Papers by Author: Naoyuki Ochiai

Abstract: Several drug delivery carriers have reported on local delivery of paclitaxel (PTX), but their effects on intraosseous cancer model are not well known. This study was conducted to clarify the therapeutic effects of our newly developed PTX-loaded HAp-alginate composite beads. Cytotoxic activity was assessed on rat’s mammary adenocarcinoma by cell proliferation assay using WST-1 reagent. Antitumor activity was assessed by 8-week-old rat female Fischer 344 rats of metastatic spine cancer. Twenty-three rats were divided into 3 groups: Group 1 (n = 7) and Group 2 (n = 8) was treated with the PTX-loaded HAp-alginate beads using strontium ions and barium ions, respectively. Group 3 (n = 8) was administered with drug-free HAp-alginate beads. We checked disease-free time and survival time among 3 groups. The HAp-alginate beads containing 2.4wt% of PTX showed significant cytotoxic activity on CRL-1666 cells. The effects were decreased with time during 72 h. The animals treated with 2.4wt% of PTX-loaded HAp-alginate beads showed 40% increase in the disease-free time and 25% increase in survival time. Our studies suggest that newly developed HAp-alginate beads can be a candidate carrier of PTX to bone.

Abstract: Unidirectional porous hydroxyapatite (UDPHAp) was developed which has microstructure in that cross sectionally oval pores 100 ~ 300µm in diameter penetrate through the material, and that is suitable for osteogenesis and angiogenesis.The porosity of the UDPHAp was 75 % and the compression strength was 14 MPa. A cortical bone defect was made at proximal tibia of Japanese white rabbit, and a trapezoidal prisms shaped UDPHAp was implanted. By histlogical evaluation, 2 weeks after implantation, new bone and new capillary was observed inside UDPHAp. Twelve weeks after implantation, new bone formation was observed in 41.6 % of the porous area. The results of this study suggest a great possibility of utilizing it in actual clinical setting as a bone substitution.

Abstract: Rigid hydroxyapatite (HAp)-alginate beads were prepared as drug delivery carriers for an anti-cancer drug, paclitaxel (Taxol). Paclitaxel was loaded into the HAp microparticle in process of a spray-drying technique. The HAp-alginate beads including paclitaxel were obtained by a droplet method into barium solution as ionic cross-linkage and dehydration. Cross-sectional analyses indicated the homogeneity of HAp microparticles and barium ions inside the bead. The ratio of alginate to HAp in the beads dominated both mechanical and swelling properties. Drug-release experiment demonstrated the sustained release of paclitaxel from the beads cross-linked with barium ion for 7 days.

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: A FGF-2-apatite composite layer (FGF-AP layer) was formed on the surface of Ti screws in a supersaturated calcium phosphate solution supplemented with FGF-2. By an in vitro study using fibroblastic NIH3T3 cells, it was confirmed that FGF-2 was immobilized in the layer without complete denaturation although the composite layer was formed at 37°C. When Ti screws with the FGF-AP layer were percutaneously implanted in the proximal tibial metaphysis of 16 rabbits, no osteomyelitis was observed in any rabbits although a FGF-2-free AP layer allowed osteomyelitis in some cases in our previous study. These results suggest that a FGF-AP layer formed on Ti screws is useful for resisting bacterial infection during external fixations.

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: A biocompatible glue consisting of human serum albumin (HSA) and citric acid derivative (CAD), named CAD-A glue was developed. CAD was successfully synthesized by the reaction between citric acid and N-hydroxysuccinimide in the presence of 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride. When the CAD-A glue was applied to the collagenbased casings, it took 7 min to obtain half of maximum bonding strength (760 g/cm2). The bonding strength of this glue to collagen-based casings increased with increasing of HSA concentration.The bonding strength of CAD-A glue increased with increasing CAD concentration up to 200 mM, and then decreased with increasing CAD concentration under the fixed HSA concentration (50 w/w%). The CAD-A glue showed excellent wound closure ability rather than fibrin glue when applied to the mouse skin. These results suggested that this developed glue had both tissue compatibility and bonding strength for use in clinical field.

Abstract: Calcium phosphate (CaP) hybridized to a whole tendon graft delayed cell repopulation in anterior cruciate ligament (ACL) reconstruction in rabbits. However, a tendon graft masked with an adhesive tape at the intra-articular (IA) portion to prevent CaP hybridization did not delay cell repopulation. Synovial tissues can adhere to the tendon graft and can invade the tendon graft masked at the IA portion. The masking induced an effect similar to that of the unhybridized tendon graft. The CaP hybridized tendon grafts masked at the IA portion showed cell repopulation 2 weeks earlier than the unmasked CaP hybridized tendon grafts.

Abstract: We hybridized calcium phosphate (CaP) with human semitendinosus and gracilis (ST/G) tendon grafts using an alternate soaking process. To evaluate quantitatively and histologically assess the CaP hybridized human ST/G tendon grafts, we classified them into three groups according to their soaking time – number of soaking cycle: 30 sec – 20 cycles (Group A), 1 min – 15 cycles (Group B), 3 min – 5 cycles (Group C). The tendon grafts were divided into three parts: tibial end (TE), femoral end (FE) and intra-articular (IA) portion. TE was secured using the Krackow technique with No. 2 nonabsorbable sutures, and an Endobutton-CL (Smith & Nephew, USA) was passed through the looped FE, as performed clinically. Then, the IA portion was covered with the sleeve of a rubber glove to prevent CaP hybridization. More soaking cycles induced greater deposition of CaP in the tendon grafts when the total soaking time was the same. Covering the IA portion with a rubber sleeve prevented of CaP deposition. A large amount of CaP in TE was deposited because suture holes increased the total contact area with the solutions.