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Commonly used aluminum hydroxide (Alum) adjuvant provokes a strong type 2 helper T cell (Th2) response for mediating antibody production but is rather ineffective for disease prevention that requires type 1 helper T cell (Th1) response for mediating cellular immunity in human vaccination. Here, for the purpose of inducing Th1 antitumor immunity, a mesoporous silica (MS)-based adjuvant is prepared. Three kinds of MS particles with nearly identical particle size and surface area but different pore sizes of 4, 7 and 10 nm were prepared. No serious in vitro cytotoxicity was observed for the MS particles at 5, 20, 50, and 100 μg/mL. Pathogen-associated molecular patterns (PAMPs) were immobilized with apatite (Ap) on MS to prepare the MS-based and PAMP-loaded adjuvants (MS-Ap-PAMP adjuvants). Macrophage-like cells cultured in the presence of MS-Ap-PAMP adjuvant with a MS pore size of 10 nm showed the maximum in vitro immunogenic activity. Injection of the MS-Ap-PAMP adjuvant with a MS pore size of 10 nm in combination with liquid nitrogen-treated tumor tissue (derived from Lewis lung carcinoma cells) to C57BL/6 mice markedly inhibited the development of rechallenged tumor in vivo, while no such antitumor immunity was induced in injection of Alum mixed with PAMP in combination with liquid nitrogen-treated tumor tissue. The MS-Ap-PAMP adjuvant contributed to the elicitation of a potent systemic Th1 antitumor immunity in vivo., (Copyright © 2013 Wiley Periodicals, Inc.)

The aim of this study was to evaluate the efficacy of suspensions of zinc-containing tricalcium phosphate (TCP) in the healing of thermal burns in rats. β-ZnTCP containing 10 mol % zinc, α-ZnTCP containing 0.9 mol % zinc, and ZnSO4 ·(H2O)7 (ZnSO4) were used. The injections were prepared to suspend ZnSO4 , α-ZnTCP, and β-ZnTCP powders in 2 mL of 1% sodium alginate saline solution containing 2 mg of Zn. In vitro Zn release rates were measured in simulated body fluid. The release of Zn from ZnSO4 was very fast, but that from α-ZnTCP and β-ZnTCP was slowed by transformation to hydroxyapatite. The suspensions were injected into group C (control), D1 (ZnSO4), D2 (α-ZnTCP), and D3 (β-ZnTCP) rats after thermal burns treatment for 3 h. The area under the curve for the plasma Zn for group D1 was the highest, and the order was groups D1 > D2 ≥ D3 ≥ C. The wounded area (Aw) of group D1 had almost the same profile as that of group C, and the Aw at 18 days was about 20%. In contrast, the Aw of group D2 and D3 decreased, and on day 15 was 8% and 37%, respectively. The results indicated that the healing process was shorter in the rats given α-ZnTCP and β-ZnTCP than those given ZnSO4 or the control., (Copyright © 2012 Wiley Periodicals, Inc.)

A silicate-apatite layer was formed on commercially available anodically oxidized titanium rods using Na(2)SiO(3)-containing supersaturated calcium phosphate solutions. With the increase in the concentration of Na(2)SiO(3) in the supersaturated calcium phosphate solutions, the amounts of silicon that precipitated on the titanium rods increased from 0 to 0.07 +/- 0.02 microg/cm(2); meanwhile, the amounts of calcium and phosphorus that precipitated on the titanium rods decreased from 11.6 +/- 1.6 and 5.7 +/- 2.0 microg/cm(2) to 2.6 +/- 0.5 and 3.0 +/- 1.0 microg/cm(2), respectively. The present silicate-apatite composite layers, which demonstrated increased fibroblastic proliferation and osteoblastic proliferation and differentiation in vitro, are promising as coating layers on external fixation pins for decreasing the pin tract infection rate in vivo., ((c) 2009 Wiley Periodicals, Inc.)

In 2004, Shen et al. developed a safe and efficient gene transfer system using a DNA-apatite composite layer. We have recently succeeded in improving further the gene transfer efficiency by immobilizing a cell adhesion molecule laminin, in a DNA-apatite composite layer. In this study, we showed that not only laminin but fibronectin immobilized in a DNA-apatite composite layer enhances cell adhesion and cell spreading on the layer, thereby markedly improving the gene transfer efficiency. Therefore, the immobilization of a cell adhesion molecule in a DNA-apatite composite layer is crucial for improving the gene transfer efficiency. By using fibronectin instead of laminin and optimizing the condition to prepare the fibronectin-DNA-apatite composite layer, the amount (weight) of cell adhesion molecule required was reduced to approximately one-fourth while retaining the relatively high gene transfer efficiency. It was also shown that the resulting fibronectin-DNA-apatite composite layer prepared under the optimized condition mediated the area-specific gene transfer on its surface, that is, DNA was preferentially transferred to the cells adhering to the surface of the fibronectin-DNA-apatite composite layer. The present gene transfer system with potential for area-specific transfection and advantages of safety and relatively high efficiency would be useful in tissue engineering applications, gene therapy, and production of transfection microarrays., ((c) 2009 Wiley Periodicals, Inc.)

A laminin-apatite composite layer with enhanced cell adhesive properties was successfully formed on the surface of an ethylene-vinyl alcohol copolymer (EVOH) by a liquid phase coating process. The coating process was carried out with the following procedure. First, an EVOH plate was alternately dipped in 200 mM calcium and 200 mM phosphate solutions to introduce nuclei or precursors of apatite to its surface. Second, the surface-modified EVOH was immersed in a calcium phosphate solution, which was supersaturated with respect to apatite and containing laminin. As a result of this procedure, a laminin-apatite composite layer with a thickness of 2.5-3.0 microm was formed on the EVOH surface. Epithelial-like cells (BSCC93) adhered to the laminin-apatite composite layer showed enhanced cell spreading, which was due to the biological effect of laminin. The number of cells adhered to the laminin-apatite composite layer on EVOH was approximately 10 times as large as that adhered to the surface of the untreated, laminin-adsorbed, or apatite-coated EVOH. Therefore, this type of composite material consisting of a synthetic polymer, apatite, and laminin has great potential as a skin terminal, with improved adhesiveness to skin tissue, as well as good biocompatibility., (Copyright 2004 Wiley Periodicals, Inc.)

We developed a novel technique to improve tendon-bone attachment by hybridizing calcium phosphate (CaP) with tendons using an alternate soaking process. We characterized the deposited CaP on or in tendons and determined the healing process of anterior cruciate ligament (ACL) grafts by implanting CaP-hybridized free tendons in bone tunnels intra-articularly. Tendons to be implanted were alternately soaked 10 times in a Ca-containing solution and a PO(4)-containing solution for 30 s each. Treated tendons had ash contents threefold that of untreated tendons. Low-crystallinity apatite was found on or in treated tendons. In animal experiments, the CaP-hybridized tendon exhibited osteoclasts at the tendon-bone interface at 5 days after operation. At 2 weeks after operation, there were more osteoclasts and osteoblasts around the tendon than at 5 days after operation. Directly bonded areas were partially found between the implanted tendon and newly formed bone. The formation of a cartilage layer was partially apparent at 3 weeks after operation. The newly formed bone was observed almost around the tendon. We conclude that CaP-hybridized tendons clearly enhance the healing process of ACL grafts at the tendon-bone interface and regenerate a direct insertion-like formation of tendons similar to a normal healthy ACL insertion within 3 weeks after operation., (Copyright 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 319-327, 2004)

The purpose of this study was to evaluate the efficacy of zinc (Zn)-containing beta-tricalcium phosphate (Zn-TCP) in correcting the bone mineral deficiency noted in osteoporosis using ovariectomized rat model. Four rats were used for each of the four experimental groups: D0, D10, D20, and N10. The rats in D0, D10, and D20 groups were ovariectomized, and fed a vitamin D-, Ca-, and Zn-deficient diet, and induced Zn-deficient osteoporoses for 9 weeks. In contrast, the N10 group was the normal rats fed normal healthy diet for 9 weeks. D0 group was injected with pure beta-TCP suspension, D10 and D20 groups were injected with suspensions containing 10 mg of 10 mol % (6.17 wt % Zn) and 20 mol % (12.05 wt % Zn) Zn-TCP, respectively, and the healthy group, N10 were injected with 10 mol %. Zn-TCP suspensions. Injections were administered intramuscularly in the left thigh once a week in all rats, and fed a vitamin D- and Zn-deficient diet for 9 weeks. The plasma calcium (Ca) and Zn levels, plasma alkaline phosphatase activity (ALP) and bone mineral density (BMD) of the lumbar vertebra and femora were measured. The plasma Zn levels in all the rats were between 1.1 and 2.8 microg/mL. The areas under the curves for the Ca, Zn, and ALP (Ca-AUC, Zn-AUC, and ALP-AUC) levels between 0 and 63 days were calculated. Results for the AUCs were as follows: (1) the Zn-AUCs were in the order of N10 = D20 > D10 > D0; (2) the Ca-AUCs for D0, D10 groups were significantly lower than that for the N10 group; (3) the ALP-AUCs for the D10 and D20 groups were significantly higher than that for the N10 group, and that of the D0 group was in between those. The body weight of D10 and D20 groups significantly increased with time, that of the D0 group increased slightly, and that of the N10 group remained unchanged for the entire experimental period. The BMD of the lumbar vertebrae of the D10 and D20 groups (about 100 mg/cm(2)) was significantly higher than that of the D0 group but lower than that of the N10 group. The BMD of the left femur increased more than that of the right femur with the increase in the amount of Zn in the suspension. The results of this study suggest that the local effect on BMD was more pronounced than the effect on the whole body., (Copyright 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 552-560, 2004)