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Ocean-scale monitoring of pollution is challenging. Seabirds are useful indicators because they travel over a broad foraging range. Nevertheless, this coarse spatial resolution is not fine enough to discriminate pollution in a finer scale. Previous studies have demonstrated that pollution levels are higher in the Sea of Japan and South and East China Seas than the Northen Pacific Ocean. To test these findings in a wide-ranging animal, we tracked streaked shearwaters (Calonectris leucomelas) from four islands in Japan using global positioning system (GPS) and measured persistent organic pollutants (POPs) in the oil of their preen glands. The POPs did not change during 6 to 21 days when birds from Awashima were foraging only in the Sea of Japan, while it increased when they crossed to the Pacific through the Tsugaru Strait and foraged along the eastern coast of Hokkaido where industrial cities occur. These results indicate that POPs in the oil reflect relatively short-term exposure. Concentrations of POPs displayed greater variation among regions. Total polychlorinated biphenyls were highest in birds foraging in a small area of the semiclosed Seto Inland Sea surrounded by urbanized coast, p,p′-dichlorodiphenyltrichloroethane (DDT) was highest in birds foraging in the East China Sea, and total hexachlorocyclohexanes were highest in birds foraging in the Sea of Japan. All were lowest in birds foraging in the Pacific. This distribution of POPs concentration partly agrees with previous findings based on mussels, fish, and seawater and possibly reflects the mobility and emission sources of each type of POP. These results highlight the importance of information on the foraging area of highly mobile top predators to make them more effective monitors of regional marine pollution. [ABSTRACT FROM AUTHOR]

Abstract: DNA-apatite composite layer (D-Ap layer) and DNA-lipid-apatite composite layer (DLp-Ap layer) were prepared on ceramic hydroxyapatite disk and scaffold using supersaturated calcium phosphate solutions supplemented with 0.5–5μg/mL plasmid and 0–10μL/mL lipid transfection reagent FuGENE®. Both in vitro and in vivo studies were carried out using mesenchymal stem cells (MSCs) and two kinds of gene (luciferase and bone morphogenetic protein (BMP)-2) for demonstrating potential application of the gene transfer system using the D-Ap and DLp-Ap layers in bone tissue engineering. In the in vitro study using luciferase gene, the DLp-Ap layers showed 1–2 orders of magnitudes higher gene transfer efficiency to MSCs than the D-Ap layer. In the in vivo study using BMP-2 gene, DLp-Ap layer slightly increased BMP-2 protein concentration than D-Ap layer, thereby enhancing their osteogenic differentiation than D-Ap layer. The present gene transfer system using the DLp-Ap layers, with the advantages of good biocompatibility, bone-bonding ability, and efficacy in in vitro and in vivo gene transfer to MSCs, would be useful in bone tissue engineering. [Copyright &y& Elsevier]

Background: Pin-tract infections are the most common complications of external fixation. To solve the problem, we developed a fibroblast growth factor-2 (FGF-2)-apatite composite layer for coating titanium screws. The purpose of this study was to elucidate the mechanism of the improvement in infection resistance associated with FGF-2-apatite composite layers. Method: We analyzed FGF-2 release from the FGF-2-apatite composite layer and the mitogenic activity of the FGF-2-apatite composite layer. We evaluated time-dependent development of macroscopic pin-tract infection around uncoated titanium control screws (n = 10). Screws coated with the apatite layer (n = 16) and FGF-2-apatite composite layer (n = 16) were percutaneously implanted for 4 weeks in the medial proximal tibia in rabbits. Results: A FGF-2-apatite composite layer coated on the screws led to the retention of the mitogenic activity of FGF-2. FGF-2 was released from the FGF-2-apatite composite layer in vitro for at least 4 days, which corresponds to a period when 30% of pin-tract infections develop macroscopically in the percutaneous implantation of uncoated titanium control screws. The macroscopic infection rate increased with time, reaching a plateau of 80-90% within 12 days. This value remained unchanged until 4 weeks after implantation. The screws coated with an FGF-2-apatite composite layer showed a significantly higher wound healing rate than those coated with an apatite layer (31.25 vs. 6.25%, p < 0.05). The interfacial soft tissue that bonded to the FGF-2-apatite composite layer is a Sharpey's fiber-like tissue, where collagen fibers are inclined at angles from 30 to 40° to the screw surface. The Sharpey's Wber-like tissue is rich in blood vessels and directly bonds to the FGF-2-apatite composite layer via a thin cell monolayer (0.8-1.7 μm thick). Conclusion: It is suggested that the enhanced wound healing associated with the formation of Sharpey's fiber-like tissue triggered by FGF-2 released from the FGF-2-apatite composite layer leads to the reduction in the pin-tract inflammation rate. [ABSTRACT FROM AUTHOR]

Abstract: A cytochrome C (cyt C) and apatite composite layer was formed on a NaOH- and heat-treated titanium substrate (Ti substrate) by immersing the Ti substrate for one day at 25 °C in supersaturated calcium phosphate solutions obtained by mixing infusion fluids. When the initial supersaturation level of the calcium phosphate solution was increased, the total amount of cyt C and apatite deposited on the Ti substrate increased. On the other hand, the cyt C content in the composite layer decreased with an increase in initial supersaturation level. The morphology of the composite layer markedly changed depending on the initial supersaturation level. Therefore, the initial supersaturation level affected the formation of the cyt C and apatite composite layer. It is expected that fibroblast growth factor-2 can be immobilized on NaOH- and heat-treated titanium substrates using the same method. [Copyright &y& Elsevier]

A pulse generator with large amplitude of 160 V and fast rise time of less than 0.4 ns has been built using a coaxial cable as a capacitor. By combining with the anomalous Hall effect technique for a single magnetic nanodot, magnetization response of one Co/Pt nanodot of 400 nm in diameter to the pulse was examined. By applying a pulse field with the maximum amplitude of 740 Oe and the duration of 10 ns, magnetization switching of the dot by the pulse was successfully observed. The pulse amplitude dependence of switching field suggested that the pulse field and the dc bias field could be treated as a simple summation of the both fields in the time scale of 10 ns. All the results of magnetization switching by the pulse field could be explained qualitatively by classical thermal relaxation process. [ABSTRACT FROM AUTHOR]

Abstract: A composite of poly-ε-caprolactone (PCL) loaded with gatifloxacine (GFLX), an antibiotic, and a β-tricalcium phosphate (βTCP) porous ceramic body was prepared by a solvent-free process in which no toxic solvent was used. GFLX mostly retained its bactericidal property after the processing. The composite of GFLX-loaded PCL and βTCP ceramic released GFLX for 4 weeks in Hanks’ balanced solution, and had sustained bactericidal activity against Streptococcus milleri and Bacteroides fragilis for at least 1 week. The composite of the GFLX-loaded PCL and βTCP ceramic was implanted in an osteomyelitis lesion induced by S. milleri and B. fragilis in the rabbit mandible. The osteomyelitis lesion expanded in the mesial–distal direction when no composite was implanted or when the lesion was treated with debridement only. The composite of GFLX-loaded PCL and βTCP showed efficacy in controlling infection at the bone defect formed by debridement, and supported bone tissue reconstruction at the bone defect. Twelve and 50 weeks after the implantation, the inflammation even disappeared. New bone formation was observed on the surface of the composite after 4 weeks. After 50 weeks, ingrowth of bone tissues with vascular channels was observed along the PCL and βTCP interface, which indicated degradation of PCL and/or βTCP ceramic at the ceramic/polymer interface followed by replacement by bone tissues. The GFLX concentrations in the serum and soft tissues were very low. Therefore, the composite of GFLX-loaded PCL and βTCP ceramic would help arrest osteomyelitis when it is used in addition to intravenous antibiotic administration, and help new bone formation and osteoconduction. [Copyright &y& Elsevier]

Abstract: The color 3D profile measurement laser microscope was applied and evaluated for the quantitative analysis of resorption pits made by osteoclasts cultured on biomaterials for the first time. In this study, we measured the exact volume of resorption pits made by osteoclasts cultured on two synthetic biomaterials, TCP (tricalcium phosphate) and ZnTCP (zinc-containing TCP), and compared the resorbing activity of osteoclasts on the two materials. Mature osteoclasts were isolated from rabbit bone marrow and cultured on discs of TCP and ZnTCP for 24 h. The depth and volume of resorption pits was significantly decreased on ZnTCP compared to TCP, although the plane area of the pits differed little between the two materials. These results suggested that Zn ions released from ZnTCP on mature osteoclasts do not contribute to the early phase of the resorption cycle, but mainly affect the later phase. We demonstrated that the depth, volume, and area of resorption pits can be measured reliably by this technique. [Copyright &y& Elsevier]

Abstract: Titanium metal coated with apatite (HA–Ti), albumin−apatite composite (AA–Ti) or laminin−apatite composite (LA–Ti) was prepared by the immersion of NaOH- and heat-treated titanium metal in a calcium phosphate solution, or one supplemented with albumin or laminin. Platelet adhesion to the obtained materials under flow conditions was investigated in real time using a cone- and plate-type viscometer and fluorescence labeled platelets. Adhesion and activation of the platelets on the HA–Ti, AA–Ti and LA–Ti were definitely suppressed as compared with those on untreated titanium metal with a mirror surface. Furthermore, the numbers of platelets adhered to AA−Ti and LA–Ti are smaller than those adhered to HA–Ti, although the differences were not statistically significant. These findings suggest that HA–Ti, AA–Ti and LA–Ti, especially AA–Ti and LA–Ti, would exhibit thromboresistance that is superior to commercially pure titanium metal in terms of platelet adhesion. [Copyright &y& Elsevier]

Abstract: Cytochrome C (cyt C), which has a molecular weight and an isoelectric point similar to those of fibroblast growth factor (FGF-2), was coprecipitated with calcium phosphates in the presence or absence of a hydroxyapatite ceramic (HAP) using supersaturated calcium phosphate solutions that can be prepared by mixing infusion fluids. The precipitates formed in the solution consisted of amorphous calcium phosphate in the absence of a HAP. In the presence of a HAP, precipitates morphologically identical to bone-like apatite formed a calcium phosphate layer on the surface of HAP. The optimum conditions for coprecipitation of cyt C with calcium phosphate on HAP were a Ca/P molar ratio of 1.5 and a NaHCO3 concentration of 7.90mM. The release of cyt C from the calcium phosphate layer continued for at least 10 days in the physiological salt solution. The results suggest that FGF-2 is also expected to be coprecipitated with calcium phosphates onto HAPs using infusion fluids. [Copyright &y& Elsevier]

Abstract: Calcium phosphate is a suitable carrier of zinc, an essential element that has stimulatory effects on bone formation in vitro and in vivo as well as an inhibitory effect on osteoclastic bone resorption in vitro. The highest zinc content is attained in β-tricalcium phosphate, where the zinc content reaches 6wt%. Both rat and human bone marrow cells (BMCs) cultured on zinc-containing β-tricalcium phosphate and hydroxyapatite composite ceramics differentiated more than BMCs cultured on zinc-free composite ceramics in the presence of β-glycerophosphate and dexamethasone. The acceptable dose of zinc was higher for human BMCs than for rat BMCs. The solubility of ZnTCP, which contains a nontoxic level of zinc, decreased to 52–92% that of pure TCP in the pH range of 5.0–7.4. However, the resorbed volume of ZnTCP was much lower than that expected from the in vitro solubility of ZnTCP, becoming as low as 26–20% that of TCP, which indicates that the reduction in the resorbability of ZnTCP would be attributable principally to its lowered cellular activation property relative to that associated with pure TCP. Probably due to the lowered cellular activation property associated with ZnTCP, bone loss at the bone-implant interface was significantly arrested in the long-term implantation of ZnTCP/HAP. The intramuscular injection of ZnTCP powder is effective in increasing bone mineral density in the vicinity of the injected site in osteopenic animals. All these findings suggest that zinc-containing calcium phosphate is a biomaterial that promotes bone formation. [Copyright &y& Elsevier]

Abstract: Zinc is an essential trace element with stimulatory effects on bone formation in vitro and in vivo. In order to apply zinc-containing α-tricalcium phosphate (αZnTCP) to αTCP-based calcium phosphate cement, αZnTCP powders containing various amounts of zinc were prepared and the optimum zinc content was examined from the viewpoints of hydrolysis property and cytocompatibility. Single-phase αZnTCP containing zinc from 0.00 to 1.26 wt.% was obtained by heating zinc-containing β-tricalcium phosphate at 1450 °C. At a zinc content of 0.11 wt.%, there was no significant difference in the amount of calcium-deficient low-crystalline apatite formed by hydrolysis between pure αTCP and αZnTCP. The hydrolysis of αZnTCP was significantly retarded by incorporating zinc at or more than 0.26 wt.% due to the inhibitory effect of zinc on the crystal growth of apatite. The MC3T3-E1 cell densities cultured with pure αTCP and 0.11 Zn wt.% αZnTCP powders showed no significant difference in the range of powder dose from 10 to 1000 μg mL−1. The result indicated that the cytocompatibility of pure αTCP powder was comparable to that of αZnTCP at the zinc content of 0.11 wt.%. Therefore, the optimum zinc content of αZnTCP powder is less than 0.26 wt.%, and preferably at or less than 0.11 wt.% to apply to an αTCP-based calcium phosphate cement. [Copyright &y& Elsevier]

Zinc-containing tricalcium phosphate (ZnTCP) is biocompatible and bioactive, and functions as an effective zinc carrier. ZnTCP contains a maximum of 12 mol% of zinc. ZnTCP ceramics and composite ceramics of ZnTCP and hydroxyapatite (ZnTCP/HAP) with a (Ca+Zn)/P molar ratio of 1.60 were prepared by sintering at 1100 °C. ZnTCP/HAP continued to release zinc for more than 50 days in 0.9 wt.% sodium chloride solution. ZnTCP/HAP with a zinc content of 1.2 wt.% significantly increased osteoblastic MC3T3-E1 cell proliferation and alkaline phosphatase activity of rat stromal cells in vitro. ZnTCP/HAP with a zinc content of 0.316 wt.% increased bone formation by 51% (n=6; p=0.0509) 4 weeks after implantation in rabbit compared to the control without zinc. A zinc concentration within a noncytotoxic level of a solution does not completely block the crystal growth of apatite in the solution. When ZnTCP is added to calcium phosphate cement, the ZnTCP showed neither inhibitory nor promoting effect on the setting ability of the cement. All these findings suggest that the zinc-containing tricalcium phosphate is a biomaterial that has a pharmaceutical effect of promoting bone formation. [Copyright &y& Elsevier]

Background: The risk of impaired bone–pin interface strength in titanium (Ti) pins coated with fibroblast growth factor (FGF)–calcium phosphate (CP) composite layers is yet to be evaluated in a clinical study. This retrospective study used Weibull plot analysis to evaluate bone–pin interface strength in Ti pins coated with FGF-CP layers for external distal radius fracture fixation. Methods: The distal radial fractures were treated with external fixation. The FGF-CP group comprised five patients (all women, aged 70.4 ± 5.9 (range: 62–77) years), and the uncoated pin group comprised ten patients (eight women and two men, aged 64.4 ± 11.7 (range: 43–83) years). The pins were removed after six weeks. The insertion and extraction peak torques were measured. The extraction peak torque was evaluated using Weibull plot analysis. Results: We compared the extraction torque of the two groups at or below 506 Nmm for a fair comparison using Weibull plot analysis. The Weibull plots were linear for both the FGF-CP and uncoated pin groups. The slope of the regression line was significantly higher in the FGF-CP group (1.7343) than in the uncoated pin group (1.5670) (p = 0.011). The intercept of the regression line was significantly lower in the FGF-CP group (−9.847) than in the uncoated pin group (−8.708) (p = 0.002). Thus, the two regression lines significantly differed. Conclusions: Ti pins coated with FGF-CP layers exhibit the potential to reduce the risk of impaired bone–pin interface strength in the external fixation of distal radius fractures. [ABSTRACT FROM AUTHOR]

Hollow Gd2O3 nanospheres significantly promote the cellular uptake of a tumor antigen by antigen presenting cells, exhibit pH-dependent alteration of the MR signal intensity and markedly enhance the antitumor immunity. Hollow Gd2O3 nanospheres are promising as magnetic resonance imaging (MRI)-visible cancer immunoadjuvants for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Vaccines, one of the most effective and powerful public health measures, have saved countless lives over the past century and still have a tremendous global impact. As an indispensable component of modern vaccines, adjuvants play a critical role in strengthening and/or shaping a specific immune response against infectious diseases as well as malignancies. The application of nanotechnology provides the possibility of precisely tailoring the building blocks of nanoadjuvants towards modern vaccines with the desired immune response. The last decade has witnessed great academic progress in inorganic nanomaterials for vaccine adjuvants in terms of nanometer-scale synthesis, structure control, and functionalization design. Inorganic adjuvants generally facilitate the delivery of antigens, allowing them to be released in a sustained manner, enhance immunogenicity, deliver antigens efficiently to specific targets, and induce a specific immune response. In particular, the recent discovery of the intrinsic immunomodulatory function of inorganic nanomaterials further allows us to shape the immune response towards the desired type and increase the efficacy of vaccines. In this article, we comprehensively review state-of-the-art research on the use of inorganic nanomaterials as vaccine adjuvants. Attention is focused on the physicochemical properties of versatile inorganic nanoadjuvants, such as composition, size, morphology, shape, hydrophobicity, and surface charge, to effectively stimulate cellular immunity, considering that the clinically used alum adjuvants can only induce strong humoral immunity. In addition, the efforts made to date to expand the application of inorganic nanoadjuvants in cancer vaccines are summarized. Finally, we discuss the future prospects and our outlook on tailoring inorganic nanoadjuvants towards next-generation vaccines. [ABSTRACT FROM AUTHOR]

Stellated fibrous mesoporous silica nanospheres significantly improve the cellular uptake of cancer antigen and the maturation of bone marrow derived dendritic cells in vitro. Moreover, the combination of poly(I:C) with stellated fibrous MS nanospheres markedly decreases the necessary dose of poly(I:C) for anti-tumor immunity, and thus opens new opportunities for the future clinical application of poly(I:C) in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

To solve the instrument loosening problem, we developed a fibroblast growth factor-2-calcium phosphate composite layer as a novel coating material to improve screw fixation strength. The primary aim of the present study was to demonstrate the safety and feasibility of screws coated with the FGF-2-calcium phosphate composite layer for posterior instrumented surgery of the cervical spine. The trial design was a single-arm, open-label, safety and feasibility study. Patients receiving fusion of the cervical spine from C2 (or C3) to C7 (or T1) were recruited. The primary endpoint to confirm safety was any screw-related adverse events. Seven patients who underwent posterior fusion surgery of the cervical spine were enrolled in the present study. The coated pedicle screws were inserted bilaterally into the lowest instrumented vertebrae. There was only one severe adverse event unrelated with the coated screw. Three out of the fourteen coated screws showed loosening. The present results prove the safety and feasibility of pedicle screws coated with the FGF-2-calcium phosphate composite layer for fusion surgery in the cervical spine. This is the first step to apply this novel surface coating in the field of spine surgery. [ABSTRACT FROM AUTHOR]

Herein, rod-shaped and fluorine-substituted hydroxyapatite nanoparticles (FHA) were synthesized using a facile hydrothermal method. The rod-shaped FHA significantly increased the cellular uptake of a model antigen by bone marrow dentritic cells in vitro, improved antigen presentation in vivo, stimulated immune-related cytokine secretion in vitro and ex vivo, and enhanced the anti-cancer immunity in vivo. [ABSTRACT FROM AUTHOR]

A Th1 immune response is required for modern vaccines as the most commonly used alum adjuvant has weak capacity for inducing Th1 immune response. Herein, rod-shaped hydroxyapatite (HA), magnesium-substituted HA (MgHA) and zinc-substituted HA (ZnHA) nanoparticles with irregular nanopores were synthesized and used as immunoadjuvants. Magnesium and zinc substitution in HA showed no influence on morphology, particle size, zeta potential and surface area of the nanoparticles. The rod-shaped MgHA and ZnHA nanoparticles promoted the cellular uptake of a molecular immunopotentiator, stimulated both type 1 and 2 cytokine secretion in vitro that relate to Th1 and Th2 immunity of bone marrow dentritic cells, respectively. The MgHA and ZnHA nanoparticles may be useful as immunoadjuvants for human. [ABSTRACT FROM AUTHOR]

The use of appropriate adjuvants that support the generation of robust and long-lasting antitumor immune responses is crucial for tumor immunotherapy owing to the immunosuppressive environment of the growing tumor. However, the most commonly used adjuvant, aluminum hydroxide, is ineffective for generating such immune responses and therefore not suitable for cancer immunotherapy. It is now shown that plain hollow mesoporous silica nanospheres markedly improve the antitumor immunity, the Th1 and Th2 immunity, and the CD4+ and CD8+ effector memory T cell population in bone marrow in vivo and may thus be used as immunoadjuvants to treat cancer in humans. [ABSTRACT FROM AUTHOR]

The use of appropriate adjuvants that support the generation of robust and long-lasting antitumor immune responses is crucial for tumor immunotherapy owing to the immunosuppressive environment of the growing tumor. However, the most commonly used adjuvant, aluminum hydroxide, is ineffective for generating such immune responses and therefore not suitable for cancer immunotherapy. It is now shown that plain hollow mesoporous silica nanospheres markedly improve the antitumor immunity, the Th1 and Th2 immunity, and the CD4+ and CD8+ effector memory T cell population in bone marrow in vivo and may thus be used as immunoadjuvants to treat cancer in humans. [ABSTRACT FROM AUTHOR]

A plasma- and precursor-assisted biomimetic process utilizing plasma and alternate dipping treatments was applied to a Leeds-Keio artificial ligament to produce a thin coating of apatite in a supersaturated calcium phosphate solution. Following plasma surface modification, the specimen was alternately dipped in calcium and phosphate ion solutions three times (alternate dipping treatment) to create a precoating containing amorphous calcium phosphate (ACP) which is an apatite precursor. To grow an apatite layer on the ACP precoating, the ACP-precoated specimen was immersed for 24 h in a simulated body fluid with ion concentrations approximately equal to those in human blood plasma. The plasma surface modification was necessary to create an adequate apatite coating and to improve the coating adhesion depending on the plasma power density. The apatite coating prepared using the optimized conditions formed a thin-film that covered the entire surface of the artificial ligament. The resulting apatite-coated artificial ligament should exhibit improved osseointegration within the bone tunnel and possesses great potential for use in ligament reconstructions. [ABSTRACT FROM AUTHOR]

To improve the biocompatibility, inter-connective pore structure, and drug delivery ability of self-setting apatite/collagen composite cement (ACC), a three-dimensionally perforated porous apatite/collagen composite cement (TPPACC) containing 3% indomethacin (IMC) was obtained in an arranged multi-cross with 20, 40, and 60 stainless steel needlelike male dies, and stored and hardened at 37°C and 100% relative humidity for 24 h. The mean radius of micro-pores of the TPPACC was evaluated to be 0.125 µm by mercury porosimetry. X-ray powder diffraction and FT-IR spectroscopy suggested that TPPACC consisted of carbonated apatite and had a structure similar to that of natural rat bone. The IMC release rates from a TPPACC block containing the drug were measured in simulated body fluid. The rate of release increased with the number of macro-pores that from planar surface matrix systems followed the Higuchi equation. The relationship between the Higuchi constant and surface area of TPPACC showed a straight line with K = 0.2123 and R2 = 0.9892. These results indicated that the rate of drug release from TPPACC could be controlled by the number of macro-pores for bone cells. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:286–292, 2010 [ABSTRACT FROM AUTHOR]

Abstract: The final aim of our study is to develop a novel calcium phosphate cement based on zinc-containing α-tricalcium phosphate (αZnTCP) and evaluate its potential as bonegraft material in vivo. In the present study, in vivo efficacy of zinc in hardened bodies of αZnTCP was explored. The hardened bodies prepared from αZnTCP with zinc content of 0.00, 0.04, 0.08, 0.11 and 0.19 wt.% were prepared by mixing pure αTCP or αZnTCP powder with 12 wt.% sodium succinate solution at a solid-to-liquid ratio of 2.0. Due to the release of zinc ions into the physiological salt solution during curing, the zinc content in the hardened bodies was calculated to be 0.00, 0.03, 0.06, 0.10 and 0.18 wt.%, respectively. The hardened bodies were implanted in the femora and tibia of white rabbits for 4 weeks. Histological and histomorphometric evaluation showed that the hardened body containing 0.03 wt.% zinc, significantly promoted more new bone formation without evoking adverse tissue reactions than that without zinc. The hardened bodies containing 0.06 and 0.10 wt.% zinc also resulted in the increase in numbers of active osteoblasts surrounding the new bone but caused inflammation at the implant sites. Results of this study indicate that the hardened body prepared with αZnTCP is superior to that prepared with αTCP in promoting new bone formation due to the release of zinc ions. This study also indicates that the optimum amount of zinc in the hardened body is about 0.03 wt.% to avoid inflammatory reaction. [Copyright &y& Elsevier]

Abstract: Fibroblast growth factor-2 (FGF-2) apatite composite layers were formed on anodically oxidized titanium (Ti) rods at temperatures lower than the previously used 37 °C to reduce the risk of the inactivation of FGF-2 in calcium phosphate solution. A two-step procedure was used to coprecipitate FGF-2 apatite composite layers on Ti rods. Continuous and homogeneous carbonate-containing low-crystalline apatite layers incorporating FGF-2 were formed on the surface of the Ti. The amounts of apatite and FGF-2 coprecipitated on the Ti rod surface decreased with decreasing coprecipitation temperature. When the coprecipitation temperatures were 15 and 20 °C, the amounts of FGF-2 precipitated on the Ti rods were 0.19±0.03 and 0.20±0.03 μg/cm2, respectively. A cell proliferation assay for evaluating the mitogenic activity of FGF-2 immobilized in the layer showed that when FGF-2 was coprecipitated at 15 and 20 °C, the number of NIH3T3 cells cultured with FGF-2 extract was significantly larger than that at 4, 10, 25 and 30 °C. To obtain the largest amount of active FGF-2 on a Ti surface, a temperature of 15 or 20 °C should be used for coprecipitating FGF-2. [Copyright &y& Elsevier]

We developed a novel technique of hybridizing calcium phosphate (CaP) with bioorganic soft tissue using an alternating soaking process. By this technique, we hybridized CaP with a grafted tendon tissue to bond with a bone tunnel. Tendons were soaked in Ca and NaHPO4 solutions alternately for 10 min. Needle-like CaP crystals 30–50 nm in length including low-crystalline apatite were deposited on and between collagen fibrils from the surface to 200 μm deep in the tendon. In light and transmission electron microscopic images, osteoclast-like cells and osteoblasts appeared on the implanted tendon and osteoid was observed on the tendon surface at 1 week postoperatively. At 2 weeks postoperatively, osteoclast-like cells resolved the tendon by forming Howship''s lacuna-like spaces on the surfaces and osteoblasts formed osteoid in these spaces. Direct bonding between the implanted tendon and the newly formed bone was observed. At 3 weeks postoperatively, thick newly formed bone firmly bonded to tendon surface. From these results, we conclude that the tendons prepared by an accelerated CaP hybridization method efficiently enhance osteoclast-like cells and osteoblasts to bond the implanted tendons to newly formed bone. [Copyright &y& Elsevier]

The article presents a study which examined the characteristics of tin oxide. Transparent electrically conductive oxide films exhibit a high transmittance in the visual region and a high reflectivity in the infrared region. They have a high level of electrical conductivity. The advantages of these excellent properties have been utilized for opto-electrical devices, freezer showcases and heat-reflecting glasses.

Ionizing radiation exposure may not only cause acute radiation syndrome, but also an increased risk of late effects. It has been hypothesized that induction of chronic oxidative stress mediates the late effects of ionizing radiation. However, only a few reports have analyzed changes in long-term antioxidant capacity after irradiation in vivo. Our previous study demonstrated changes in whole-blood antioxidant capacity and red blood cell (RBC) glutathione levels within 50 days after total body irradiation (TBI). In this study, seven-week-old, male, C57BL/6J mice exposed to total body irradiation by X-ray and changes in whole-blood antioxidant capacity and RBC glutathione levels at ≥ 100 days after TBI were investigated. Whole-blood antioxidant capacity was chronically decreased in the 5-Gy group. The RBC reduced glutathione (GSH) level and the GSH/oxidative glutathione (GSSG) ratio were chronically decreased after ≥ 1 Gy of TBI. Interestingly, the complete blood counts (CBC) changed less with 1-Gy exposure, suggesting that GSH and the GSH/GSSG ratio were more sensitive radiation exposure markers than whole-blood antioxidant capacity and CBC counts. It has been reported that GSH depletion is one of the triggers leading to cataracts, hypertension, and atherosclerosis, and these diseases are also known as radiation-induced late effects. The present findings further suggest that chronic antioxidant reduction may contribute to the pathogenesis of late radiation effects. [ABSTRACT FROM AUTHOR]

Graphical abstract Si-doping in HA nanorods increases adjuvant activity, promotes maturation and cytokine secretion of BMDCs, increases both Th1 and Th2 cytokines secretion. Highlights • Si-doping in HA nanorods increases adjuvant activity. • Si-doping in HA nanorods promotes maturation and cytokine secretion of BMDCs. • Si-doping in HA increases both Th1 and Th2 cytokines secretion. • Si-doped HA accelerates antigen delivery in lymph node in vivo. Abstract Recombinant protein-based vaccines generally show limited immunogenicity and need adjuvants to achieve robust immune responses. Herein, to combine the excellent biocompatibility of hydroxyapatite (HA) and exciting adjuvant activity of silica, Si-doped HA nanorods with Si/P molar ratio from 0 to 0.65 were hydrothermally synthesized and evaluated as immunoadjuvants. Si-doping decreases the size and increases the BET surface area of the nanorods. Si-doping in HA nanorods increases the in vitro adjuvant activity, including CD11c+CD86+ expression and cytokine secretion of bone marrow derived dendritic cells (BMDCs). Moreover, Si-doping in HA increases the ex vivo adjuvant activity as shown by the increase in both Th1 and Th2 cytokines secretion. Si-doped HA nanorods are promising as a new immunoadjuvant. [ABSTRACT FROM AUTHOR]

Herein, mesoporous silica-zinc oxide (MS-Zn) micro-rosettes with controllable petal thickness were synthesized by a facile one-pot hydrothermal method. MS-Zn loaded with doxorubicin and polyinosinic–polycytidylic acid sodium salt not only significantly inhibits tumor growth but also effectively rejects tumor metastasis in vivo. [ABSTRACT FROM AUTHOR]

• Microstructures on 3Y-TZP surface enhances osteogenic differentiation of ADSCs. • Microstructures on 3Y-TZP surface reduces cell attachment area of ADSCs. • Microstructures on 3Y-TZP surface could be useful for bone tissue engineering. Zirconia substrates with periodic surface microstructures formed by irradiation with a femtosecond laser previously enhanced osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs), associated with a reduction in the cell attachment area. Adipose-derived mesenchymal stem cells (ADSCs) are clinically less difficult in harvesting the cells than BMSCs. In this study, we investigated the effects of zirconia substrates with the periodic surface microstructures on osteogenic differentiation of rat ADSCs. Zirconia substrates with the periodic surface microstructures enhanced not adipogenic differentiation but osteogenic differentiation of rat ADSCs, associated with a reduction in the cell attachment area. Therefore, zirconia substrates with surface periodic microstructures formed by irradiation with a femtosecond laser could be useful in bone tissue engineering using ADSCs when BMSCs are unavailable. [ABSTRACT FROM AUTHOR]

Yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) have been used in orthopedic and dental implants because of their excellent physicochemical properties. In this study, we developed an apatite coating technique with low thermal effects for Y-TZP ceramics based on a biomimetic process using a supersaturated calcium phosphate solution (CP solution) as a coating medium. To achieve this, we performed femtosecond laser processing with low thermal effects as a surface pre-modification tool for Y-TZP ceramics. By changing the laser scanning mode, we fabricated two different submicro-/micro-structures on the Y-TZP sample. Both laser-treated samples showed increased water wettability due to ablation plasma and partly formed an apatite layer on their surfaces in the CP solution within 7 days. To further enhance the apatite-forming ability, we applied an alternate dipping process to the laser-treated sample in order to precoat the sample with apatite precursors. The laser-treated and precursor-precoated sample successfully formed an apatite layer on the entire surface in the CP solution within a shorter time period (24 h). The thus-coated apatite layer adhered to the sample so strongly that the layer remained on the sample even after the tape-detaching test. This strong adhesion may be attributed to the mechanical interlocking effects due to laser-induced surface roughening. Our proposed apatite-coating technique using the laser- and precursor-assisted biomimetic process would be useful for the creation of apatite-coated Y-TZP ceramics for orthopedic and dental applications. [ABSTRACT FROM AUTHOR]

Yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) have been used in orthopedic and dental implants because of their excellent physicochemical properties. In this study, we developed an apatite coating technique with low thermal effects for Y-TZP ceramics based on a biomimetic process using a supersaturated calcium phosphate solution (CP solution) as a coating medium. To achieve this, we performed femtosecond laser processing with low thermal effects as a surface pre-modification tool for Y-TZP ceramics. By changing the laser scanning mode, we fabricated two different submicro-/micro-structures on the Y-TZP sample. Both laser-treated samples showed increased water wettability due to ablation plasma and partly formed an apatite layer on their surfaces in the CP solution within 7 days. To further enhance the apatite-forming ability, we applied an alternate dipping process to the laser-treated sample in order to precoat the sample with apatite precursors. The laser-treated and precursor-precoated sample successfully formed an apatite layer on the entire surface in the CP solution within a shorter time period (24 h). The thus-coated apatite layer adhered to the sample so strongly that the layer remained on the sample even after the tape-detaching test. This strong adhesion may be attributed to the mechanical interlocking effects due to laser-induced surface roughening. Our proposed apatite-coating technique using the laser- and precursor-assisted biomimetic process would be useful for the creation of apatite-coated Y-TZP ceramics for orthopedic and dental applications. [ABSTRACT FROM AUTHOR]

Surface-mediated gene delivery systems have many potential applications in tissue engineering. We recently fabricated an assembly consisting of DNA–amorphous calcium phosphate (DNA–ACP) nanocomposite spheres on a polymer substrate via coprecipitation in a labile supersaturated calcium phosphate (CaP) solution and demonstrated the assembly’s high gene delivery efficacy. In this study, we conducted a detailed investigation of the coprecipitation process in solution and revealed that the negatively charged DNA molecules were immobilized in the ACP spheres during the initial stage of coprecipitation and functioned as both sphere-dispersing and size-regulating agents. As a result, the DNA–ACP nanocomposites grew into size-regulated submicrospheres in solution and assembled onto the substrate via gravity sedimentation. The assembled nanocomposite spheres were chemically anchored to the substrate surface through an intermediate layer of CaP-based nanoparticles that was formed heterogeneously at the substrate surface. The coprecipitation conditions, i.e. , coprecipitation time and Ca and P concentrations in solution, greatly affected the state of assembly of the nanocomposite spheres, thereby influencing the gene expression level of the cells cultured on the substrate. Increasing the number density and decreasing the size of the nanocomposite spheres did not always increase the assembly’s gene delivery efficacy (per surface area of the substrate) due to adverse effects on cellular viability. As demonstrated herein, controlling the coprecipitation conditions is important for designing a cell-stimulating and biocompatible scaffold surface consisting of an assembly of DNA–ACP nanocomposite spheres. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of the present study is to evaluate the efficacy of slow zinc (Zn) release from β-tricalcium phosphate powder (ZnTCP) containing 10 mol% Zn on rats with thermal burns.METHODS: The first-aid tapes were contained zinc sulfate (ZnSO4) solution, ZnTCP suspensions or zinc oxide ointment. After thermal burn treatments were performed on Zn-deficient rats, the groups D1, D2 and D3 were treated with tapes containing ZnTCP, ZnSO4 and zinc oxide ointment. The effects of the tapes on wound area, plasma Zn levels and alkaline phosphatase activity (Alp) were investigated.RESULTS: The wound area profiles of all rat groups could be separated into before and after the scab formation at around day 6. The area under the curve (Aw-AUC) for wound area profiles, therefore, was evaluated as an index of therapeutic scores for the thermal wound. The order of Aw-AUC was D3>C>D2>D1. The degree of expansion at the initial stage by thermal burns of group D1 was the lowest and that of group D2 was the highest, and the order was D1

Surface-mediated nonviral gene transfer systems using biocompatible apatite-based composite layers have potential use in tissue engineering applications. Herein, we investigated a relatively efficient system based on a DNA-lipid-apatite composite layer (DLp-Ap layer): an apatite (Ap) layer with immobilized DNA and lipid (Lp) complexes (DLp complexes). DLp-Ap layers were fabricated on substrates using supersaturated calcium phosphate coprecipitation solutions supplemented with DLp complexes, and the molecular compositions of the DLp-Ap layers were controlled by varying the net DNA concentrations and Lp/DNA ratios in the coprecipitation solutions. Increases in both the DNA concentration and Lp/DNA ratio in the coprecipitation solution increased the DLp complex content of the resulting DLp-Ap layer. However, a higher DLp complex content did not always provide increased gene transfer efficiency to the CHO-K1 cells, because there was a threshold content of approximately 10 μg/cm 2 . In addition, DLp-Ap layers with similar DLp complex contents exhibited different gene transfer efficiencies, most likely due to the different Lp/DNA ratios in the layers. Notably, the optimized Lp/DNA ratios in the coprecipitation solutions for maximizing the gene transfer efficiency were lower than those of the conventional particle-mediated lipofection systems. These findings will serve as a useful design guide for the preparation of DLp-Ap layers with high gene transfer efficiency. [ABSTRACT FROM AUTHOR]

Apatite can mediate gene transfer into cells by serving as a safe and biocompatible immobilization matrix for DNA and transfection reagents. Recently, an apatite layer that immobilized DNA-lipid complexes was prepared by a coprecipitation process in a supersaturated calcium phosphate solution. This composite layer (DNA–lipid–apatite layer) showed a higher gene transfer capability than an apatite layer with superficially adsorbed DNA-lipid complexes (DNA-lipid-adsorbed apatite layer). In this study, the DNA–lipid–apatite layer and the DNA-lipid-adsorbed apatite layer were compared for their physicochemical properties and gene transfer capabilities. The higher gene transfer capability of the DNA–lipid–apatite layer compared with that of the DNA-lipid-adsorbed apatite layer was reconfirmed by a luciferase assay using epithelial-like CHO-K1 cells. Physicochemical structure analyses showed that the DNA–lipid–apatite layer possessed a larger capacity for DNA-lipid complexes than the DNA-lipid-adsorbed apatite layer. The DNA–lipid–apatite layer released DNA-lipid complexes in a slow and sustained manner, whereas the DNA-lipid-adsorbed apatite layer released them in short bursts. Consequently, the release of DNA-lipid complexes from the DNA–lipid–apatite layer was larger in amount and longer in duration than release from the DNA-lipid-adsorbed apatite layer. This difference in release profiles may be responsible for the higher gene transfer capability of the DNA–lipid–apatite layer compared with that of the DNA-lipid-adsorbed apatite layer. The coprecipitation process and the resulting DNA–lipid–apatite layer have many applications in tissue engineering. [ABSTRACT FROM AUTHOR]

Submicrospheres composed of amorphous calcium phosphate (ACP) and DNA spontaneously assembled on a substrate via homogeneous calcium phosphate (CaP) nucleation followed by deposition in a highly supersaturated labile CaP solution. The nanocomposite layer of sphere assembly showed higher gene transfer efficiency than a continuous film nanocomposite layer previously fabricated via heterogeneous nucleation in a metastable supersaturated solution. [ABSTRACT FROM AUTHOR]

A tissue-engineered endothelial layer was prepared by culturing endothelial cells on a fibroblast growth factor-2 (FGF-2)-l-ascorbic acid phosphate magnesium salt n-hydrate (AsMg)-apatite (Ap) coated titanium plate. The FGF-2-AsMg-Ap coated Ti plate was prepared by immersing a Ti plate in supersaturated calcium phosphate solutions supplemented with FGF-2 and AsMg. The FGF-2-AsMg-Ap layer on the Ti plate accelerated proliferation of human umbilical vein endothelial cells (HUVECs), and showed slightly higher, but not statistically significant, nitric oxide release from HUVECs than on as-prepared Ti. The endothelial layer maintained proper function of the endothelial cells and markedly inhibited in vitro platelet adhesion. The tissue-engineered endothelial layer formed on the FGF-2-AsMg-Ap layer is promising for ameliorating platelet activation and thrombus formation on cardiovascular implants. [ABSTRACT FROM AUTHOR]

Abstract: Although fibroblast growth factor 2 (FGF2) is a promising agent for treating brain infarction, current methods of FGF2 administration are associated with a short circulating half-life. An FGF2 apatite coating was developed as a slow-releasing drug delivery system (DDS) by forming an FGF2/calcium phosphate composite layer. Hydroxyapatite was coated with high or low doses of FGF2, denoted as FGF-high and FGF-low. This study investigated the efficacy of the coating as angiogenesis therapy for brain infarction. Rats were subjected to permanent occlusion of the middle cerebral artery, an FGF2 apatite-coated implant was inserted, and the rat brains were removed 2weeks after implantation. Rats in groups treated with FGF-high had significantly smaller areas of brain infarction, particularly in the external capsule and the lateral side of the putamen, and better capillary density than rats in groups treated with non-FGF2 apatite-coated implants. Histologic analysis indicated that the new vessels were larger and had thicker walls in the FGF2 apatite-coated groups than in the non-FGF2 groups. Fluorescence immunohistochemistry of the peri-infarction region showed that FGF2 released from FGF2 apatite-coated implants might have biological activity. Moreover, fluorescence immunohistochemistry showed that released FGF2 influenced microglia cells. This new FGF2 DDS involving an FGF2 apatite coating can prevent infarction of the penumbra through the multipotential effects of FGF2. [Copyright &y& Elsevier]

Abstract: The initial attachment of mesenchymal stem cells (MSCs) to substrates and osteogenic differentiation are supported by culture on a hydroxyapatite substrate. Cell attachment areas of rat MSCs after 2h of culture on hydroxyapatite substrates with various microstructures and the osteogenic differentiation activity thereafter were measured. The perceived outcome was that, after 2h of culture, rat MSCs with a small attachment area would have a high osteogenic differentiation activity, whereas those with a large attachment area would have a low osteogenic differentiation activity. Furthermore, rat MSCs with a small attachment area had many cytoplasmic processes, while those with a large attachment area revealed clear stress fibers and focal contacts. These results suggest that cell attachment area of rat MSCs after 2h of culture has a strong effect on the osteogenic differentiation of rat MSCs. Thus, the measurement of cell attachment area after 2h of culture could become valuable for estimating the osteogenic differentiation activity of rat MSCs thereafter. [Copyright &y& Elsevier]

Cell morphology has received considerable attention in recent years owing to its possible relationship with cell functions, including proliferation, differentiation, and migration. Recent evidence suggests that extracellular environments can also mediate cell functions, particularly cell adhesion. The aims of this study were to investigate the correlation between osteogenic differentiation activity and the morphology of rat mesenchymal stromal cells (MSCs), and to develop a method of estimating osteogenic differentiation capability of MSCs on biomaterials. We measured the attachment areas of MSCs on substrates with various types of surface after 2 h of seeding, and quantified the amount of osteocalcin secreted from MSCs after 3 weeks of culture under osteogenic differentiation conditions. MSCs with small attachment areas showed a high osteogenic differentiation activity. These findings indicate that cell attachment areas correlate well with the osteogenic differentiation activity of MSCs. They also suggest that the measurement of cell attachment areas is useful for estimating the osteogenic differentiation activity of MSCs and is a practical tool for applications of MSCs in regenerative medicine. [ABSTRACT FROM AUTHOR]

Surface-mediated gene transfer systems using apatite (Ap)-based composite layers have received increased attention in tissue engineering applications owing to their safety, biocompatibility and relatively high efficiency. In this study, DNA-antibody-apatite composite layers (DA-Ap layers), in which DNA and antibody molecules are immobilized within a matrix of apatite nanocrystals, were fabricated using a biomimetic coating process. They were then assayed for their gene transfer capability for application in a specific cell-targeted gene transfer. A DA-Ap layer that was fabricated with an anti-CD49f antibody showed a higher gene transfer capability to the CD49f-positive CHO-K1 cells than a DNA-apatite composite layer (D-Ap layer). The antibody facilitated the gene transfer capability of the DA-Ap layer only to the specific cells that were expressing corresponding antigens. When the DA-Ap layer was fabricated with an anti-N-cadherin antibody, a higher gene transfer capability compared with the D-Ap layer was found in the N-cadherin-positive P19CL6 cells, but not in the N-cadherin-negative UV♀2 cells or in the P19CL6 cells that were pre-blocked with anti-N-cadherin. Therefore, the antigen-antibody binding that takes place at the cell-layer interface should be responsible for the higher gene transfer capability of the DA-Ap than D-Ap layer. These results suggest that the DA-Ap layer works as a mediator in a specific cell-targeted gene transfer system. [ABSTRACT FROM AUTHOR]

Abstract: Gene transfer techniques are useful tools for controlling cell behavior, such as proliferation and differentiation. We have recently developed an efficient area-specific gene transfer system using a DNA–fibronectin–apatite composite layer (DF-Ap layer). In this system, partial dissolution of the composite layer is likely to be a crucial step for gene transfer. In the present study, layer solubility was adjusted by incorporating various contents of carbonate or fluoride ions into the DF-Ap layer via ionic substitution for the apatite crystals. Carbonate ion incorporation increased the solubility of the DF-Ap layer, thereby increasing the efficiency of gene transfer on the layer. In contrast, the incorporation of fluoride ions decreased the solubility of the DF-Ap layer, thereby decreasing the efficiency and delaying the timing of gene transfer on the layer dose-dependently. The present gene transfer system with controllable efficiency and timing would be useful in tissue engineering applications because cell differentiation can be induced effectively by regulating appropriate gene expression with suitable timing. [Copyright &y& Elsevier]

Abstract: Surface-induced thrombosis is a major complication associated with blood-contacting biomaterials. Cross-linked albumin films possessing native albumin characteristics such as resistance to cell adhesion and drug binding ability are available for improving the blood compatibility of biomaterial surfaces. In the present study, we aimed to evaluate the blood compatibility of cross-linked albumin films. Platelet adhesion analysis showed that albumin film coated substrates exhibited very low platelet adhesion, and platelet adhesion was further suppressed by loading the antiplatelet drug, cilostazol, into the film. Monitoring the coagulation process of whole blood using a coaxial-cylinder rotational viscometer showed that the initial time of coagulation in albumin film coated cylinders was delayed compared with that in uncoated cylinders, suggesting that activation of the intrinsic coagulation cascade was reduced on the albumin film coated surface. Thus, surface coating with cross-linked albumin films is a promising approach to conferring biomaterials with antithrombogenic surfaces due to the resistance to platelet adhesion and the antiplatelet drug-releasing capability afforded by the films. [Copyright &y& Elsevier]

To realize real-time evaluation of human platelet adhesions onto material surfaces with small volumes of human platelet suspensions, we developed an apparatus consisting of a modified cone and plate-type viscometer, combined with an upright epi-fluorescence microscope. The apparatus allowed real-time evaluation of platelet–material interactions and the initial event of thrombus formation, using small platelet suspension volumes (7.5 µL) under shear flow conditions. To study the dynamic behavior of platelet–material interaction, we chose five representative opaque and transparent materials: acrylate resin (AC), polytetrafluoroethylene (PTFE), polyvynylchrolide (PVC), glass, and a monolayer of human normal umbilical cord vein endothelial cells (EC) on glass under shear flow conditions. The values of adhesiveness of human platelets to the test materials in descending order were as follows: AC > PTFE > PVC > glass > human EC. Under this new small-scale flow system, we could obtain highly reproducible data, which were comparable with results from a previously developed large-scale flow system. Therefore, the newly developed cone and plate-type rheometer is a useful instrument for testing and screening materials, and allows precise quantitative evaluation of human platelet adhesion. [ABSTRACT FROM AUTHOR]

Abstract: A polymeric material with a laminin–apatite composite (L–Ap) layer on its surface would be useful as a material for percutaneous devices with improved cell-adhesion properties and good biocompatibility. Such a laminin–apatite-polymer composite can be prepared using a liquid phase coating process. In this study, the mechanical properties of an L–Ap layer formed on an ethylene–vinyl alcohol copolymer (EVOH) plate were evaluated and compared with those of an apatite (Ap) layer. The laminin immobilized in the L–Ap layer increased the layer''s shear strength under wet conditions. However, under dry conditions, there was no advantage of the laminin immobilization on the layer''s shear strength and adhesive strength to an EVOH plate. The adhesive strength of the layer to an EVOH plate improved as the thickness of the L–Ap layer decreased from 10 to 3 µm. From these results, it is suggested that a 3 µm thick L–Ap layer is better than a 10 µm thick L–Ap layer on an EVOH surface, and the resulting laminin–apatite–EVOH composite should not be dried when used as a material for percutaneous devices, to avoid any possible adverse effect of drying on the mechanical properties. [Copyright &y& Elsevier]

The purpose of this study was to evaluate the therapeutic efficacy of a new calcium phosphate (CaP)-based formulation in improving the bone mineral deficiency in ovariectomized (OVX) rats. The ions release experiments for CaP preparations (G2: 0.46% Mg, 5.78% Zn, and 2.5% F; G3:3.1% Mg, 0.03% Zn, and 3.01% F; G4: 1.25% Mg, 1.77% Zn, 1.35% F) and of a Zn-TCP (G1: 6.17% Zn) powders, the initial Mg and Zn ion release rates of MZF-CaPs were performed in acetate buffer at pH 4.5 (37°C). Wistar rats were divided into six groups including a normal (not OVX) group (GN) and a control, OVX group (GC). Rats in groups GC, G1, G2, G3, G4 were OVX. Suspensions consisting of CaP preparations (G2, G3, G4) and of a Zn-TCP (G1) powders were injected in the right thighs of OVX rats in all groups except for GN and GC, once a week for 4 weeks. GN and GC rats were injected with saline solutions. Plasma was analyzed for Zn land alkaline phosphatase levels. The bone mineral density (BMD) was measured using DEXA and the bone (femur) strength determined using three-point-bending analysis. G1 and G2 groups showed high plasma Zn levels. The area under the curve of plasma Zn was significantly greater in the G1, G2, and GN groups than in the G3, G4, and GC groups (p < 0.05). The BMD and bone mechanical strength of the right femur were significantly higher in the G1, G2, G3, and G4 groups than GC group on day 28. The right femur had significantly greater BMD and bone mechanical strength than the left femur in G1, G2, G3, and G4 groups. However, there was no significant difference in the BMD of the right femur between the G1, G2, G3, and G4 groups. Results indicate that the new injectable CaP formulations are effective in improving bone properties of OVX rats and may be useful in osteoporosis therapy. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:421–432, 2008 [ABSTRACT FROM AUTHOR]

Abstract: A percutaneous device with antibacterial activity and good biocompatibility is desired for clinical applications. Three types of antibacterial agent: lactoferrin (LF), tetracycline (TC), and gatifloxacin (GFLX) were immobilized on the surface of an ethylene-vinyl alcohol copolymer (EVOH) using a liquid phase coating process. In this process, an EVOH plate was alternately dipped in calcium and phosphate ion solutions, and then immersed in a metastable calcium phosphate solution supplemented with 4, 40, or 400μg/mL of the antibacterial agent. As a result, the antibacterial agent was immobilized on the EVOH surface in the form of an antibacterial agent–apatite composite layer. The amount of immobilized antibacterial agent increased with increasing absorption affinity for apatite in the order: GFLX