the initial to final (completely resorbed) stages. Material resorption rates calculated from X-ray microcomputed tomography (μ-CT) images decreased with increasing in GPTMS concentration. Histological observations indicated that tartrate-resistant acid phosphatase (TRAP) active cells, (assumed to be osteoclasts), exist on the periphery of pastes. This result suggested that the paste was resorbed by osteoclasts in the same way as the HAp/Col. Since a good correlation was observed between TRAP active areas in histological sections and material resorption rate calculated from μ-CT, the TRAP activity coverage ratio offers the possibility to estimate the osteoclastic resorption ratio of materials, which are replaced with bone via bone remodeling process., (© 2024 The Author(s). Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.)

To improve the cytocompatibility of mineral trioxide aggregate (MTA) cement and its ability for reparative dentin formation, the effect of adding choline dihydrogen phosphate (CDHP), which is reported to be biocompatible, to MTA cement was investigated. The L929 cell proliferation showed that the addition of CDHP improved cell viability. The addition of CDHP shortened the setting time of MTA cement, with a significant decrease in consistency above 0.4 g/mL. Diametral tensile strength of the set cement was improved by the addition of 0.4 g/mL CDHP. Solubility was judged to be within the range of clinical application. The spontaneous precipitation of low crystalline hydroxyapatite was examined by immersing the set cement in phosphate buffer saline, and it was found that the ability of the cement with 0.4 g/mL of CDHP was significantly improved compared with that of the cement without CDHP.

We prepared hydroxyapatite (HAp) bone grafts by the setting reaction of calcium phosphate cement, and investigated the effects of the porosity and crystallinity on the osteoconductivity and bioresorbability. We examined the effect of the water-mixing ratio, pressure, and post-heat treatment temperature during preparation on the crystallite size and porosity of the HAp blocks. The quantity of protein adsorption increased with increasing porosity and specific surface area (SSA) of the HAp blocks, whereas the initial cell attachment was similar despite the different porosities and crystallinities. In in vitro dissolution tests with a pH 5.5 buffer, which mimics an osteoclast-created Howship's lacuna, both the porosity and SSA of the HAp blocks affected the solubility; most likely due to the increased contact area with the buffer. Thus, HAp blocks prepared by the setting reaction of calcium phosphate cement could be applicable for bioresorbable HAp bone grafts because of the high porosity and SSA.

The purpose of this study was to evaluate the surface modification of calcium ions on roughened titanium as a surface treatment of dental implants for cell attachment, growth, and initial bacterial adhesion. When a surface-roughened, pure titanium disk was immersed in a calcium chloride solution (100 mM) containing 20 ppm ozone for 24 h at 25ºC, calcium was detected on the surface by X-ray photoelectron spectroscopy. The calcium-modified, roughened titanium disk had a significantly greater concentration of the initially adhered cells as well as cells cultured over 7 days compared with titanium disks without surface modification. Furthermore, the initial bacterial adhesion on the calcium-ozone treated titanium disk was statistically less than on a pure titanium disk or titanium disk treated without ozone. Dissolved ozone was useful for modifying the surface of roughened titanium with calcium ions and the surface modification may be applicable for dental implants.

Carbonate apatite (CO 3 Ap) granules are known to show good osteoconductivity and replaced to new bone. On the other hand, it is well known that a porous structure allows bone tissue to penetrate its pores, and the optimal pore size for bone ingrowth is dependent on the composition and structure of the scaffold material. Therefore, the aim of this study was to fabricate various porous CO 3 Ap granules through a two-step dissolution-precipitation reaction using CaSO 4 as a precursor and 30-, 50-, 120-, and 205-μm diameter microfibers as porogen and to find the optimal pore size of CO 3 Ap. Porous CO 3 Ap granules were successfully fabricated with pore size 8.2-18.7% smaller than the size of the original fiber porogen. Two weeks after the reconstruction of rabbit calvarial bone defects using porous CO 3 Ap granules, the largest amount of mature bone was seen to be formed inside the pores of CO 3 Ap (120) [porous CO 3 Ap granules made using 120-μm microfiber] followed by CO 3 Ap (50) and CO 3 Ap (30). At 4 and 8 weeks, no statistically significant difference was observed based on the pore size, even though largest amount of mature bone was formed in case of CO 3 Ap (120). It is concluded, therefore, that the optimal pore size of the CO 3 Ap is that of CO 3 Ap (120), which is 85 μm., (© 2019 Wiley Periodicals, Inc.)

Two types of synthetic carbonate apatite [potassium-containing carbonate apatite (CAK) and sodium-containing carbonate apatite (CANa)] were prepared and characterized by thermogravimetric analysis, X-ray diffraction analysis (XRD) and Fourier transform infrared spectroscopy. The chemical formulas of carbonate apatite were determined to be Ca 9.36 K 0.12 (PO 4 ) 5.12 (CO 3 ) 0.88 (OH) 1.73 and Ca 8.72 Na 1.33 (PO 4 ) 4.96 (CO 3 ) 1.04 (OH) 1.80 , respectively. Thermogravimetric analysis showed that the final weight loss at 1,200°C reached about 11.2% for CAK and 13.9% for CANa. Carbonate loss gradually occurred above 150°C and continued to 1,200°C. The crystallinity of the apatite phase was found to be much improved between 800 and 850°C for CAK and 750 and 800°C for CANa, where rapid carbonate loss occurred. A small amount of CaO formed above 900°C. For CANa, NaCaPO 4 also formed above 700°C in both apatites. Although the lattice parameters of the carbonate apatites varied with temperature, the final a and c lattice parameters attained constant values of 0.9421 and 0.6881 nm.

Carbonate apatite (CO 3 Ap) block can be used as a bone substitute because it can be remodeled to new natural bone in a manner conforming with the bone remodeling process. Among the many porous structures available, honeycomb (HC) structure is advantageous for rapid replacement of CO 3 Ap to bone. In this study, the feasibility to fabricate a CO 3 Ap HC was studied, along with its initial tissue response in rabbit femur bone defect. First, a mixture of Ca(OH) 2 and a wax-based binder was extruded from a HC mold. Then the fabricated HC was heated for binder removal and carbonation at 450°C in a mixed O 2 -CO 2 atmosphere, forming a CaCO 3 HC. When the CaCO 3 HC was immersed in 1 mol/L Na 3 PO 4 solution at 80°C for 7 days, its composition changed from CaCO 3 to CO 3 Ap, maintaining the structure of the original CaCO 3 HC. Compressive strengths of the CaCO 3 and CO 3 Ap HCs were 65.2 ± 7.4 MPa and 88.7 ± 4.7 MPa, respectively. When the rabbit femur bone defect was reconstructed with the CO 3 Ap HC, new bone penetrated the CO 3 Ap HC completely. Osteoclasts and osteoblasts were found on the surface of the newly formed bone and osteocytes were also found in the newly formed bone, indicating ongoing bone remodeling. Furthermore, blood vessels were formed inside the pores of CO 3 Ap HC. Therefore, CO 3 Ap HC has good potential as an ideal bone substitute. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1014-1020, 2019., (© 2019 Wiley Periodicals, Inc.)

Objectives: The aim of this present study was to investigate the effect of setting atmosphere on replacement of apatite cement with new bone both in vitro and in vivo., Material and Methods: Apatite cement consisting of an equimolar mixture of tetracalcium phosphate and anhydrous dicalcium phosphate was mixed with distilled water and allowed to set at 37 °C and 100% relative humidity under 0% , 5%, and 100% CO 2 atmospheres. X-Ray diffraction and Fourier Transform Infrared Spectroscopy were employed to confirm the carbonate apatite formation. Micro-CT and histological evaluation was made at 1 and 6 month(s) using twelve 10-week-old specific-pathogen-free male Wistar rats., Results: B-type carbonate apatite was found when the apatite cement was set under 100% CO 2 and 5% CO 2 . More carbonate apatite was formed in the case of 100% CO 2 when compared with 5% CO 2 , and none was formed under 0% CO 2 . Interestingly, unreacted tetracalcium phosphate was significant when apatite cement was set under 0% CO 2 , indicating the formation of Ca-deficient hydroxyapatite. When a bone defect of rat tibia was reconstructed in these conditions of apatite cement and sintered hydroxyapatite, replacement of the apatite cement was confirmed 6 months after implantation, whereas no replacement was observed in the case of sintered hydroxyapatite. The amount of replacement of apatite cement with bone was greater, on the order of 100% CO 2 and 5% CO 2 , followed by 0% CO 2 ., Conclusion: The results obtained in the present study demonstrated that setting atmosphere clearly plays an important role in the replacement of set apatite cement with bone., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Carbonate apatite-coated calcium carbonate (CO 3 Ap/CaCO 3 ) was fabricated through a dissolution-precipitation reaction using CaCO 3 granules as a precursor to accelerate bone replacement based on superior osteoconductivity of the CO 3 Ap shell, along with Ca 2+ release from the CaCO 3 core and quicker resorption of the CaCO 3 core. In the present study, CaCO 3 , 10% CO 3 Ap/CaCO 3 , 30% CO 3 Ap/CaCO 3 , and CO 3 Ap granules were fabricated and examined histologically to evaluate their potential as bone substitutes. Larger contents of CaCO 3 in the granules resulted in higher Ca 2+ release and promoted cell proliferation of murine preosteoblasts at 6 days compared with CO 3 Ap. Interestingly, in a rabbit femur defect model, 10% CO 3 Ap/CaCO 3 induced significantly higher new bone formation and higher material resorption compared with CO 3 Ap at 8 weeks. Nevertheless, CO 3 Ap showed a superior osteoconductive potential compared with 10% CO 3 Ap/CaCO 3 at 8 weeks. All tested granules were most likely resorbed by cell mediation including multinucleated giant cell functions. Therefore, we conclude that CO 3 Ap/CaCO 3 has a positive potential for bone tissue engineering based on well-controlled calcium release, bone formation, and material resorption., (© 2018 John Wiley & Sons, Ltd.)

Although β-tricalcium phosphate (β-TCP) is widely used in clinical applications as a bone substitute owing to its positive tissue response and its ability to be replaced by new bone through a bone-remodeling process, it has the limitation of rapid resorption in vivo, which might become a reason for tissue atrophy and high crystallinity, which decrease biocompatibility. A reduction in the crystallinity might increase the biocompatibility of the bone substitute. To overcome the drawbacks of β-TCP, decrease in crystallinity and solubility, both are required. Therefore, in this study, the feasibility of fabricating Mg substituted low crystalline β-TCP (Mg-LC-β-TCP) granules formed in aqueous solution was evaluated in vivo focusing long-term adsorption and bone formation in bone defects formed in the rabbit femur using sintered β-TCP granules as a control. With Mg-LC-β-TCP, the resorption of the substitute was suppressed, and no tissue atrophy was observed even at 24 weeks post-implantation, whereas a few granules with surrounding tissue atrophy were observed at 12 weeks post-implantation. Tartrate-resistant acid phosphatase-staining indicated that the density of osteoclasts type cells with Mg-LC-β-TCP was significantly lower than that with β-TCP, and also the numbers of osteoblasts type cells with Mg-LC-β-TCP were significantly higher than that with β-TCP. It is suggested that Mg substitution to form low crystallinity β-TCP is a valuable way to overcome the limitations of β-TCP as a bone substitute.

Carbonate apatite (CO 3 Ap) is an inorganic component of bone. This study aimed to compare the composition and tissue response to of CO 3 Ap (CO 3 Ap-DP) fabricated by the dissolution-precipitation reaction using calcite as a precursor and Bio-Oss®, which is widely used in orthopedic and dental fields as a synthetic bone substitute. X-ray diffraction and Fourier transform infrared results showed that CO 3 Ap-DP and Bio-Oss® were both B-type carbonate apatite with low crystallinity. The average sizes of CO 3 Ap-DP and Bio-Oss® granules were 450 ± 58 and 667 ± 168μ m, respectively, and their carbonate contents were 12.1 ± 0.6 and 5.6 ± 0.1 wt%, respectively. CO 3 Ap-DP had a larger amount of CO 3 than Bio-Oss® but higher crystallinity than Bio-Oss®. When a bone defect made at the femur of rabbits was reconstructed with CO 3 Ap-DP and Bio-Oss®, CO 3 Ap-DP granules were partially replaced with bone, whereas Bio-Oss® remained at 8 weeks after implantation. CO 3 Ap-DP granules elicited a significantly larger amount of new bone formation at the cortical bone portion than Bio-Oss® at 4 weeks after the implantation. The results obtained in the present study demonstrated that CO 3 Ap-DP and Bio-Oss® showed different behavior even though they were both classified as CO 3 Ap. The CO 3 content in CO 3 Ap played a more important role than the crystallinity of CO 3 Ap for replacement to bone and high osteoconductivity.

β-Tricalcium phosphate [β-TCP] is the typical bone substitute due to its excellent osteoconductivity and bioresorbability. One of the keys to improve its potential as bone substitute is to introduce porous structure and its regulation. In this study, interconnected porous β-TCP blocks were fabricated through a setting reaction of β-TCP granules and subsequent heat treatment. First, β-TCP granules were mixed with HNO 3 . Upon mixing, β-TCP granules were bridged with dicalcium phosphate dihydrate [DCPD: CaHPO 4 ·2H 2 O] containing Ca(NO 3 ) 2 . Then, the DCPD-bridged β-TCP was heated at 1100°C. During the heating process, DCPD containing Ca(NO 3 ) 2 transformed into β-TCP and bonded with β-TCP granules. As a result, an interconnected porous β-TCP block formed. The diametral tensile strength and porosity of the interconnected porous β-TCP block fabricated from 200-300-μm β-TCP granules and 5 N HNO 3 and then heated at 1,100°C were 1.4 ± 0.2 MPa and 57% ± 2%, respectively. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 797-804, 2018., (© 2017 Wiley Periodicals, Inc.)

Carbonate apatite (CO 3 Ap) foam with an interconnected porous structure is highly attractive as a scaffold for bone replacement. In this study, arbitrarily shaped CO 3 Ap foam was formed from α-tricalcium phosphate (α-TCP) foam granules via a two-step process involving treatment with acidic calcium phosphate solution followed by hydrothermal treatment with NaHCO 3 . The treatment with acidic calcium phosphate solution, which is key to fabricating arbitrarily shaped CO 3 Ap foam, enables dicalcium hydrogen phosphate dihydrate (DCPD) crystals to form on the α-TCP foam granules. The generated DCPD crystals cause the α-TCP granules to interlock with each other, inducing an α-TCP/DCPD foam. The interlocking structure containing DCPD crystals can survive hydrothermal treatment with NaHCO 3 . The arbitrarily shaped CO 3 Ap foam was fabricated from the α-TCP/DCPD foam via hydrothermal treatment at 200 °C for 24 h in the presence of a large amount of NaHCO 3 .

β-Tricalcium phosphate (β-TCP) has attracted much attention as an artificial bone substitute owing to its biocompatibility and osteoconductivity. In this study, osteoconductivity of β-TCP bone substitute was enhanced without using growth factors or cells. Dicalcium phosphate dihydrate (DCPD), which is known to possess the highest solubility among calcium phosphates, was coated on β-TCP granules by exposing their surface with acidic calcium phosphate solution. The amount of coated DCPD was regulated by changing the reaction time between β-TCP granules and acidic calcium phosphate solution. Histomorphometry analysis obtained from histological results revealed that the approximately 10mol% DCPD-coated β-TCP granules showed the largest new bone formation compared to DCPD-free β-TCP granules, approximately 2.5mol% DCPD-coated β-TCP granules, or approximately 27mol% DCPD-coated β-TCP granules after 2 and 4weeks of implantation. Based on this finding, we demonstrate that the osteoconductivity of β-TCP granules could be improved by coating their surface with an appropriate amount of DCPD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study aimed to evaluate in vivo behavior of a carbonate apatite (CO 3 Ap) block fabricated by compositional transformation via a dissolution-precipitation reaction using a calcium hydrogen phosphate dihydrate [DCPD: CaHPO 4 ·2H 2 O] block as a precursor. These blocks were used to reconstruct defects in the femur and tibia of rabbits, using sintered dense hydroxyapatite (HAp) blocks as the control. Both the CO 3 Ap and HAp blocks showed excellent tissue response and good osteoconductivity. HAp block maintained its structure even after 24 weeks of implantation, so no bone replacement of the implant was observed throughout the post-implantation period in either femoral or tibial bone defects. In contrast, CO 3 Ap was resorbed with increasing time after implantation and replaced with new bone. The CO 3 Ap block was resorbed approximately twice as fast at the metaphysis of the proximal tibia than at the epiphysis of the distal femur. The CO 3 Ap block was resorbed at an approximately linear change over time, with complete resorption was estimated by extrapolation of data at approximately 1-1.5 years. Hence, the CO 3 Ap block fabricated in this study has potential value as an ideal artificial bone substitute because of its resorption and subsequent replacement by bone.

Bone-forming cells and Mϕ play key roles in bone tissue repair. In this study, we prepared a superhydrophilic titanium implant functionalized by ozone gas to modulate osteoconductivity and inhibit inflammatory response towards titanium implants. After 24 h of ozone gas treatment, the water contact angle of the titanium surface became zero. XPS analysis revealed that hydroxyl groups were greatly increased, but carbon contaminants were largely decreased 24 h after ozone gas functionalization. Also, ozone gas functionalization did not alter titanium surface topography. Superhydrophilic titanium (O3-Ti) largely increased the aspect ratio, size and perimeter of cells when compared with untreated titanium (unTi). In addition, O3-Ti facilitated rat bone marrow derived MSCs differentiation and mineralization evidenced by greater ALP activity and bone-like nodule formation. Interestingly, O3-Ti did not affect RAW264.7 Mϕ proliferation. However, naive RAW264.7 Mϕ cultured on unTi produced a two-fold larger amount of TNFα than that on O3-Ti. Furthermore, O3-Ti greatly mitigated proinflammatory cytokine production, including TNFα and IL-6 from LSP-stimulated RAW264.7 Mϕ. These results demonstrated that a superhydrophilic titanium prepared by simple ozone gas functionalization successfully increased MSCs proliferation and differentiation, and mitigated proinflammatory cytokine production from both naive and LPS-stimulated Mϕ. This superhydrophilic surface would be useful as an endosseous implantable biomaterials and as a biomaterial for implantation into other tissues.

Appropriate setting time is an important parameter that determines the effectiveness of apatite cement (AC) for clinical application, given the issues of crystalline inflammatory response phenomena if AC fails to set. To this end, the present study analyzes the effects of the method of apatite seed crystals addition on the setting reaction of α-tricalcium phosphate (α-TCP) based AC. Two ACs, both consisting of α-TCP and calcium deficient hydroxyapatite (cdHAp), were analyzed in this study. In one AC, cdHAp was added externally to α-TCP and this AC was abbreviated as AC(EA). In the other AC, α-TCP was partially hydrolyzed to form cdHAp on the surface of α-TCP. This AC was referred to as AC(PH). Results indicate a decrease in the setting time of both ACs with the addition of cdHAp. Among them, for the given amount of added cdHAp, AC(PH) showed relatively shorter setting time than AC(EA). Besides, the mechanical strength of the set AC(PH) was also higher than that of set AC(EA). These properties of AC(PH) were attributed to the predominant crystal growth of cdHAp in the vicinity of the α-TCP particle surface. Accordingly, it can be concluded that the partial hydrolysis of α-TCP may be a better approach to add low crystalline cdHAp onto α-TCP based AC.