Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Yasunori AYUKAWA Last modified date:2021.06.28

Professor / Division of Oral Rehabilitation / Department of Dental Science / Faculty of Dental Science


Papers
1. Naomi Adachi, Yasunori Ayukawa, Noriyuki Yasunami, Akihiro Furuhashi, Mikio Imai, Koma Sanda, Ikiru Atsuta, Kiyoshi Koyano, Preventive effect of fluvastatin on the development of medication-related osteonecrosis of the jaw, Scientific reports, 10.1038/s41598-020-61724-6, 10, 1, 2020.12, Medication-related osteonecrosis of the jaw (MRONJ) occurs in patients undergoing oral surgery while medicated with bisphosphonate, denosumab or anti-angiogenic agents. We employed a MRONJ-like rat model to investigate whether injecting fluvastatin at extraction sites prevents MRONJ-like lesion. A MRONJ-like model was created by treating rats with zoledronate and dexamethasone, extracting teeth, and immediately injecting fluvastatin at the extraction site. The experimental group comprised three subgroups treated with low (0.1 mg/kg; FS-L), medium (1.0 mg/kg; FS-M) and high concentrations (10 mg/kg; FS-H) of fluvastatin. Necrotic bone exposure was significantly lower in the FS-M (p = 0.028) and FS-H (p = 0.041) groups than in the MRONJ group. The distance between the edges of the epithelial surfaces was significantly shorter in the FS-M (p = 0.042) and FS-H (p = 0.041) groups. The area of necrotic bone and the necrotic bone ratio were significantly smaller in the FS-H group (p = 0.041 and p = 0.042 respectively). Bone volume fraction calculated on μ-CT images was significantly larger in the FS-H group than in the MRONJ group (p = 0.021). Our findings suggest that a single local injection of fluvastatin following tooth extraction can potentially reduce the chance of developing MRONJ-like lesion in rats..
2. Chika Arimizu, Yasunori Ayukawa, Rika Kuwatsuru, Satoru Haresaku, Yasuyuki Matsushita, Kiyoshi Koyano, Factors associated with discontinuation and resumption of implant maintenance therapy, Journal of Oral Science, 10.2334/josnusd.19-0318, 62, 4, 356-359, 2020.09, Discontinuation of implant maintenance is the main risk factor for implant failure. The purpose of this study was to identify factors associated with previous discontinuation and resumption of maintenance among implant patients. A questionnaire survey was sent to 171 patients receiving implant maintenance at a university hospital; 169 patients responded. To assess the effect of job status, 26 patients (15.4%) with a history of maintenance discontinuation were classified as employed and nonemployed. The main reasons for previously discontinuing maintenance were work issues (in employed respondents) and dissatisfaction with treatment skill or chairside manner (in nonemployed respondents). The main reasons for resuming maintenance were those related to dental treatment (in employed respondents) and awareness of the importance of maintenance (in nonemployed respondents). There were significant differences in relation to job status in the reasons reported for discontinuing and resuming maintenance (both P < 0.05). The present findings suggest that oral health professionals should consider these factors when assisting patients in reducing the risk of implant failure..
3. Jiangqi Hu, Ikiru Atsuta, Yasunori Ayukawa, Xudiyang Zhou, Yunia Dwi Rakhmatia, Kiyoshi Koyano, The impact of surface alteration on epithelial tissue attachment after the mechanical cleaning of titanium or zirconia surface, Journal of oral rehabilitation, 10.1111/joor.12920, 47, 9, 1065-1076, 2020.09, Objective: Mechanical plaque removal may alter the surface morphology of the gingival penetration part of the implant. We applied an air-powered abrasive system (AP), titanium curette (TC), stainless curette (SC), ultrasound scaler (US), and titanium brush (TB) which are commonly used to remove plaque, to titanium or zirconia and the changes in surface morphology and the epithelial attach against substrata. Materials and Methods: (a) The morphological changes of titanium and zirconia after mechanical cleaning were assessed by scanning electron microscopy and a roughness analyser. (b) Oral epithelial cells of rats were inoculated on the surface of the materials after mechanical cleaning, and the adherence of epithelial cells was observed. (c) The maxillary first molars were extracted from the rats and replaced by experimental titanium or zirconia implants. The length of the immunoreactive laminin-332 band was observed at the implant-peri-implant epithelium interface. Results: (a) The surface roughness increased in experimental groups except the AP group. (b) Among the experimental groups, the AP group showed the highest number of attached cells. (c) The length of the immunoreactive laminin-332 band was longer in the control group than those in all five experimental groups. Among the experimental groups, the AP group showed the longest band. Conclusion: All mechanical cleaning methods increased the surface roughness of the materials except AP. AP did not cause distinct implant surface alterations. Surface alteration caused by mechanical cleaning may evoke inferior for epithelial attachment and reduce resistance against foreign infiltration..
4. Takuya Haraguchi, Yasunori Ayukawa, Yukie Shibata, Toru Takeshita, Ikiru Atsuta, Yoichiro Ogino, Noriyuki Yasunami, Yoshihisa Yamashita, Kiyoshi Koyano, Effect of Calcium Chloride Hydrothermal Treatment of Titanium on Protein, Cellular, and Bacterial Adhesion Properties, Journal of Clinical Medicine, 10.3390/jcm9082627, 9, 8, 2020.08, Topographical modification of the dental implant surface is one of the main topics for the improvement of the material, however, the roughened surface has some risks for peri-implantitis. A hydrothermal treatment (HT) of titanium with calcium chloride solution was reported to improve osseointegration and soft tissue sealing without changing the surface topography; however, its mechanism is unclear. We herewith investigated the interaction between extracellular matrix (ECM) protein and HT titanium. Furthermore, we also clarified the bacterial interaction. We employed two kinds of HT, HT with water (DW-HT) and HT with calcium chloride solution (Ca-HT). As a result, the adsorptions of both laminin-332 and osteopontin onto the Ca-HT surface were enhanced. In contrast, the adsorption of albumin, which was reported to have no cell adhesion capacity, was not influenced by Ca-HT. Osteoblast adhesion onto Ca-HT was also enhanced. Although Ca-HT was reported to enhance both epithelial cell attachment strength and in vivo peri-implant epithelial bonding, the number of epithelial cell attachment was not increased even after HT. Ca-HT had no impact in the adhesion of Streptococcus gordonii. These results suggest that Ca-HT enhances cell adhesion onto titanium without increasing bacterial adhesion, and the improvement of ECM protein adsorption is supposed to contribute to cell adhesion..
5. Jiangqi Hu, Ikiru Atsuta, Yasunori Ayukawa, Tianren Zhou, Ikue Narimatsu, Kiyoshi Koyano, Effect of titanium or zirconia implant abutments on epithelial attachments after ultrasonic cleaning, Journal of Oral Science, 10.2334/josnusd.19-0332, 62, 3, 331-334, 2020.07, Zirconia is widely employed as a material during dental implant work because of its superior esthetics. This study sought to evaluate the impact of titanium or zirconia implant abutments on epithelial attachments after ultrasonic cleaning. These implants were inserted into the extraction socket of rat maxillary first molars. Then, the length of the horseradish per-oxidase (HRP) reaction was measured. In addition, titanium and zirconia disks were cleaned using an ultrasonic scaler, surface morphology changes were observed, and the number of epithelial cell attachments to the surface was measured. Ultimately, the surfaces of the titanium disks were easier to damage than those of the zirconia ones. There was no difference in the number of epithelial cell attachments between the two materials with the ultrasonic cleaning. The length of the HRP reaction was shorter on the zirconia implant abutment surface than on the titanium one after mechanical cleaning. In conclusion, zirconia is harder than titanium and a better choice for use in the epithelial tissue attachment. Zirconia is more suitable as a material for implant abutments than titanium..
6. Xudiyang Zhou, Ikiru Atsuta, Yasunori Ayukawa, Ikue Narimatsu, Tianren Zhou, Jiangqi Hu, Kiyoshi Koyano, Effects of different divalent cation hydrothermal treatments of titanium implant surfaces for epithelial tissue sealing, Materials, 10.3390/MA13092038, 13, 9, 2020.05, The improvement of peri-implant epithelium (PIE) adhesion to titanium (Ti) may promote Ti dental implant stability. This study aims to investigate whether there is a positive effect of Ti hydrothermally treated (HT) with calcium chloride (CaCl2), zinc chloride (ZnCl2), and strontium chloride (SrCl2) on promoting PIE sealing. We analyzed the response of a rat oral epithelial cell (OEC) culture and performed an in vivo study in which the maxillary right first molars of rats were extracted and replaced with calcium (Ca)-HT, zinc (Zn)-HT, strontium (Sr)-HT, or non-treated control (Cont) implants. The OEC adhesion on Ca-HT and Zn-HT Ti plates had a higher expression of adhesion proteins than cells on the Cont and Sr-HT Ti plates. Additionally, the implant PIE of the Ca-HT and Zn-HT groups revealed better expression of immunoreactive laminin-332 (Ln-322) at 2 weeks after implantation. The Ca-HT and Zn-HT groups also showed better attachment at the implant-PIE interface, which inhibited horseradish peroxidase penetration. These results demonstrated that the divalent cations of Ca (Ca2+) and Zn (Zn2+)-HT improve the integration of epithelium around the implant, which may facilitate the creation of a soft barrier around the implant to protect it from foreign body penetration..
7. Kenji Maekawa, Tomoko Ikeuchi, Shoji Shinkai, Hirohiko Hirano, Masahiro Ryu, Katsushi Tamaki, Hirofumi Yatani, Takuo Kuboki, Aya Kimura-Ono, Takeshi Kikutani, Takashi Suganuma, Yasunori Ayukawa, Tomoya Gonda, Toru Ogawa, Masanori Fujisawa, Shoichi Ishigaki, Yutaka Watanabe, Akihiko Kitamura, Yu Taniguchi, Yoshinori Fujiwara, Ayako Edahiro, Yuki Ohara, Junichi Furuya, Junko Nakajima, Kento Umeki, Kentaro Igarashi, Yasuhiro Horibe, Yoshihiro Kugimiya, Yasuhiko Kawai, Hideo Matsumura, Tetsuo Ichikawa, Shuji Ohkawa, Number of functional teeth more strongly predicts all-cause mortality than number of present teeth in Japanese older adults, Geriatrics and Gerontology International, 10.1111/ggi.13911, 2020.01, Aim: Previous studies on the association between intraoral conditions and mortality in community-dwelling older individuals reported that fewer present teeth (PT) are significant risk factors for mortality. However, how the number of PT relative to the number of functional teeth (FT), including both present and rehabilitated teeth, influences mortality has not been investigated fully. This study examined the impact of the number of FT on mortality among community-dwelling Japanese older adults. Methods: This study was a retrospective, observational and population-based follow-up study, which examined 1188 older individuals who participated in an annual geriatric health examination from 2009 to 2015. The average follow-up period was 1697.0 ± 774.5 days. The primary outcome was all-cause mortality at follow-up. The numbers of PT and FT of each participant were counted during an oral examination. In addition, demographics, clinical variables, blood nutrient markers, physical functions and perceived masticatory function were measured. Results: Kaplan–Meier analysis, followed by a log-rank test, revealed that fewer PT (P < 0.001) and FT (P = 0.002) were significantly associated with a reduced survival rate. Cox's proportional hazard analysis indicated that the number of FT, but not the number of PT, was a significant independent mortality risk factor after adjusting for demographics, clinical variables, nutrient markers and physical functioning (P = 0.036, hazard ratio: 2.089). Conclusions: Current results suggest that the number of FT more strongly predicts all-cause mortality than the number of PT among community-dwelling older adults. Further studies are necessary to consider the confounding of socioeconomic status and disability status. Geriatr Gerontol Int 2020; ••: ••–••..
8. Nobuyuki Ueda, Ikiru Atsuta, Yasunori Ayukawa, Takayoshi Yamaza, Akihiro Furuhashi, Ikue Narimatsu, Yuri Matsuura, Ryosuke Kondo, Yu Watanabe, Xiaoxu Zhang, Kiyoshi Koyano, Novel application method for mesenchymal stem cell therapy utilizing its attractant-responsive accumulation property, Applied Sciences (Switzerland), 10.3390/app9224908, 9, 22, 2019.11, Stem cell therapy is an emerging treatment modality for various diseases. Because mesenchymal stem cells (MSCs) are known to accumulate at the site of damage, their possible clinical application has been investigated. MSCs are usually administered using intravenous injection, but this route carries a risk of pulmonary embolism. In contrast, topical injection of MSCs reportedly has an inferior therapeutic effect. We developed a remote administration method that uses collagen gel as a scaffold and investigated the effect of this scaffold on the retention of stemness, homing ability, and therapeutic effect using a mouse tooth extraction model. After verifying the retention of stemness of MSCs isolated from the bone marrow of donor mice in the scaffold, we administered MSCs subcutaneously into the back of the recipient mice with scaffold and observed the accumulation and the acceleration of healing of the extraction socket of the maxillary first molar. The MSCs cultured with scaffold retained stemness, the MSCs injected into back skin with scaffold successfully accumulated around the extraction socket, and socket healing was significantly enhanced. In conclusion, administration of MSCs with collagen scaffold at a remote site enhanced the lesion healing without the drawbacks of currently used administration methods..
9. Tatsuya Matsuzaki, Yasunori Ayukawa, Yasuyuki Matsushita, Nobuo Sakai, Maki Matsuzaki, Tomohiro Masuzaki, Takuya Haraguchi, Yoichiro Ogino, Kiyoshi Koyano, Effect of post-osseointegration loading magnitude on the dynamics of peri-implant bone
a finite element analysis and in vivo study, Journal of Prosthodontic Research, 10.1016/j.jpor.2018.10.009, 63, 4, 453-459, 2019.10, Purpose: Much research has been invested in determining the effects of postoperative loading of implants and whether this loading contributes to implant failure, but the issue remains controversial. The present study aimed to elucidate whether cyclic lateral loading of an implant causes bone resorption or bone formation at various loading magnitudes, using a finite element method (FEM) and peri-implant morphologic and morphometric analyses. Methods: An FEM model was created using Digital Imaging and Communications in Medicine (DICOM) data of rabbit tibia. For the animal study, implants were inserted into rabbit tibia and, after osseointegration, were subjected to lateral cyclic loading of 20N, 40N or 60N. Results: Bone-implant contact was significantly higher in both 40N and 60N groups. Bone–abutment contact (BAC) was extraordinarily observed in all experimental groups. Bone height was higher than the implant platform level at higher levels of loading (60 N). Among the three experimental groups, those receiving 40 N loading had the highest bone height and BAC. Larger BAC values were observed on the compressive side than the tensile side. Conclusions: Peri-implant bone formation was enhanced with increased loading, with bone formation predominantly on the compressive side. BAC was highest in the 40 N group, implying existence of a loading threshold for peri-implant bone formation and resorption..
10. Tianren Zhou, Yasuko Moriyama, Yasunori Ayukawa, Yunia Dwi Rakhmatia, Xudiyang Zhou, Jiangqi Hu, Kiyoshi Koyano, Injectable Porous Bioresorbable Composite Containing Fluvastatin for Bone Augmentation, ACS Biomaterials Science and Engineering, 10.1021/acsbiomaterials.9b01045, 5, 10, 5422-5429, 2019.10, The purpose of this study was to evaluate the effects of an injectable composite made up of calcium sulfate (CAS), fluvastatin (FS), and atelocollagen on bone augmentation in rats. Porous structures and compressive strength of composites were evaluated. The cumulative release kinetics of FS were determined in vitro by a spectrophotometer. To observe bone regeneration in vivo, five different materials (normal saline; atelocollagen gel only; composite of CAS and atelocollagen; composite containing 0.5% FS; and composite containing 1.0% FS) were injected in extraction sockets and in the crania of rats. Microcomputed tomography and histological evaluation were performed after 2, 4, and 8 weeks of healing time. The composites had high porosity (greater than 55%). FS kept a slow and stable release for >30 days. In vivo results demonstrated that more new bone was formed in the FS groups compared with the other groups, and both bone mass and bone density had prominent increase in maxillae and crania. Resorption of the composite was also observed for cranial tissues. In conclusion, this composite can be applied percutaneously, without any incision. It has excellent properties with replaceability into bone and anabolic effects for bone formation, as well as a drug delivery system for bone formation..
11. Yasunori Ayukawa, Wakana Oshiro, Ikiru Atsuta, Akihiro Furuhashi, Ryosuke Kondo, Yohei Jinno, Kiyoshi Koyano, Long Term Retention of Gingival Sealing around Titanium Implants with CaCl2 Hydrothermal Treatment
A Rodent Study, Journal of Clinical Medicine, 10.3390/jcm8101560, 8, 10, 2019.09, We previously reported that CaCl2 hydrothermal-treated (Ca-HT) titanium (Ti) implants induced a tight sealing at the interface between the implant and peri-implant epithelium (PIE) after implantation. However, it is not clear how long this improved epithelium sealing can be maintained. We subsequently investigated whether the positive effect of Ca-HT to promote sealing between the PIE and implant was sustained longer term. Maxillary molars were extracted from rats and replaced with either Ca-HT implants (Ca-HT group), distilled water-HT implants (DW-HT group) or non-treated implants (control group). After 16 weeks, the majority of implants in the Ca-HT group remained at the maxillary with no apical extension of the PIE. Conversely, half the number of control implants was lost following down-growth of the PIE. The effect of Ca-HT on migration and proliferation of rat oral epithelial cells (OECs) was also investigated. In OECs cultured on Ca-HT Ti plates, protein expression in relation to cell migration decreased, and proliferation was higher than other groups. Surface analysis indicated HT enhanced the formation of surface TiO2 layer without altering surface topography. Consequently, Ca-HT of Ti reduced PIE down-growth via tight epithelial attachment to the surface, which may enhance implant capability for a longer time post-implantation..
12. Yoko Takemura, Yasuko Moriyama, Yasunori Ayukawa, Kosaku Kurata, Yunia D. Rakhmatia, Kiyoshi Koyano, Mechanical loading induced osteocyte apoptosis and connexin 43 expression in three-dimensional cell culture and dental implant model, Journal of Biomedical Materials Research - Part A, 10.1002/jbm.a.36597, 107, 4, 815-827, 2019.04, Osteocytes are thought to act as stress sensors, and are known to display a gap junction-mediated stress-transfer mechanism. To demonstrate the stress-related function of osteocytes, cells of an osteocyte-like cell line derived from murine long bone osteocyte Y4 (MLO-Y4) were cultivated in a three-dimensional culture and subjected to cyclic loading from a titanium plate. This application of physiological loading using a titanium plate significantly increased connexin 43 (Cx43) expression, the number of dead and apoptotic cells, and receptor activator of nuclear factor κB ligand expression. Furthermore, the conditioned medium from the loaded osteocytes induced alkaline phosphatase activity in bone marrow cell culture. In addition, we immunohistologically determined whether bone metabolism increased as a result of the occlusal force in the bone surrounding the titanium implants in a rat model. Increased Cx43 expression and apoptotic osteocytes were observed in the loading group as well as a significantly increased number of tartrate-resistant acid phosphatase-positive cells. These findings indicate that stress from the implant adversely affected the osteocytes, which may promote osteoclastic and osteoblastic cell formation around the implants..
13. Mikio Imai, Yasunori Ayukawa, Noriyuki Yasunami, Akihiro Furuhashi, Yoko Takemura, Naomi Adachi, Jiangqi Hu, Xudiyang Zhou, Yasuko Moriyama, Atsuta Ikiru, Kosaku Kurata, Kiyoshi Koyano, Effect of a Single Injection of Benidipine-Impregnated Biodegradable Microcarriers on Bone and Gingival Healing at the Tooth Extraction Socket, Advances in Wound Care, 10.1089/wound.2018.0834, 8, 3, 108-117, 2019.03, Objective: A dihydropyridine-type calcium channel blocker, benidipine (BD), is extensively used in hypertension therapy. In vitro study reported BD promoting bone metabolism. We evaluated the effect of sustained release of BD-loaded poly(lactic-co-glycolic acid) (PLGA) microcarriers on the promotion of bone and gingival healing at an extraction socket in vivo. In addition, the effect of BD on osteoblasts, osteocytes, fibroblasts, and epithelial cells was evaluated in vitro. Approach: The maxillary first molar of rats was extracted. Next, PLGA microcarriers containing BD were directly injected into the gingivobuccal fold as a single dose. After injection, bone and soft-tissue healing was histologically evaluated. Effect of BD on proliferation, migration, and gene expression of gingival and bone cell was also examined in vitro. Results: After tooth extraction, BD significantly augmented bone volume and density, and also epithelial wound healing. During in vitro studies, BD promoted significant proliferation and migration of fibroblasts and epithelial cells. Real-time RT-PCR revealed that BD upregulated messenger RNA expression of Ahsg (alpha 2-HS glycoprotein) and Csf2 (colony-stimulating factor 2) in osteoblasts. Innovation: The prevention of bone and soft-tissue reduction associated with tooth extraction has been eagerly anticipated in the field of dentistry. This study first reported the effect of BD on extraction socket healing. Conclusion: A single dose of topically administered BD-loaded PLGA microcarriers promoted bone and soft-tissue healing at the extraction site of tooth..
14. Atsuta Ikiru, Yasunori Ayukawa, Akihiro Furuhashi, Ikue Narimatsu, Ryosuke Kondo, Wakana Oshiro, Kiyoshi Koyano, Epithelial sealing effectiveness against titanium or zirconia implants surface, Journal of Biomedical Materials Research - Part A, 10.1002/jbm.a.36651, 2019.01, The aims of implant treatment now involve not only restoration of mastication function, but also recovery of esthetics. Currently, zirconia is widely used as an esthetic material for implant abutment. Therefore, it is very important to understand the efficacy of zirconia for epithelial sealing as an implant material. We compared the effects of materials on the sealing of the peri-implant epithelium (PIE) to titanium (Ti) or zirconia (Zr) implants, for application to clinical work. Maxillary first molars were extracted from rats and replaced with Ti or Zr implants. The sealing of the PIE to the implants was evaluated with immunohistochemistry observation and HRP analysis. The morphological and functional changes in rat oral epithelial cells (OECs) cultured on Ti or Zr plates were also evaluated. After 4 weeks, the PIE on the Ti and Zr implants showed similar structures. The Zr implants appeared to form a weak epithelial seal at the tissue–implant interface, and exhibited markedly less adhesive structures than the Ti implants under electron microscopic observation. In the in vitro experiments, decreased expression levels of adhesion proteins were observed in OECs cultured on Zr plates compared with those cultured on Ti plates. In addition, the cell adherence on Zr plates was reduced, while the cell migration was low on Ti plates. Zr is a better choice for an esthetic implant material, but needs further improvement for integration with the epithelial wound healing process around a dental implant..
15. Haomiao Zhang, Yasuko Moriyama, Yasunori Ayukawa, Yunia Dwi Rakhmatia, Yoko Takemura, Noriyuki Yasunami, Kiyoshi Koyano, Generation and histomorphometric evaluation of a novel fluvastatin-containing poly(lactic-co-glycolic acid) membrane for guided bone regeneration, Odontology, 10.1007/s10266-018-0376-z, 107, 1, 37-45, 2019.01, The purpose of this study was to evaluate the effects of a poly(lactic-co-glycolic acid) (PLGA) membrane containing fluvastatin on bone regeneration at bone defects in rat calvaria and tibia for possible use as a guided bone regeneration (GBR) membrane. PLGA and fluvastatin-containing PLGA (PLGA–fluvastatin) membranes were prepared and mechanical properties were evaluated. Standardized bony defects were created in rat calvaria and the right tibia, and covered with a PLGA or PLGA–fluvastatin membrane. Bone regeneration was evaluated using image analysis based on histologic examination. At 4 and 8 weeks after membrane implantation, the PLGA–fluvastatin group displayed enhanced new bone formation around the edge of the defect compared with the PLGA membrane group in the calvarial model. Thick bone regeneration was observed in tibia-defect sites in the PLGA–fluvastatin membrane group. These results suggest that the PLGA-containing fluvastatin membrane prepared in this study may potentially be used as a GBR membrane..
16. Yasushige Sakamoto, Yasunori Ayukawa, Akihiro Furuhashi, Michimasa Kamo, Junji Ikeda, Ikiru Atsuta, Takuya Haraguchi, Kiyoshi Koyano, Effect of hydrothermal treatment with distilled water on titanium alloy for epithelial cellular attachment, Materials, 10.3390/ma12172748, 12, 7, 2019.01, The enhancement of oral epithelial adhesion to the trans-mucosal material of dental implants may improve their long-term stability. The aim of this study is to investigate whether hydrothermal treatment with distilled water (HT-DW) applied to a Ti-6Al-4V (Ti64) alloy could improve epithelial cellular attachment. We hypothesized that this treatment would enhance the adsorption of proteins and the adhesion of gingival epithelial GE1 cells. This treatment changed the surface crystal structure into an anatase type of titanium oxide without an apparent change of surface roughness or topography. Nitrogen was not detected on the HT-DW-treated Ti64, which indicates decontamination. HT-DW-treated Ti64 exhibited a hydrophilic surface with a less than 10° angle of water contact. Adsorption of laminin-332 to the HT-DW-treated Ti64 was significantly greater than that of the untreated Ti64 plates (64). The number of GE1 cells on the HT-DW-treated Ti64 at 1 and 3 days was significantly lower than that on 64; however, cell adhesion strength on HT-DW was greater, with a higher expression of integrin β 4, compared with 64. This indicates that the HT-DW treatment of Ti64 improves the integration of GE1 cells, which might facilitate the development of a soft tissue barrier around the implant..
17. Ikue Narimatsu, Ikiru Atsuta, Yasunori Ayukawa, Wakana Oshiro, Noriyuki Yasunami, Akihiro Furuhashi, Kiyoshi Koyano, Epithelial and Connective Tissue Sealing around Titanium Implants with Various Typical Surface Finishes, ACS Biomaterials Science and Engineering, 10.1021/acsbiomaterials.9b00499, 2019.01, Soft tissue barrier around a dental implant plays a crucial role in the success of dental implants because it protects underlying hard tissue structures. A number of surface alteration procedures of implants have been introduced to improve bone-implant contact, but there has been little research on the peri-implant soft tissue (PIS) seal. The present study focuses on the "biologic width" of epithelial and connective tissue seals around implants with various typical surface finishes by testing surfaces that have been machined (Ms), roughened by sandblasting and acid etching (Rs), treated hydrothermally with CaCl2 (Cs), or anodized (As). Ms, Rs, and As techniques are commonly used to finish surfaces of commercially available dental implants. The Cs technique was reported to produce strong epithelial cell-titanium adhesion. For culture study, rat oral epithelial cells (OECs) and fibroblasts were cultured on Ms, Rs, Cs, and As titanium plates. There was less cell adherence of OECs and more collagen expression when cultured on Rs and As plates than when cultured on Ms and Cs plates. For the in vivo study, implants with Ms, Rs, Cs, and As surfaces were placed in the rats' oral cavity. Although the PIS structure was similar to that around natural teeth, a horseradish peroxide assay revealed that the sealing ability around the Ms and Rs implants was weaker than that around Cs implants. After 16 weeks, Rs implants exhibited peri-implant epithelial apical down-growth and had lost bone support. Thus, although a smooth surface (Ms and Cs) showed better epithelial attachment, rough surfaces (Rs and As) are more suitable for binding to the connective tissue. Strong epithelium-implant attachment seems to be a fundamental defense against foreign body penetration. Selecting suitable surfaces to ensure strong sealing is important for implant success..
18. Rei Nagao, Daisuke Esaki, Yukie Shibata, Satoshi Ikawa, Katsuhisa Kitano, Yasunori Ayukawa, Yasuyuki Matsushita, Toru Takeshita, Yoshihisa Yamashita, Masaaki Matsuzaki, Kiyoshi Koyano, Investigation of a novel sterilization method for biofilms formed on titanium surfaces, dental materials journal, 10.4012/dmj.2018-274, 38, 4, 654-662, 2019.01, The development of effective methods to disinfect biofilms on dental materials is medically important. This study evaluated the bactericidal effects of peroxynitric acid (HOONO2; PNA) on biofilms formed on titanium surfaces. Streptococcus gordonii was cultured on either machined or rough titanium discs that were then used to evaluate the bactericidal effects of seven reagents, i.e., normal saline, benzalkonium chloride disinfectant solution, chlorhexidine digluconate solution, three concentration types of PNA, and inactivated PNA. Using low concentration of PNA, the bacterial count based on a CFU assay reached an undetectable level within 10 s; this bactericidal effect was the strongest observed for the seven tested reagents. Thus, PNA may be more useful than other disinfectants for sterilizing biofilms on titanium surfaces that have been contaminated with bacteria..
19. Yunia Dwi Rakhmatia, Yasunori Ayukawa, Akihiro Furuhashi, Kiyoshi Koyano, Carbonate apatite containing statin enhances bone formation in healing incisal extraction sockets in rats, Materials, 10.3390/ma11071201, 11, 7, 2018.07, The purpose of this study was to evaluate the feasibility of using apatite blocks fabricated by a dissolution-precipitation reaction of preset gypsum, with or without statin, to enhance bone formation during socket healing after tooth extraction. Preset gypsum blocks were immersed in a Na3PO4 aqueous solution to make hydroxyapatite (HA) low crystalline and HA containing statin (HAFS), or in a mixed solution of Na2HPO4 and NaHCO3 to make carbonate apatite (CO) and CO containing statin (COFS). The right mandibular incisors of four-week-old male Wistar rats were extracted and the sockets were filled with one of the bone substitutes or left untreated as a control (C). The animals were sacrificed at two and four weeks. Areas in the healing socket were evaluated by micro-computed tomography (micro-CT) and histological analyses. The bone volume, trabecular thickness, and trabecular separation were greatest in the COFS group, followed by the CO, HAFS, HA, and C groups. The bone mineral density of the COFS group was greater than that of the other groups when evaluated in the vertical plane. The results of this study suggest that COFS not only allowed, but also promoted, bone healing in the socket. This finding could be applicable for alveolar bone preservation after tooth extraction..
20. Mieda M, Atsuta I, Morita T, Ayukawa Y, Tsukiyama Y, Sawae Y, Koyano K. , The effective design of zirconia coping on titanium base in dental implant superstructure., Dent Mater J, 2018.06.
21. Zhang H, Moriyama Y, Ayukawa Y, Rakhmatia YD, Tomita Y, Yasunami N, Koyano K., Generation and histomorphometric evaluation of a novel fluvastatin-containing poly(lactic-co-glycolic acid) membrane for guided bone regeneration, Odontology, 2018.06.
22. Tsuruta K, Ayukawa Y, Matsuzaki T, Kihara M, Koyano K., The influence of implant—abutment connection on the screw loosening and microleakage , International Journal of Implant Dentistry, 4, 11, 2018.06.
23. Kanazawa M,Atsuta I,Ayukawa Y,Yamaza T,Kondo R,Matsuura Y,Koyano K, The influence of systemically or locally administered mesenchymal stem cells on tissue repair in a rat oral implantation model, International Journal of Implant Dentistry, 4, 2, 2018.01.
24. Mariko Urata, Shoichiro Kokabu, Takuma Matsubara, Goro Sugiyama, Chihiro Nakatomi, Hiroshi Takeuchi, Shizu Hirata-Tsuchiya, Kazuhiro Aoki, Yukihiko Tamura, Yasuko Moriyama, Yasunori Ayukawa, Miho Matsuda, Min Zhang, Kiyoshi Koyano, Chiaki Kitamura, Eijiro Jimi, A peptide that blocks the interaction of NF-κB p65 subunit with Smad4 enhances BMP2-induced osteogenesis, Journal of Cellular Physiology, 10.1002/jcp.26571, 233, 7356-7366, 2018.01.
25. Tomoko Nishimura, Yoichiro Ogino, Yasunori Ayukawa, Kiyoshi Koyano, Influence of the wettability of different titanium surface topographies on initial cellular behavior, dental materials journal, 10.4012/dmj.2017-334, 37, 4, 650-658, 2018.01, This study examined the influence of the time-dependent wettability of different surface topographies on initial cellular behavior. Titanium disks with smooth topography (SM) and three kinds of rough topography (sandblasted (SA), microtopography (M) and nanotopography (N)) were prepared. Time-dependent changes in surface wettability were observed in all surfaces as shown in previous studies. On SM surfaces, hydrophobic alteration influenced cell spreading and the activity of RhoA (a small GTPase protein of the Rho family), while no alterations were observed on rough surfaces except for the number of adherent cells. Serum adsorption could recover these functional deteriorations by hydrophobic alteration. These findings suggest that surface topography is a more potent regulator in initial cellular behaviors such as cell spreading and RhoA activation than surface wettability..
26. Maiko Mieda, Ikiru Atsuta, Yasuyuki Matsushita, Takehiro Morita, Yasunori Ayukawa, Yoshihiro Tsukiyama, Yoshinori Sawae, Kiyoshi Koyano, The effective design of zirconia coping on titanium base in dental implant superstructure, dental materials journal, 10.4012/dmj.2017-022, 37, 2, 237-243, 2018.01, Zirconia exhibits good tissue compatibility and nontoxicity, making it a widely used esthetic replacement material for implant abutments. To avoid abutment-fracture, the parts composed of zirconia with a bonded metal component connected to the implant can be used. The purpose of this study was to design titanium and zirconia components with high fracture resistance at the zirconia component’s edge line. Three edge line designs of the titanium base and zirconia sleeve were made: chamfer, shoulder, and back-taper. To assess the strength of the abutment design, static loads were applied vertically and 30 degrees from the vertical axis. A test of tensile strength was also performed after chewing simulation. Conventional zirconia components mounted on a chamfer-type titanium base showed significantly lower fracture resistance than shoulder and back-taper types. This study suggests that to improve the durability of zirconia abutments with a titanium base, a back-tapered edge design is recommended..
27. Norio Goto, Ken Okazaki, Yukio Akasaki, Kohei Ishihara, Koji Murakami, Kiyoshi Koyano, Yasunori Ayukawa, Noriyuki Yasunami, Tomohiro Masuzaki, Yasuharu Nakashima, Single intra-articular injection of fluvastatin-PLGA microspheres reduces cartilage degradation in rabbits with experimental osteoarthritis, Journal of Orthopaedic Research, 10.1002/jor.23562, 35, 11, 2465-2475, 2017.11, Statins are cholesterol-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of the mevalonate pathway. The anti-inflammatory effect of statins has been reported in recent years. The present study investigated therapeutic effects of the local administration of statin in osteoarthritis (OA). We assessed clinically used statins and selected fluvastatin for further experimentation, as it showed potent anabolic and anti-catabolic effects on human OA chondrocytes. To achieve controlled intra-articular administration of statin, we developed an intra-articular injectable statin using poly(lactic-co-glycolic acid) (PLGA) as a drug delivery system (DDS). The release profile of the statin was evaluated in vitro. Finally, therapeutic effects of fluvastatin-loaded PLGA microspheres (FLU-PLGA) were tested in a rabbit OA model. Rabbit knees were divided into four subgroups: group 1-A, PLGA-treated group; group 1-B, PLGA contralateral saline control group; group 2-A, FLU-PLGA-treated group; and group 2-B, FLU-PLGA contralateral saline control group. Histological analysis 5 weeks after intra-articular injection revealed that OARSI scores were lower in group 2-A. No significant differences in OARSI scores were observed between groups 1-A, 1-B, and 2-B. This study indicates that a single intra-articular injection of fluvastatin-loaded PLGA microspheres could be a novel therapeutic approach for treating patients with OA..
28. Yunia Dwi Rakhmatia, Yasunori Ayukawa, Yohei Jinno, Akihiro Furuhashi, Kiyoshi Koyano, Micro-computed tomography analysis of early stage bone healing using micro-porous titanium mesh for guided bone regeneration
preliminary experiment in a canine model, Odontology, 10.1007/s10266-017-0298-1, 105, 4, 408-417, 2017.10, The aim of this study was to evaluate the amount of bone formation beneath a defect area after treatment with titanium mesh membranes with different thicknesses and pore sizes alone or in combination with bone graft to induce bone formation during the early stage of healing time. The mandibular premolars were extracted bilaterally from three adult beagle dogs, and 8-mm-diameter bone defects were created on the buccal site of the premolar regions. Hydroxyapatite bone graft substitute was applied in the defect site unilaterally, and other site was left empty. Then, a novel micro-porous mesh (50 μm in pore diameter) or commercially available macro-porous titanium mesh (1700 μm in pore diameter) was placed on the defect and secured with screws. After 4 weeks, the mandibles were harvested, imaged using micro-computed tomography, and prepared for histological and morphometric evaluation. Higher new bone volumes (mm3), percentage of new bone volumes in the total defect volumes (bone ratio: %), and new bone area (mm2) through morphometric evaluation were found on the novel membranes with 50-μm-diameter pores compared to the commercial titanium mesh. Moreover, experiment sites without bone graft were observed with higher new bone volume and bone ratio compared with sites with bone graft. However, bone mineral density of novel mesh was observed to be lower compared with other experimental sites. Under the experimental condition, the result of this study suggests that titanium meshes with 50-μm-diameter pores were effective for guided bone regeneration in the early stage of healing..
29. Maki Matsuzaki, Yasunori Ayukawa, Nobuo Sakai, Tatsuya Matsuzaki, Yasuyuki Matsushita, Kiyoshi Koyano, A comparison of the peri-implant bone stress generated by the preload with screw tightening between ‘bonded’ and ‘contact’ model, Computer Methods in Biomechanics and Biomedical Engineering, 10.1080/10255842.2016.1236370, 20, 4, 393-402, 2017.03, A number of finite element analyses (FEAs) for the dental implant were performed without regard for preload and with all interfaces ‘fixed-bonded’. The purpose of this study was comparing the stress distributions between the conventional FEA model with all contacting interfaces ‘fixed-bonded’ (bonded model) and the model with the interfaces of the components in ‘contact’ with friction simulated as a preloaded implant (contact model). We further verified the accuracy of the result of the FEA using model experiment. In the contact model, the stress was more widely distributed than in the bonded model. From the model study, the preload induced by screw tightening generated strain at the peri-implant bone, even before the application of external force. As a result, the bonded model could not reproduce the mechanical phenomena, whereas the contact model is considered to be appropriate for analysing mechanical problems..
30. Hideo Shimizu, Yohei Jinno, Yasunori Ayukawa, Ikiru Atsuta, Takaaki Arahira, Mitsugu Todo, Kiyoshi Koyano, Tissue reaction to a novel bone substitute material fabricated with biodegradable polymer-calcium phosphate nanoparticle composite, Implant Dentistry, in press, 2016.10, 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 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..
31. Shinichiro Kuroshima, Masaru Kaku, Takashi Matsuura, Ikiru Atsuta, Yasunori Ayukawa, Takashi Sawase, Medication-Related Osteonecrosis of the Jaw; What Should We Do as Prosthodontists?, Journal of Prosthodontic Research, in press, 2016.10.
32. Matsuzaki M, Ayukawa Y, Sakai N, Matsuzaki T, Yasuyuki Matsushita, Koyano K, A comparison of the peri-implant bone stress generated by the preload with screw tightening between 'bonded' and 'contact' model., Computer methods in biomechanics and biomedical engineering, 20, 393-402, 2016.09.
33. Yuri Matsuura, Atsuta Ikiru, Yasunori Ayukawa, Takayoshi Yamaza, Ryosuke Kondo, akira takahashi, Nobuyuki Ueda, Wakana Oshiro, Yoshihiro Tsukiyama, Kiyoshi Koyano, Therapeutic interactions between mesenchymal stem cells for healing medication-related osteonecrosis of the jaw, Stem Cell Research and Therapy, 10.1186/s13287-016-0367-3, 7, 1, 2016.08, Background: Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, including bone marrow, adipose, and mucosa. MSCs have the capacity for self-renewal and differentiation. Reports have been published on the systemic administration of MSCs leading to functional improvements by engraftment and differentiation, thus providing a new strategy to regenerate damaged tissues. Recently, it has become clear that MSCs possess immunomodulatory properties and can therefore be used to treat diseases. However, the therapeutic effect mechanisms of MSCs are yet to be determined. Here, we investigated these mechanisms using a medication-related osteonecrosis of the jaw (MRONJ)-like mouse model. Methods: To generate MRONJ-like characteristics, mice received intravenous zoledronate and dexamethasone two times a week. At 1 week after intravenous injection, maxillary first molars were extracted, and at 1 week after tooth extraction, MSCs were isolated from the bone marrow of the mice femurs and tibias. To compare "diseased MSCs" from MRONJ-like mice (d-MSCs) with "control MSCs" from untreated mice (c-MSCs), the isolated MSCs were analyzed by differentiation and colony-forming unit-fibroblast (CFU-F) assays and systemic transplantation of either d-MSCs or c-MSCs into MRONJ-like mice. Furthermore, we observed the exchange of cell contents among d-MSCs and c-MSCs during coculture with all combinations of each MSC type. Results: d-MSCs were inferior to c-MSCs in differentiation and CFU-F assays. Moreover, the d-MSC-treated group did not show earlier healing in MRONJ-like mice. In cocultures with any combination, MSC pairs formed cell-cell contacts and exchanged cell contents. Interestingly, the exchange among c-MSCs and d-MSCs was more frequently observed than other pairs, and d-MSCs were distinguishable from c-MSCs. Conclusions: The interaction of c-MSCs and d-MSCs, including exchange of cell contents, contributes to the treatment potential of d-MSCs. This cellular behavior might be one therapeutic mechanism used by MSCs for MRONJ..
34. Noriyuki Yasunami, Yasunori Ayukawa, Akihiro Furuhashi, Ikiru Atsuta, Rakhmatia Yunia D, Yasuko Moriyama, Masuzaki Tomohiro, Kiyoshi Koyano, Acceleration of hard and soft tissue healing in the oral cavity by a single transmucosal injection of fluvastatin-impregnated poly (lactic-co-glycolic acid) microspheres. An in vitro and rodent in vivo study., Biomedical Materials, 11, 1, 015001, 2015.12.
35. Hideaki Tanaka, Takeshi Toyoshima, Ikiru Atsuta, Yasunori Ayukawa, Masanori Sasaki, Yasuyuki Matsushita, Ryu Hiraoka, Kiyoshi Koyano, Seiji Nakamura, Additional effects of platelet rich fibrin on bone regeneration in sinus augmentation with deproteinized bovine bone mineral: preliminary results , Implant Dentistry, 24, 6, 669-674, 2015.12.
36. Takeshi Toyoshima, Hideaki Tanaka, Yasunori Ayukawa, Miori Howashi, Masuzaki Tomohiro, Takahiro Kiyosue, Kiyoshi Koyano, Seiji Nakamura, Primary Stability of a Hybrid Implant Compared with Tapered and Cylindrical Implants in an Ex Vivo Model, Clinical Implant Dentistry andRelated Research, 10.1111/cid.12205, 17, 5, 950-956, 2015.10.
37. Wakana Oshiro, Yasunori Ayukawa, Ikiru Atsuta, Akihiro Furuhashi, Junichi Yamazoe, Ryosuke Kondo, Mami Sakaguchi, Yuri Matsuura, Yoshihiro Tsukiyama, Kiyoshi Koyano, Promoting effect of CaCl2 hydrothermal treatment to titanium implant surface for early epithelial sealing., Colloids and Surfaces B: Biointerfaces, 131, 1, 141-147, 2015.10.
38. Yasunori Ayukawa, Yumiko Suzuki, Kanji Tsuru, Kiyoshi Koyano, Kunio Ishikawa, Histological comparison in rats between carbonate apatite fabricated from gypsum and sintered hydroxyapatite on bone remodeling., Biomed Research International, 579541, 2015.07.
39. Yunia Dwi Rakhmatia, Yasunori Ayukawa, Akihiro Furuhashi, Ikiru Atsuta, Kiyoshi Koyano, Fibroblast attachment onto novel titanium mesh membranes for guided bone regeneration, Odontology, 10.1007/s10266-014-0151-8, 103, 2, 218-226, 2015.05.
40. Hideaki Tanaka, Takeshi Toyoshima, Atsuta Ikiru, Yasunori Ayukawa, Masanori Sasaki, Yasuyuki Matsushita, Ryu Hiraoka, Kiyoshi Koyano, Seiji Nakamura, Additional effects of platelet-rich fibrin on bone regeneration in sinus augmentation with deproteinized bovine bone mineral
Preliminary results, Implant Dentistry, 10.1097/ID.0000000000000306, 24, 6, 669-674, 2015.01, Purpose: Platelet-rich fibrin (PRF) has been reported to contribute to bone regeneration; however, little is known about details with deproteinized bovine bone mineral (DBBM). This study aims to evaluate additional effects of PRF on bone regeneration in sinus augmentation with DBBM. Materials and Methods: Sinus augmentations were made with DBBM/PRF mixture as lateral approach for 4 sinuses from 4 patients. Bone biopsies were obtained from posterior maxilla at the implant placements 7 or 10 months after sinus augmentations. Histological observations and histomorphometric analyses from augmented areas were performed. Results: The new bone formation was found around the DBBMs with very good contact while surfaces of DBBMs were partly resorbed. Osteoclasts recognized the DBBMs for remodeling, followed by new bone running. The histomorphometric analyses revealed that mean percentages of newly formed bone were 31.7 ± 1.2%, 21.0 ± 1.0%, 38.0 ± 0.6%, and 47.0 ± 0.6%, respectively (mean 34.5 ± 5.7%). Conclusions: Additional effects of PRF could be found because of higher percentages of newly bone formation by DBBM/PRF mixture than those by DBBM individual in previous reports..
41. Yunia Dwi Rakhmatia, Yasunori Ayukawa, Akihiro Furuhashi, Kiyoshi Koyano, Micro-CT and histomorphometric analyses of novel titanium mesh membranes for guided bone regeneration: A study on rat calvarial defects, International Journal of Oral and Maxillofacial Implants, 2014.12.
42. Miori Howashi, Yoshihiro Tsukiyama, Yasunori Ayukawa, Kei Isoda-Akizuki, Masafumi Kihara, Yu Imai, Motofumi Sogo, Kiyoshi Koyano, Relationship between the CT Value and Cortical Bone Thickness at Implant Recipient Sites and Primary Implant Stability with Comparison of Different Implant Types, Clinical Implant Dentistry andRelated Research, 18, 1, 107-116, 2014.11.
43. Yoichiro Ogino, Yasunori Ayukawa, Yoko TOMITA, Kiyoshi Koyano, Prosthetic aspects in adult osteoporosis, Journal of Prosthetic Dentistry, 2014.10.
44. Ikiru Atsuta, Yasunori Ayukawa, Akihiro Furuhashi, Yoichiro Ogino, Moriyama Yasuko, Yoshihiro Tsukiyama, Kiyoshi Koyano, In vivo and in vitro studies of epithelial cell behavior around titanium implants with machined and rough surface, Clinical Implant Dentistry andRelated Research, 10.1111/cid.12043, 16, 5, 772-781, 2014.10.
45. Akinari Nakagawa, Naoki Shitara, Yasunori AYUKAWA, Kiyoshi Koyano, Kenji Nishimura, Implant treatment followed by living donor lung transplant: A follow-up case report, Journal of Prosthodontic Research, http://dx.doi.org/10.1016/j.jpor.2013.11.001, 58, 2, 127-131, 2014.04.
46. Toshio Takano, Yin-Ji Li, Akiko Kukita, Takayoshi Yamaza, Yasunori Ayukawa, Kanako Moriyama, Norihisa Uehara, Hisayuki Nomiyama, Kiyoshi Koyano, Toshio Kukita, Mesenchymal Stem Cells Markedly Suppress Inflammatory Bone Destruction in Rats with Adjuvant-Induced Arthritis, Laboratory Investigation, 94, 286-296, 2014.03.
47. Ryosuke Kondo, Ikiru Atsuta, Yasunori Ayukawa, Takayoshi Yamaza, Yuri Matsuura, Akihiro Furuhashi, Yoshihiro Tsukiyama, Kiyoshi Koyano, Therapeutic Interaction of Systemically-administered Mesenchymal Stem Cells with Peri-implant Mucosa, PLoS One, 10.1371/journal.pone.0090681, 9, 3, e90681, 2014.03.
48. Koichi Yamane, Yasunori Ayukawa, Toru Takeshita, Akihiro Furuhashi, Yoshihisa Yamashita, Kiyoshi Koyano, Bacterial adhesion affinities of various implant abutment materials, Clinical Oral Implants Research, 24, 1310-1315, 2013.12.
49. Ikiru Atsuta, Yasunori Ayukawa, Takayoshi Yamaza, Akihiro Furuhashi, Kiyoshi Koyano, The role of phosphoinositide 3-kinase in adhesion of oral epithelial cells to titanium, Archives of Oral Biology, 2013.11.
50. Ikiru Atsuta, Yasunori Ayukawa, Akihiro Furuhashi, Takayoshi Yamaza, Hideyuki Okwachi, Kiyoshi Koyano, Promotive effect of insulin-like growth factor-1 for epithelial sealing to titanium implants, Journal of Biomedical MAterials Research A, 101, 2896-2904, 2013.10.
51. Daisuke Kondo, YOICHIRO OGINO, Yasunori AYUKAWA, Shinji Sakai, KOEI KAWAKAMI, kiyoshi koyano, Bone regeneration of rat tibia defects with enzymatically hydrogelation of gelatin derivative and recombinant human platelet-derived growth factor-BB complex, Int J Oral Maxillofac Implants, 2013.08.
52. Akira Takahashi, Akiko Kukita, Li YinJi, Jing-qi Zhang, Hisayuki Nomiyama, Takayoshi Yamaza, Yasunori AYUKAWA, kiyoshi koyano, Toshio Kukita, Tunneling Nanotube Formation is Essential for the Regulation of Osteoclastogenesis, J Cellular Biochem, 114, 6, 1238-1247, 2013.06.
53. Akihiro Furuhashi, Yasunori AYUKAWA, ATSUTA IKIRU, Rakhmatia YD, Noriyuki Yasunami, kiyoshi koyano, Influence of titanium surface topography on peri-implant soft tissue integration, Key Engineering Materials, 529-530, 559-564, 2013.04.
54. ATSUTA IKIRU, Yasunori AYUKAWA, Takayoshi Yamaza, Akihiro Furuhashi, Ryosuke Kondo, kiyoshi koyano, Expression of Integrin alpha-3 and beta-4 subunits on the process of peri-implant epithelium formation, Key Engineering Materials, 529-530, 407-412, 2013.04.
55. Daisuke Esaki, Yasuyuki Matsushita, Yasunori AYUKAWA, NOBUO SAKAI, Yoshinori Sawae, kiyoshi koyano, Relationship between the magnitude of immediate loading and peri-implant bone strength in dogs., Clinical Oral Implants Research, 10.1111/j.1600-0501.2011.02305.x, 23, 11, 1290-1296, 2012.11.
56. Takashi Kono, Yasunori AYUKAWA, Moriyama Yasuko, Kosaku Kurata, Hiroshi Takamatsu, kiyoshi koyano, The Effect of Low-Magnitude, High-Frequency Vibration Stimuli on the Bone Healing of Rat Incisor Extraction Socket., Journal of Biomechanical Engineering, 134, 9, 091001-1-091001-6, 2012.09.
57. Koichi Yamane, Yasunori AYUKAWA, Toru Takeshita, Akihiro Furuhashi, Yoshihisa Yamashita, kiyoshi koyano, Bacterial adhesion affinities of various implant abutment materials, Clinical Oral Implants Research, 10.1111/j.1600-0501.2012.02574.x, in press, 2012.08.
58. Isoda K, Ayukawa Y, Tsukiyama Y, Sogo M, Matsushita Y, Koyano K., Relationship between the bone density estimated by cone-beam computed tomography and the primary stability of dental implants, Clinical Oral Implants Research, 10.1111/j.1600-0501.2011.02203.x, 23, 7, 832-836, 2012.07.
59. Okawachi H, Ayukawa Y, Atsuta I, Furuhashi A, Sakaguchi M, Yamane K, Koyano K., Effect of titanium surface calcium and magnesium on adhesive activity of epithelial-like cells and fibroblasts, Biointerphases, 10.1007/s13758-012-0027-9, 7, 27, 2012.04.
60. Atsuta I, Ayukawa Y,Ogino Y, Moriyama Y, Koyano K., Evaluations of epithelial sealing and peri-implant epithelial down-growth around “step-type” implants, Clinical Oral Implants Research, 10.1111/j.1600-0501.2011.02163.x, 23, 4, 459-466, 2012.04.
61. Akihiro Furuhashi, Yasunori AYUKAWA, ATSUTA IKIRU, Hideyuki Okawachi, kiyoshi koyano, The difference of fibroblast behavior on titanium substrata with different surface characteristics, Odontology, 100, 2, 199-205, 2012.04.
62. Zhang L, Ayukawa Y, LeGeros RZ, Matsuya S, Koyano, K, Ishikawa K., Tissue-response to calcium-bonded titanium surface., Journal of Biomedical Materials Research , 95A, 1, 33-39, 2010.05.
63. Moriyama Y, Ayukawa Y, Ogino Y, Atsuta I, Todo M, Takao Y, Koyano K., Local application of fluvastatin improves peri-implant bone quantity and mechanical property. A rodent study., Acta Biomaterialia, 6, 4, 1610-1618, 2010.04.
64. Masuzaki T, Ayukawa Y, Moriyama Y, Jinno Y, Atsuta I, Ogino Y, Koyano K., The effect of a single remote injection of statin-impregnated poly (lactic-co-glycolic acid) microspheres on osteogenesis around titanium implants in rat tibia., Biomaterials, 31, 12, 3327-3334, 2010.04.
65. Ayukawa Y, Ogino Y, Moriyama Y, Atsuta I, Jinno Y, Kihara M, Tsukiyama Y, Koyano K., Simvastatin enhances bone formation around titanium implants in rat tibiae., Journal of Oral Rehabilitation, 37, 2, 123-130, 2009.11.
66. Moriyama Y, Ayukawa Y, Kabemura K, Matsushita Y, Kihara M, Tsukiyama Y, Todo M, Takao Y, Koyano K., The alteration of peri-implant bone response exposed to static lateral load, Journal of Biomechanical Science and Engineering, 4, 3, 326-335, 2009.07.
67. Jinno Y, Ayukawa Y, Ogino Y, Atsuta I, Tsukiyama Y, Koyano K., Vertical bone augmentation with fluvastatin in an injectable delivery system: a rat study. , Clinical Oral Implants Research, 20, 8, 756-760, 2009.05.
68. Ogino Y, Ayukawa Y, Kukita T, Atsuta I, Koyano K., Platelet-rich plasma suppresses osteoclastogenesis by promoting the secretion of osteoprotegerin in vitro., Journal of Periodontal Research, 44, 2, 217-224, 2009.04.
69. Ayukawa Y, Yasukawa E, Moriyama Y, Ogino Y, Wada H, Atsuta I, Koyano K., Local application of statin promoted bone repair through the suppression of osteoclasts and the enhancement of osteoblasts at bone-healing sites in rats. , Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, 107, 3, 336-342, 2009.03.
70. Moriyama Y, Ayukawa Y, Ogino Y, Atsuta I, Koyano K., Topical application of statin affects the bone healing around implants, Clinical Oral Implants Research, 19, 6, 600-605, 2008.05.
71. Ogino Y, Ayukawa, Y, Kukita T, Koyano K., The contribution of platelet-derived growth factor, transforming growth factor-beta1 and insulin-like growth factor-I in platelet-rich plasma (PRP) to the proliferation of osteoblast-like cells., Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, 101:724-729, 2006.06.
72. Ogino Y, Ayukawa, Y, Tsukiyama Y, Koyano K., The effect of platelet-rich plasma on the cellular response of rat bone marrow cells in vitro., Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology, 10.1016/j.tripleo.2005.03.007, 100, 3, 302-307, 100:302-307, 2005.09.
73. Okamura A, Ayukawa Y, Iyama S, Koyano K, Effect of the difference of bone turnover on peri-titanium implant osteogenesis in ovariectomized rats, Journal of Biomedical Materials Research, 10.1002/jbm.a.30110, 70A, 3, 497-505, 70A: 497-505, 2004.07.
74. Ayukawa Y, Okamura A, Koyano K, Simvastatin promotes osteogenesis around titanium implants. A histological and histometrical study in rats, Clinical Oral Implants Research, 10.1111/j.1600-0501.2004.01015.x, 15, 3, 346-350, 15(3):346-350, 2004.06.
75. H. Ikeda, T. Yamaza, M. Yoshinari, Y. Ohsaki, Y. Ayukawa, M.A. Kido, T. Inoue, M. Shimono, K. Koyano, T. Tanaka, Ultrastructural and immunoelectron microscopic studies of the peri-implant epitherium-implant (Ti-6Al-4V) interface of rat maxilla, J Periodontol, 10.1902/jop.2000.71.6.961, 71, 6, 961-973, Vol.71,pp.961-973, 2000.01.
76. Y. Ayukawa, F. Takeshita, T. Inoue, M. Yoshinari, M. Shimono, T. Suetsugu, T. Tanaka, An immunmoelectron microscopic localization of noncollagenous bone proteins (osteocalcin and osteopontin) at the bone-titanium interface, J Biomed Mater Res, 10.1002/(SICI)1097-4636(199807)41:1<111::AID-JBM14>3.0.CO;2-Q, 41, 1, 111-119, Vol.41,pp.111-119, 1998.01.
77. F. Takeshita, K. Murai, S. Iyama, Y. Ayukawa, T. Suetsugu, Uncontrolled diabetes hinders bone formation around titanium implants in rat tibiae, A study using light, fluorescence microscopies and image processing, J Periodontol, 69, 3, 314-320, Vol.69,pp.314-320, 1998.01.
78. Y. Ayukawa, F. Takeshita, M. Yoshinari, T. Inoue, Y. Ohtsuka, M. Shimono, T. Suetsugu, T. Tanaka, An immunocytochemical study for lysosomal cathepsins B and D related to the intracellular degradation of titanium at the bone-titanium interface, J Periodontol, 69, 1, 62-68, Vol.69,pp.62-68, 1998.01.
79. F. Takeshita, Y. Ayukawa, K. Murai, T. Suetsugu, Long-term evaluation of bone-titanium interface in rat tibiae using light microscopy, transmission electron microscopy and image processing, J Biomed Mater Res, 10.1002/(SICI)1097-4636(199711)37:2<235::AID-JBM13>3.0.CO;2-D, 37, 2, 235-242, Vol.37,pp.235-242, 1997.01.
80. F. Takeshita, K. Murai, Y. Ayukawa, T. Suetsugu, Effects of aging on titanium implants inserted into the tibiae of rats using light microscopy, SEM, and image processing,, J Biomed Mater Res, 34, 1, 1-8, Vol.34,pp.1-8, 1997.01.
81. S. Iyama, F. Takeshita, Y. Ayukawa, M. A. Kido, T. Suetsugu, T. Tanaka, A study of regional distribution of bone formed around hydroxyapatite implants in the tibiae of streptozotocin-induced diabetic rats using multiple fluorescent labeling and confocal laser scanning microscopy, J Periodontol, Vol.68,pp.1169-1175, 1997.01.
82. F. Takeshita, Y. Ayukawa, S. Iyama, T. Suetsugu, M. Oishi, Histological comparison of early wound healing following dense HA granule grafting and barrier placement in surgically-created bone defects neighboring implants, J Periodontol, 68, 10, 924-932, Vol.68,pp.924-932, 1997.01.
83. F. Takeshita, H. Takata, Y. Ayukawa, T. Suetsugu, Histomorphometric analysis of the response of rat tibiae to shape memory alloy (nitinol), Biomaterials, 10.1016/S0142-9612(96)00051-8, 18, 1, 21-25, Vol.18,pp.21-25, 1997.01.
84. Y. Ayukawa, F. Takeshita, T. Inoue, M. Yoshinari, Y. Ohtsuka, K. Murai, M. Shimono, T. Suetsugu, T. Tanaka, An ultrastructural study of the bone-titanium interface using pure titanium plastic and pure titanium rod implants, Acta Histochem Cytochem, 29, 3, 243-254, Vol.29,pp.243-254, 1996.01.
85. F. Takeshita, Y. Ayukawa, S. Iyama, T. Suetsugu, M. A. Kido, A histologic evaluation of retrieved hydroxyapatite-coated blade form implants using scanning electron, light, and confocal laser scanning microscopies, J Periodontol, 67, 10, 1034-1040, Vol.67,pp.1034-1040, 1996.01.
86. F. Takeshita, Y. Matsushita, Y. Ayukawa, T. Suetsugu, Fractures of hydroxyapatite-coated blade implants connected with natural teeth. A histological study using SEM, light microscopy, and an image processing system, J Periodontol, 67, 2, 86-92, Vol.67,pp.86-92, 1996.01.
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