Papers by Author: Toshiyuki Ikoma

Abstract: Time-controlled releases of proteins from hydroxyapatite/chondroitin sulfate (HAp/ChS) spherical microparticles were achieved by the addition of zinc cation into the mixture solutions of HAp/ChS and protein as a novel formulation. The initial bursts of proteins, such as cytochrome c and bovine serum albumin, were apparently suppressed by the amount of zinc cation, which could be attributed to the formation of coordinate bonds of zinc cation among proteins and/or ChS moleculars. The increase of molecular lengths of ChS chains decreased the adsorbed amount of proteins, which did not apparently affected to the release of proteins.

Abstract: Porous ceramics of hydroxyapatite was fabricated utilizing the crystal growth of thin ice columns parallel to one another in gelatin gel containing hydroxyapatite nanoparticles. The obtained ceramics possessed unidirectional pore channels with a porosity of around 75% and showed compressive strength of up to 13.1 MPa. As control materials, porous hydroxyapatite ceramics with a directionless pore structure were also fabricated by isotropic freezing and compared with the unidirectional samples regarding compressive strength and tissue reaction in vivo. Although the porosity and pore size distribution were similar, the compressive strength and new bone formation ability of the unidirectional samples were significantly greater than those of the random structured porous ceramics.

Abstract: Control of protein release without the initial burst from zinc containing hydroxyapatite porous microparticles (Zn-HAp) was investigated with a novel formulation method. The formulation method was a coat of polyL(L-lactide; PLA) on the microparticle with nano-thickness, which obviously suppressed the initial burst of protein release compared with the microparticles without the formulation, the coat of PLA. The HAp/PLA microparticle with 1-20μm of the size distribution was available for the drug delivery carrier of proteins without the degradation.

Abstract: The extent of osseous involvement, particularly spinal cord compression, is directly correlated with patient survival. To treat metastatic spine cancer, we have developed novel paclitaxel-loaded hydroxyapatite-alginate gels. In this study, an intraosseous spinal cancer model in rats was used to investigate the efficacy of local treatment. Ten rats were randomized into two groups, a local treatment group and a control group. Disease-free time and survival rate in the local treatment group were significantly longer in this model. (p<0.05)

Abstract: Homogeneous nano-thin layer of hydroxyapatite (HAp) nanocrystals on the gold surface was fabricated by an electrophoretic deposition method (EPD); the HAp nanocrystals were dispersed into ethanol and the applied voltage was varied. The HAp nanocrystals were prepared by a wet method at 4 °C and 80 °C, which were characterized by X-ray diffraction and Fourier-transform infrared spectroscopy. The micro-thin layer of HAp nanocrystals was initially formed, and the ultrasonic treatments can remove the surplus nanocrystals from the surface. The nanostructure of the surface was investigated by atomic force microscopy and contact angle measurement. The thickness of coating layers was approximately 20nm and the root mean square (RMS) roughness was under 6.6 nm, which was clearly depended on the crystal sizes, applied voltages and applied times.

Abstract: Calcium phosphate (Ca-P) biomaterials have been proved to show osteoinductivity, however the affecting factors and mechanism are still unclear now. In this study, the surface characteristics of biphasic Ca-P ceramics (hydroxyapatite/tricalcium phosphate; HA/TCP) sintered at the distinct temperature were investigated and the mechanism of the osteoinductivity was discussed. The osteoinductivity of HA/TCP ceramics increased with decreasing the sintering temperature. The different surface micro-structure resulted from different sintering temperature includes phase composition, surface micro-structure, and surface potential. These characteristics should be the important factors affecting osteoinductivity.

Abstract: Hydroxyapatite/hyaluronic acid (HAp/HyA) and hydroxyapatite/chondroitin sulfate (HAp/ChS) microparticles, which show the high adsorption ability of proteins, high biocompatibility and osteoconductivity, are potential scaffolds for a time-controlled BMP release. The present study evaluated the biocompatibility and osteoconductivity of the composites after injection into bone defect. Drilled bone holes were made at tibia and femur of Japanese white rabbits, and HAp/HyA or HAp/ChS was implanted into each bone hole using an injection syringe. After 2 and 4 weeks of implantation, rabbits were sacrificed and histological observations were conducted with HE, TRAP, and ALP staining. Histological observations revealed that HAp/ChS has superior biocompatibility compared with HAp/HyA, and 20% HAp/ChS promotes bone formation as well as osteoblast activities compared with lower ratios of HAp/ChS.

Abstract: Silk fibroin (SF) films containing 5wt% of CaCl2 were prepared by a cast-film method from the degummed SF and then immersed into the simulated body fluid (SBF) to deposit hydroxyapatite (HAp) crystals. The multilayer film of HAp and SF (5-layers), and pure SF film (4-layers) were prepared by a thermo-compression method at 130 °C and 3MPa for 4min. The ratio of β-sheet structure against other structures in both samples showed almost same value of 55.8% and 55.1%. The swelling ratio and in vitro biodegradation were examined by incubating in phosphate-buffered saline (PBS) with and without protease XIV for 1 to 14 days. The changes of sample weight and its tensile strength were investigated. The multilayer film showed slower biodegradation and higher mechanical strength compared with pure SF film.

Abstract: Hydroxyapatite/chondroitin sulfate (HAp/ChS) microparticles with the perfectly spherical shape and the averaged particle sizes of 4.1, 7.8, 19.9 and 29.4 µm were fabricated by a spray dry method under the different atomizing pressures and the concentrations of suspensions. The contents of ChS in the microparticles were varied at 1.49, 3.18, 7.82, 14.2 wt%, and the ChS elution rate in distilled water from the microparticles was increased with the increase of ChS contents. The adsorption isotherms of cytochrome C on the microparticles in 1/10 diluted phosphate buffer saline (PBS) were followed to the Langmuir’s equation regardless of the change of ChS contents, while those of catalase were not followed. The HAp/ChS microparticles can adsorb greater amount of cytochrome C than pure HAp microparticles, but less amount of catalase than pure HAp. The electrostatic interaction between the proteins and ChS was of great importance in the adsorption properties.

Abstract: Hydroxyapatite/collagen (HAp/Col) composite scaffold with unidirectionally elongated pores (scaffold-U) was fabricated by the unidirectional solidification with ice growth and subsequent freeze-dry process. The pore architecture in the composite was evaluated by using scanning electron microscopy (SEM) and micro computed tomography (micro-CT) with a high resolution. The SEM observation showed that the scaffold-U had unidirectional pores elongated along the vertical direction (i.e. ice growth direction), however the horizontal cross-section showed quite different pore morphology: spindle-shaped pores with random direction. The 3-D micro-CT image of the scaffold-U simultaneously showed the microstructure of the unidirectionally elongated pore and the cross-sectional pore, indicating that the interconnected micropores were successfully fabricated along the ice growth direction. The micro-CT is a powerful tool for the visualization of 3-D pore structure.