Yohei Jinno

Simvastatin enhances bone formation around titanium implants in rat tibiae

Statins are cholesterol-lowering drugs that have been reported to promote bone formation. The purpose of this study was to investigate the effect of simvastatin on the enhancement of bone formation around titanium implants. Thirty-week-old female rats received pure titanium implants in both tibiae. The animals were intra-peritoneally administered 0, 0.125, 1, 5 or 10 mg kg(-1) of simvastatin daily. After 30 days, the animals were sacrificed, and specimens were prepared. The bone contact ratio of the implant, bone density in the medullary canal and percentage of cortical bone were obtained. Markers for bone turnover were also measured using sera collected at the time of euthanasia. In the medullary canal, a scanty amount of bone was observed in the 0, 0.125 and 1 mg kg(-1) groups. In contrast, in both the 5 and 10 mg kg(-1) groups, thicker bone trabeculae were abundant. Histometric observations showed that the bone contact ratio and the bone density of both groups were significantly greater than those of the other groups (anova, P < 0.01). However, no significant difference in the percentage of cortical bone was found between groups. Serum chemistry showed that statin increased bone formation markers and decreased bone resorption markers. In conclusion, although the dose equivalent to that used in human patients with hypercholesterolemia was not effective, a simvastatin dose of 5 mg kg(-1) or higher increased medullary bone formation around the titanium. In contrast, no effect of simvastatin on pre-existing cortical bone was indicated.

The effect of a single remote injection of statin-impregnated poly (lactic-co-glycolic acid) microspheres on osteogenesis around titanium implants in rat tibia.

The aim of this study was to evaluate the effects of newly developed injectable poly (lactic-co-glycolic acid) (PLGA) microspheres containing fluvastatin on osteogenesis around titanium implants in the rat tibia. After confirmation of the sustained-release profile of fluvastatin from the microspheres by an in vitro assay, the microspheres were administered to the back skin of the rats by a single transdermal injection. At 2 and 4 weeks after the implant surgery, the fluvastatin groups showed enhanced new bone formation around the titanium implants without any influence on the serum biochemistry. In addition, the fluvastatin groups showed increased three-point bending strengths of their femurs. The results of this study indicate that a single remote injection of PLGA/fluvastatin microspheres safely and successfully stimulated bone formation around titanium implants and increased the mechanical properties of bone.

Career choice and future design of dental students in China and Japan

The purpose of this study was to compare career choice and future plans of dental students in China and Japan. Information was derived from a self-answered questionnaire. Significant differences were detected for eight items between the two countries. Regarding motivation towards career choice, 41% of Japanese students indicated positive motives related to helping others, achieving self-worth and health-care related interests, whereas Chinese students indicated that their choice was mainly for financial and prestige reasons, and for 32% of them, dentistry was a passive choice. More Chinese dental students (74%) wanted further education compared with Japanese students (22%). The majority of Japanese students (56.9%) planned to work as general dentists. Conversely, Chinese students were more likely to specialise (50%). More than 50% of Japanese students wanted to work in dental offices, but the majority of Chinese students (65%) preferred university hospital. We found it is strange that nearly one-fourth of the Chinese students did not want to be a clinical dentist mainly because of the poor health-care environment. This study provides a description of the perspectives of Japanese and Chinese dental students and enables a better understanding of career choices and future course design issues.

Vertical bone augmentation with fluvastatin in an injectable delivery system: a rat study

OBJECTIVES HMG-CoA reductase inhibitors (statins) are widely used for hyperlipidemia. Previous studies demonstrate that statins stimulate bone morphogenetic protein-2 (BMP-2) expression and lead to bone formation. The aim of this study was to evaluate whether percutaneously injected statin with a novel statin delivery system achieved vertical bone augmentation. MATERIAL AND METHODS As experimental groups, atelocollagen-alpha-tricalcium phosphate (alphaTCP) composites containing 3.3 mg (low dose) or 6.7 mg (high dose) of fluvastatin were injected (one shot) subcutaneously over the calvarial periosteum of rats. The animals were then sacrificed 1, 2, and 4 weeks after injection. Vertically augmented bone was assessed by histomorphometric procedures, i.e., by measuring new bone thickness (NBT) and bone density (BD). RESULTS In control groups, no newly formed bone could be seen over the calvarial bone. In the experimental groups, in contrast, a large amount of newly formed bone could be seen over the preexisting calvarial bone. The newly formed bone was seen to be in direct contact with the preexisting bone. During the entire observation, significant NBT was observed in the experimental groups (P<0.05). At the final stage of observation (4 weeks), NBT was 66.7% (low-dose group) and 59.7% (high-dose group), while they were from 1% to 16.3% in the control groups. In the experimental groups, BD significantly increased in a time-dependent manner. CONCLUSION Percutaneously applied fluvastatin (one shot) with a composite of alphaTCP and collagen has great potential to augment the height of the bone.

Controlled release of Clarithromycin from PLGA microspheres enhances bone regeneration in rabbit calvaria defects

This study evaluated the sustained release effect of clarithromycin-loaded in PLGA microspheres in a rabbit calvaria defect model. Four bone defects (ø5.0) were created in the calvaria of New Zealand White rabbits (n = 21, n = 7/time point). The defects were randomly designated to four groups. Group 1: No augmentation (sham), Group 2: beta-tricalcium phosphate (β-TCP), Group 3: β-TCP with 0.12 µg clarithromycin, and Group 4: β-TCP with 6.12 µg PLGA microspheres loaded with 0.12 µg Clarithromycin. After 2, 4, and 12 weeks of healing, bone regeneration was evaluated using micro-computed tomography (µCT) and histology. Clarithromycin release from PLGA microspheres revealed sustained release for around 4 weeks with ∼50% release during the first week. Histologically, new bone formation was evident at 2 and 4 weeks of healing in all groups and bone formation increased as a function of healing time. At 12 weeks, Group 4 showed significantly higher amount of newly formed bone compared to Group 1. The µCT showed that Group 4 expressed significantly higher bone formation compared to Group 1 at all time points. The in vivo findings showed that β-TCP with clarithromycin-loaded microspheres can enhance bone formation in bone defects.

Controlled release of clarithromycin from PLGA microspheres enhances bone regeneration in rabbit calvaria defects: CONTROLLED RELEASE OF CLARITHROMYCIN

This study evaluated the sustained release effect of clarithromycin-loaded in PLGA microspheres in a rabbit calvaria defect model. Four bone defects (ø5.0) were created in the calvaria of New Zealand White rabbits (n = 21, n = 7/time point). The defects were randomly designated to four groups. Group 1: No augmentation (sham), Group 2: beta-tricalcium phosphate (β-TCP), Group 3: β-TCP with 0.12 µg clarithromycin, and Group 4: β-TCP with 6.12 µg PLGA microspheres loaded with 0.12 µg Clarithromycin. After 2, 4, and 12 weeks of healing, bone regeneration was evaluated using micro-computed tomography (µCT) and histology. Clarithromycin release from PLGA microspheres revealed sustained release for around 4 weeks with ∼50% release during the first week. Histologically, new bone formation was evident at 2 and 4 weeks of healing in all groups and bone formation increased as a function of healing time. At 12 weeks, Group 4 showed significantly higher amount of newly formed bone compared to Group 1. The µCT showed that Group 4 expressed significantly higher bone formation compared to Group 1 at all time points. The in vivo findings showed that β-TCP with clarithromycin-loaded microspheres can enhance bone formation in bone defects.

Magnesium release from mesoporous carriers on endosseus implants does not influence bone maturation at 6 weeks in rabbit bone

OBJECTIVES The release of magnesium ions (Mg2+ ) from titanium surfaces has been shown to boost the initial biological response of peri-implant bone and to increase the biomechanical strength of osseointegration. The objective of the present paper was to investigate if the initial improvement in osseointegration would influence the bone remodeling also during the maturation stage of bone healing. METHODS Titanium implants were coated with mesoporous titania layers and either loaded with Mg2+ (test group) or left untreated (control group). The implants were inserted in the tibiae of 10 New Zealand White rabbits. Osseointegration was assessed after 6 weeks by means of biomechanical testing (RTQ), non-decalcified histology and histomorphometry (BIC%, BA%, NBA%). The expression of genes involved in the bone formation and remodeling was quantified using qPCR. RESULTS Mg2+ releasing mesoporous titania coatings showed, on average, higher removal torques and histomorphometrical outcomes (RTQ: 17.2 Ncm vs. 15 Ncm; BIC: 38.8% vs. 32.1%; BA%: 71.6% vs. 64%; NBA% 62.5% vs. 54% for the tests vs the controls); however, the differences were not statistically significant. Three osteogenic markers, osteocalcin (OC), collagen 1 alpha 1 (COL1A1), and alkalin phosphatase (ALPL), were respectively 2-fold, 1.53-fold, and 1.13-fold up-regulated in the control group compared to the test. The expression of COL1A1 was particularly high in both groups, while the biomarkers for remodeling and inflammation showed a low expression in both groups. SIGNIFICANCE The results suggested that the initial enhancement in osseointegration induced by magnesium release from mesoporous titania coatings has no detrimental effects during bone maturation.

Implant Vertical Fractures Provoked by Laboratory Procedures: A Finite Element Analysis Inspired from Clinical Cases.

Purpose:To investigate the causes for internal implant fractures, which is suggested to be one of the reasons for marginal bone loss. Materials and Methods:From a 14-year database of 6051 implants, 10 single implant vertical fractures were identified and the abutments were all castable abutments. The abutments presented contamination and irregularities at the internal connecting areas. The hypothesis was that perfect fit was disturbed by laboratory polishing procedures, and finite element analysis (FEA) using overcorrected and undercorrected castable abutment models were created and tested against a perfect fit model. Results:The results from the FEA presented that both overcorrected and undercorrected models presented nonuniform excessive plastic strain distribution in the neck portion of the implants where clinically an implant fracture was noted. Conclusions:The results suggested that laboratory procedures could induce plastic strain of the implant-abutment complex, which increases the risk of fracture.

Tissue Reaction to a Novel Bone Substitute Material Fabricated With Biodegradable Polymer-calcium Phosphate Nanoparticle Composite

Purpose:The aim of this study was to evaluate the effectiveness of a novel bone substitute material fabricated using a biodegradable polymer-calcium phosphate nanoparticle composite. Methods:Porous structured poly-L-lactic acid (PLLA) and hydroxyapatite (HA) nanoparticle composite, which was fabricated using solid-liquid phase separation and freeze-drying methods, was grafted into bone defects created in rat calvarium or tibia. Rats were killed 4 weeks after surgery, and histological analyses were performed to evaluate new bone formation. Results:Scanning electron microscopic observation showed the interconnecting pores within the material and the pore diameter was approximately 100 to 300 &mgr;m. HA nanoparticles were observed to be embedded into the PLLA beams. In the calvarial implantation model, abundant blood vessels and fibroblastic cells were observed penetrating into pores, and in the tibia model, newly formed bone was present around and within the composite. Conclusions:The PLLA-HA nanoparticle composite bone substitute developed in this study showed biocompatibility, elasticity, and operability and thus has potential as a novel bone substitute.

Vertical Bone Augmentation Using Ring Technique with Three Different Materials in the Sheep Mandible Bone

PURPOSE The purpose of this study was to examine the volumetric alterations and osseointegration properties in the augmented area of the ring technique using different types of bone graft material in sheep mandible bone. MATERIALS AND METHODS Three different materials (columnar forms, 7-mm diameter, 3-mm height) were stabilized using dental implants with a turned surface in the mandible bone of Finnish Dorset cross-bred sheep: group A, autogenous bone; group B, bovine bone; group C, biphasic bone substitute. Animals were euthanized after 5 weeks (N = 6). Three-dimensional image data by digital oral scanner were taken at the surgery and sacrifice, and the volume alteration of the material was calculated. The bone samples were fixed in formalin and dehydrated in ethanol. Resin-embedded samples were subjected to non-decalcified ground sectioning, and histologic and histomorphometric analysis (bone and material area alteration, bone-to-implant contact [BIC]) were done. RESULTS In three-dimensional (3D) image analysis, group A showed a statistically higher percentage of remaining materials compared with groups B and C. The histologic observation showed no new bone formations around the implants in all groups, especially at the maxillary site of the implant in the augmented area. In histomorphometric analysis, group A showed a statistically higher percentage of bone area (BA) compared with groups B and C; however, in all groups, bone-to-implant contact (BIC) showed low values, and there were no statistical differences between groups. CONCLUSION The results of this study suggested that the autogenous bone maintained bone volume around the dental implant using the ring technique, and the impact of surface properties was of some importance; osseointegration with the turned surface in the augmented area showed low BIC values in all groups.