Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Yasunori AYUKAWA Last modified date:2023.10.06

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


Papers
1. Tianjie Chen, Yohei Jinno, Ikiru Atsuta, Akira Tsuchiya, Michele Stocchero, Eriberto Bressan, Yasunori Ayukawa, Current surface modification strategies to improve the binding efficiency of emerging biomaterial polyetheretherketone (PEEK) with bone and soft tissue: A literature review., Journal of prosthodontic research, 10.2186/jpr.JPR_D_22_00138, 67, 3, 337-347, 2023.07, PURPOSE: The aim of this study was to review the literature on current surface modification strategies used to improve the binding efficiency of an emerging biological material, polyetheretherketone (PEEK), with bone and soft tissues. STUDY SELECTION: This review was based on articles retrieved from PubMed, Google Scholar, Web of Science, and ScienceDirect databases. The main keywords used during the search were "polyetheretherketone (PEEK)," "implant," "surface modification," "biomaterials," "bone," "osseointegration," and "soft tissue." RESULTS: The suitability of PEEK surface modification strategies has been critically analyzed and summarized here. Many cell and in vivo experiments in small animals have shown that the use of advanced modification technologies with appropriate surface modification strategies can effectively improve the surface inertness of PEEK, thereby improving its binding efficiency with bone and soft tissues. CONCLUSIONS: Surface modifications of PEEK have revealed new possibilities for implant treatment; however, most results are based on in vitro or short-term in vivo evaluations in small animals. To achieve a broad application of PEEK in the field of oral implantology, more in vivo experiments and long-term clinical evaluations are needed to investigate the effects of various surface modifications on the tissue integration ability of PEEK to develop an ideal implant material..
2. Al-Omari Farah A., 黒嶋 伸一郎, 右藤 友督, 内田 悠介, 張 暁旭, 三田 公麿, 鮎川 保則, 澤瀬 隆, Effects of Administration Route of Parathyroid Hormone on Bone Quantity around implants in Ovariectomized Rat Maxillae(タイトル和訳中), 日本口腔インプラント学会誌, 36, 1, E30-E31, 2023.03.
3. Ikiru Atsuta, Tokihisa Mizokami, Yohei Jinno, Bin Ji, Tingyu Xie, Yasunori Ayukawa, Synergistic Effect of Carbonate Apatite and Autogenous Bone on Osteogenesis, Materials, 10.3390/ma15228100, 15, 22, 2022.11, Bone augmentation using artificial bone is an important option in dental defect prostheses. A bone substitute using carbonate apatite (CO3Ap), an inorganic component of bone, was reported to have promising bone formation and bone replacement ability. However, the osteoinductivity of artificial bone is less than autogenous bone (AB). In this study, CO3Ap with AB is demonstrated as a clinically effective bone substitute. For in vitro experiments, an osteoclast-like cell (RAW-D) was cultured in the presence of AB, CO3Ap, or both (Mix), and the number of osteoclasts was evaluated. Osteoblasts were also cultured under the same conditions, and the number of adherent cells was evaluated. For in vivo experiments, a few holes were created in the rat tibia and AB, CO3Ap, or Mix were added. At 0, 14, and 21 days, the tissue morphology of the wound area was observed, and the thickness of the cortical bone was measured. In vitro, Mix did not increase the number of osteoclasts or osteoblasts. However, in vivo, the rate of bone replacement remarkably increased with Mix on dome-shape. A bone-grafting material combining osteoinductive AB with abundant artificial bone is expected to be clinically easy to use and able to form bone..
4. Chi-Hsiang Cheng, Ikiru Atsuta, Kiyoshi Koyano, Yasunori Ayukawa, Oral Health-Related Quality of Life Changes after Clinical Remounting of Existing Dentures., Healthcare (Basel, Switzerland), 10.3390/healthcare10101960, 10, 10, 2022.10, The clinical remount is an accurate and efficient way to reset the occlusion of delivered removable dentures if major occlusal correction is required. Although previous studies have reported that clinical remounting of existing dentures enhances patients' oral function, little subjective feedback is available. This retrospective study reports short-term changes in oral-health-related quality of life (OHRQoL) and masticatory function after clinical remounting of existing dentures. Three time points were defined: before adjustment (T0), immediately after adjustment (T1), and 1 week after adjustment (T2). The medical records of seven patients were analyzed. The mean age of participants was 77.71 years, and the mean service period of their prostheses was 9.43 months. The mean scores of the OHIP-EDENT-J questionnaire at the respective time points were 35, 21.14, and 22.14. The mean readings of masticatory function at the respective time points were 76.71, 89.29, and 111.86. Significant differences in the OHIP-EDENT-J were found between T0 and T1, and T0 and T2; and in masticatory function between T1 and T2, and T0 and T2. The results indicated that after rebalancing of the occlusion of the existing dentures, the patient-reported OHRQoL was improved immediately and maintained at least for a short time, and masticatory function was enhanced over a 1-week period..
5. Mikio Imai, Yoichiro Ogino, Hideaki Tanaka, Kiyoshi Koyano, Yasunori Ayukawa, Takeshi Toyoshima, Primary stability of different implant macrodesigns in a sinus floor elevation simulated model: an ex vivo study., BMC oral health, 10.1186/s12903-022-02345-5, 22, 1, 332-332, 2022.08, BACKGROUND: A novel type of implant (Straumann® BLX implant) has been developed for certain stability from the mechanical and biological aspects and is expected for the implant placement in atrophic maxilla with sinus floor elevation (SFE). PURPOSE: The aim of this study was to evaluate the primary stability in the implants with different macrodesigns in an SFE simulated model. Primary stabilities defined as maximum insertion torque (MIT) and implant stability quotient (ISQ) were compared between this novel type of implant and other types. MATERIALS AND METHODS: Five types of Straumann® 10 mm length implants (Standard Plus; SP, Tapered Effect; TE, Bone Level; BL, Bone Level Tapered; BLT and BLX) and two types of Straumann® 6 mm length implants (SP short, BLX short) were used in this study. Each implant was inserted through 5 mm-thick porcine iliac crest blocks (an SFE simulated model). Primary stability was evaluated by using MIT and ISQ. RESULTS: The mean value of MIT for BLX group showed significantly higher values than SP, BL (p 
6. Ken Matsunaka, Mikio Imai, Koma Sanda, Noriyuki Yasunami, Akihiro Furuhashi, Ikiru Atsuta, Hiroko Wada, Yasunori Ayukawa, Therapeutic Effect of Benidipine on Medication-Related Osteonecrosis of the Jaw., Pharmaceuticals (Basel, Switzerland), 10.3390/ph15081020, 15, 8, 2022.08, Medication-related osteonecrosis of the jaw (MRONJ) is an intractable disease that is typically observed in patients with osteoporosis or tumors that have been treated with either bisphosphonate (BP) or antiangiogenic medicine. The mechanism of MRONJ pathogenesis remains unclear, and no effective definitive treatment modalities have been reported to date. Previous reports have indicated that a single injection of benidipine, an antihypertensive calcium channel blocker, in the vicinity of a tooth extraction socket promotes wound healing in healthy rats. The present study was conducted to elucidate the possibility of using benidipine to promote the healing of MRONJ-like lesions. In this study, benidipine was administered near the site of MRONJ symptom onset in a model rat, which was then sacrificed two weeks after benidipine injection, and analyzed using histological sections and CT images. The analysis showed that in the benidipine groups, necrotic bone was reduced, and soft tissue continuity was recovered. Furthermore, the distance between epithelial edges, length of necrotic bone exposed in the oral cavity, necrotic bone area, and necrotic bone ratio were significantly smaller in the benidipine group. These results suggest that a single injection of benidipine in the vicinity of MRONJ-like lesions can promote osteonecrotic extraction socket healing..
7. Koma Sanda, Yasunori Ayukawa, Noriyuki Yasunami, Naomi Adachi, Akihiro Furuhashi, Mikio Imai, Ken Matsunaka, Kiyoshi Koyano, Therapeutic effect of fluvastatin on medication-related osteonecrosis of the jaw., Journal of periodontology, 10.1002/JPER.21-0294, 93, 6, 837-846, 2022.06, BACKGROUND: Refractory jaw osteonecrosis that occurs in osteoporotic or cancer patients treated with bisphosphonates is called medication-related osteonecrosis of the jaw but its underlying mechanism is unclear. Statins, therapeutic agents for dyslipidemia, lower blood low-density lipoprotein cholesterol. Fluvastatin promotes the healing of tooth extraction sockets and reduces the risk of developing medication-related osteonecrosis of the jaw-like lesions. We used a rat model to investigate whether injecting fluvastatin at extraction sites promoted the healing of medication-related osteonecrosis of the jaw-like lesions. METHODS: Upper first molars of rats administered zoledronate and dexamethasone for 2 weeks were extracted. Two weeks after tooth extraction, rats with medication-related osteonecrosis of the jaw-like lesions (bone exposure) were included in this study. A single injection of fluvastatin was administered in the vicinity of the medication-related osteonecrosis of the jaw-like onset site in rats. RESULTS: The distance between the edges of the epithelia, the length of the necrotic bone exposed toward the oral cavity, the area of the necrotic bone, and the necrotic bone ratio were significantly smaller in the fluvastatin-administered group compared with the saline group. A single application of fluvastatin near the site of medication-related osteonecrosis of the jaw onset showed a tendency to close the epithelium, reduce necrotic bone, and form new bone, even when symptoms had already developed. CONCLUSION: This study suggests that a single topical administration of fluvastatin may be a novel treatment for medication-related osteonecrosis of the jaw..
8. Chi-Hsiang Cheng, Ikiru Atsuta, Kiyoshi Koyano, Yasunori Ayukawa, Hypothetical Model of How a Clinical Remount Procedure Benefits Patients with Existing Dentures: A Narrative Literature Review., Healthcare (Basel, Switzerland), 10.3390/healthcare10061067, 10, 6, 2022.06, The clinical remount procedure, which involves remounting the dentures on an articulator with interocclusal records, can effectively reduce occlusal discrepancies. This procedure can be applied not only to new dentures but also to those already in service; however, research in this field is still scarce. This narrative review aims to establish a hypothetical mechanism and possible indications and contraindications for this technique as a basis for further research. Current studies have revealed a high prevalence of malocclusion in delivered dentures. Performing a clinical remount on these existing dentures would enhance the oral function of the denture wearer and would enable effective and accurate correction of the accumulated errors in the jaw relationship in a stable working environment. This technique should be performed if a patient has poor masticatory function or occlusion-related complaints. However, performing a clinical remount on dentures with an excessive anterior-posterior discrepancy between the centric relation and the maximal intercuspal position or on dentures with extremely low occlusal vertical dimension, is considered less effective. The clinical remount procedure remains an essential skill both for fabricating quality dentures and maintaining those already in service..
9. Kayo Mori, Akiko Mizokami, Tomomi Sano, Satoru Mukai, Fumitaka Hiura, Yasunori Ayukawa, Kiyoshi Koyano, Takashi Kanematsu, Eijiro Jimi, RANKL elevation activates the NIK/NF-κB pathway, inducing obesity in ovariectomized mice., The Journal of endocrinology, 10.1530/JOE-21-0424, 254, 1, 27-36, 2022.05, Menopausal women are susceptible to visceral obesity, which increases the risk of metabolic disorders. However, the mechanisms of menopause-induced visceral fat accumulation are not fully understood. Circulating levels of receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) are elevated in an animal model of menopause. RANKL, a multifunctional cytokine, activates the NF-κB pathway, which serves as a pivotal mediator of inflammatory responses. Here, we investigated whether RANKL-induced non-canonical NF-κB pathway activation induces inflammation and lipid accumulation in adipose tissues. RANKL induced Tnfa expression via the non-canonical NF-κB pathway in bone marrow cells. We therefore analyzed aly/aly mice, in which the non-canonical NF-κB pathway is not activated, owing to an inactive form of NF-κB-inducing kinase. A postmenopausal obesity model was generated by ovariectomy and subsequent high-fat and high-sucrose diet feeding. In aly/aly mice with postmenopausal obesity, serum RANKL levels were elevated, and hepatic lipid accumulation and adipocyte hypertrophy were suppressed, resulting in reduced macrophage infiltration and inflammatory cytokine mRNA expression in visceral adipose tissue. Furthermore, aly/aly mice showed protection from glucose intolerance and insulin resistance, which were observed in ovariectomized WT obese mice. These findings indicate that non-canonical NF-κB pathway activation via serum RANKL elevation contributes to postmenopausal obesity..
10. Chi-Hsiang Cheng, Ikiru Atsuta, Yuki Egashira, Kiyoshi Koyano, Yasunori Ayukawa, Oral Function Rehabilitation with the Simplified Lauritzen Clinical Remount Technique in a Patient with Bimaxillary Alveolar Exostoses: A Case Report., Healthcare (Basel, Switzerland), 10.3390/healthcare10040682, 10, 4, 2022.04, This case report describes a 70 year-old man with IVA lung cancer who required oral function rehabilitation by fabricating dentures with a simplified clinical remount technique. A pair of dentures were fabricated for a 70-year-old man with stage IVA lung cancer. Due to severe bimaxillary exostoses, the dentures could not properly extend and achieve a peripheral seal. The treatment philosophy was to stabilize the dentures and achieve proper function with optimized occlusion. The simplified Lauritzen clinical remount technique was performed at the time of denture delivery and 3 months later. After the second clinical remount procedure, the patient was able to eat meals with the dentures and maintained in a stable condition. Compared with the original technique, the simplified Lauritzen clinical remount omits the facebow transfer and keeps the condylar guidance setting and the Bennett angle unchanged during the adjustment. The prostheses are mounted to a type 3, non-arcon type articulator with anterior stop screws attached to the bilateral condylar parts. With the aid of anterior stop screws, the eccentric movement of dentures can be differentiated on a millimeter scale and balanced easily. It is effective to use occlusal-optimized dentures and the clinical remount technique, especially in difficult cases..
11. Yuki Egashira, Ikiru Atsuta, Ikue Narimatsu, Xiaoxu Zhang, Ryosuke Takahashi, Kiyoshi Koyano, Yasunori Ayukawa, Effect of carbonate apatite as a bone substitute on oral mucosal healing in a rat extraction socket: in vitro and in vivo analyses using carbonate apatite., International journal of implant dentistry, 10.1186/s40729-022-00408-4, 8, 1, 11-11, 2022.03, BACKGROUND: Low bone quantity and quality are serious problems that affect the prognosis of implants in the cosmetic field. Therefore, artificial bone substitutes are frequently used. However, whether there is a difference in the effect of either bone substitute on soft tissue healing is unclear given their greatly different absorbability. In this study, we used hydroxyapatite (HAp) and carbonate apatite (CO3Ap) as bone substitutes to analyze the epithelial and connective tissue healing after tooth extraction. METHODS: In vitro, oral mucosa-derived epithelial cells (OECs) collected from 4-day-old Wistar rats were seeded on HAp or CO3Ap and evaluated for adhesion, proliferation, migration, apoptosis, and morphology. Fibroblasts (FBs) were also analyzed for their ability to express collagen. In vivo, the extraction of maxillary right first (M1) and second molars (M2) of 6-week-old male Wistar rats was performed, followed by insertion of HAp or CO3Ap granules into the M1 and M2 sites. The oral mucosal healing process was then evaluated histochemically after 7 and 14 days. RESULTS: In vitro, high collagen expression by FBs in the CO3Ap group was observed and the surface analysis showed spreading of the FBs on the CO3Ap surface. However, the activity of OECs was suppressed on CO3Ap. Two weeks after CO3Ap implantation, soft tissue healing was observed, and recovery of the connective tissue was observed on the remaining CO3Ap. CONCLUSIONS: Our results suggest that the formation of soft tissues, including connective tissue, was promoted by CO3Ap in the extraction socket within a short period..
12. Xi Chen, Yasuko Moriyama, Yoko Takemura, Maho Rokuta, Yasunori Ayukawa, Influence of osteoporosis and mechanical loading on bone around osseointegrated dental implants: A rodent study., Journal of the mechanical behavior of biomedical materials, 10.1016/j.jmbbm.2021.104771, 123, 104771-104771, 2021.11, This study aimed to evaluate the influence of estrogen deficiency and mechanical loading on bone around osseointegrated dental implants in a rat jaw model. The maxillary right first molars of 36 rats were extracted. One week later, the rats were divided into an unloaded group and a loaded group; short head implants and long head implants were inserted respectively. Nine weeks after implantation, the rats were further subjected to ovariectomy (OVX) or sham surgery. All animals were euthanized 21 weeks after OVX. Micro-computed tomography, histological and histomorphometrical evaluation were undertaken. Systemic bone mineral density and bone volume fraction decreased in OVX groups compared with the sham controls. Histomorphometrical observation indicated that unloaded OVX group showed significantly damaged osseointegration and bone loss versus the loaded OVX group. Both the bone density (BD) inside the peri-implant grooves and the percentage of bone-to-implant contact (BIC) were lower in the OVX groups than in the sham-surgery groups, although mechanical loading increased the BIC and BD in the loaded OVX group compared with the unloaded OVX group. An increased number of positive cells for tartrate-resistant acid phosphatase was observed in the OVX groups versus the sham controls. The percentage of sclerostin-positive osteocytes was lower under loaded compared with unloaded conditions in both the OVX groups and the sham controls. In conclusion, estrogen deficiency could be a risk factor for the long-term stability of osseointegrated implants, while mechanical loading could attenuate the negative influence of estrogen deficiency on bone formation and osseointegration..
13. Koma Sanda, Noriyuki Yasunami, Maki Okada, Akihiro Furuhashi, Yasunori Ayukawa, Accuracy of the Intra- and Extra-Oral Scanning Technique for Transferring the Intaglio Surface of a Pontic of Provisional Restorations to Definitive Restorations., Materials (Basel, Switzerland), 10.3390/ma14216489, 14, 21, 2021.10, When taking the final impression for a three-unit fixed partial denture (FPD), the intaglio surface of the pontic of provisional restoration cannot be transferred accurately to that of definitive restoration. The intra- and extra-oral scanning (IEOS) technique, a method for accurately reproducing the submucosal morphology of the superstructure of an implant, has been reported using an intraoral scanner. In the present study, we evaluated the difference between the conventional impression method using impression material and the IEOS technique in reproducing the morphology of the surface of the pontic of a definitive FPD. There was a significant difference in the trueness of the intaglio surface morphology of the pontic between the conventional method and the IEOS technique; however, no significant difference in precision was observed. As a result, the intaglio surface of the pontic of the three-unit FPD could be transferred to definitive restorations more accurately with the IEOS technique than with the conventional method. These results suggest that the IEOS technique can duplicate the intaglio surface of the pontic more reproducibly to the definitive restorations compared with the conventional method..
14. Kei Murakami, Yasunori Ayukawa, Yoichiro Ogino, Akinari Nakagawa, Tadashi Horikawa, Eishi Yamaguchi, Kimiyasu Takaki, Kiyoshi Koyano, Clinical effectiveness of implant support for distal extension removable partial dentures: functional evaluation using occlusal force measurement and masticatory efficiency., International journal of implant dentistry, 10.1186/s40729-021-00381-4, 7, 1, 101-101, 2021.10, BACKGROUND: Implant-supported removable partial dentures (ISRPD) are supported at the free-end region with implant retainers. As implant retainers prevent denture settlement and facilitate denture retention, this is intended to improve masticatory performance in comparison with that of conventional removable dentures. In the present study, we evaluated the effect of implant retainers at the free-end region of removable dentures on occlusal force and masticatory efficiency using a pressure-sensitive sheet, and measured glucose concentration in saliva after mastication with gummy candy. METHODS: In the present study, the occlusal force and masticatory efficiency of 13 subjects were measured in the following three conditions: without dentures (Condition 1), wearing dentures but not supported by implants (Condition 2), and wearing dentures supported by implants (ISRPD) (Condition 3). All data were statistically compared. RESULTS: Regarding the occlusal force, Condition 3 showed significantly higher scores than the other conditions; however, there were no significant differences between Conditions 1 and 2. Regarding the masticatory efficiency, Condition 3 showed significantly higher scores than Condition 2. CONCLUSIONS: With ISRPD, the occlusal force and masticatory efficiency were increased in comparison with those with conventional removable dentures..
15. Yoichiro Ogino, Hiroki Suzuki, Yasunori Ayukawa, Yoko Ueno, Akio Jinnouchi, Kiyoshi Koyano, Masticatory performance and other oral functions in community-dwelling elderly patients without posterior occlusal support by natural teeth., Journal of oral science, 10.2334/josnusd.21-0265, 63, 4, 330-333, 2021.10, PURPOSE: To evaluate masticatory performance (MP), maximum occlusal force (MOF), maximum tongue pressure (MTP) and oral diadochokinesis (ODK) among community-dwelling elderly patients without posterior occlusal support. METHODS: This study enrolled community-dwelling elderly patients (≥65 years old) who belonged to Eichner A, B4, C1, C2, and C3. Each oral function was statistically compared among groups. Correlations between MP and other variables were examined in Eichner B4 and C patients. RESULTS: MP and MOF values in Eichner B4 and C patients were significantly lower than in Eichner A patients. There were significant differences in MTP values between Eichner "A and C2, C3", and "B4 and C2, C3". ODK in Eichner C patients showed significantly lower values compared to Eichner A patients in general. Although there were statistically significant correlations of MP with age, the number of remaining teeth and all oral functions were identified, and multiple regression analysis indicated that MOF and MTP were independently related to MP. CONCLUSION: Oral functions in Eichner B4 and C patients were lower compared to Eichner A patients. MP was significantly correlated with MOF and MTP in elderly patients without posterior occlusal support, suggesting the importance of rehabilitation of MOF and MTP in MP..
16. Yoichiro Ogino, Yasunori Ayukawa, Noriko Tachikawa, Masahiro Shimogishi, Youji Miyamoto, Keiko Kudoh, Naoyuki Fukuda, Kunio Ishikawa, Kiyoshi Koyano, Staged Sinus Floor Elevation Using Novel Low-Crystalline Carbonate Apatite Granules: Prospective Results after 3-Year Functional Loading., Materials (Basel, Switzerland), 10.3390/ma14195760, 14, 19, 2021.10, The aim of this study was to evaluate clinical outcomes of staged sinus floor elevation (SFE) using novel low-crystalline carbonate apatite (CO3Ap) granules. Patients who needed SFE for implant placement were recruited into this clinical trial. A staged procedure (lateral window technique using CO3Ap granules, followed by implant placement after 7 ± 2 months) was employed in 13 patients. Bone-height increase and insertion torque values (ITVs) were assessed along with histological evaluation. The survival and success rates of 3-year functioning implants were also evaluated. Mean of bone-height increase after SFE using CO3Ap granules was 7.2 ± 2.5 mm and this increase allowed implant placement in all cases (17 implants). Mean of ITV was 25.1 ± 13.2 Ncm and primary stability was achieved successfully in all cases. Histological analyses revealed mature new bone formation (36.8 ± 17.3%) and residual CO3Ap granules (16.2 ± 10.1%) in the compartment after SFE. The survival and success rates after 3-year functional loading were 100% and no complications were found. These results clearly indicate the clinical usefulness of CO3Ap granules for SFE..
17. Yoichiro Ogino, Hiroki Suzuki, Yasunori Ayukawa, Akio Jinnouchi, Kiyoshi Koyano, Analyses of Swallowing Function and Its Related Factors in Community-Dwelling Elderly Patients: A Case-Control Study., Journal of clinical medicine, 10.3390/jcm10153437, 10, 15, 2021.08, This retrospective case-control study evaluated the prevalence of declined swallowing function and the association with oral functions and gender in community-dwelling elderly patients. Their profiles, the results of swallowing function (Eating Assessment Tool: EAT-10) and other oral functions (oral dryness, maximum occlusal force (MOF), tongue-lip motor function (oral diadochokinesis: ODK), maximum tongue pressure (MTP) and masticatory performance (MP)) were extracted for analyses. The patients were categorized into three groups according to EAT-10 score (Group 1: 0, Group 2: 1 and 2, Group 3: ≥3). In total, 242 patients were enrolled and 46 of them (19.0%) were categorized into declined swallowing function (Group 3). In two-group comparisons (Group 1, 2 versus Group 3), significant differences were identified in age and the number of remaining teeth, but they were not identified in three-group comparisons. The patients with declined swallowing function (Group 3) had significantly lower function in ODK and MTP. Multiple logistic regression analyses identified that declined swallowing function was independently associated with declined functions in ODK /ka/ (OR: 5.31, 95% CI: 1.03-27.23, p = 0.04) and in MTP (OR: 2.74, 95% CI: 1.12-6.66, p = 0.03). This study could confirm the critical role of tongue functions in swallowing in community-dwelling elderly patients..
18. Xiaoxu Zhang, Ikiru Atsuta, Ikue Narimatsu, Nobuyuki Ueda, Ryosuke Takahashi, Yuki Egashira, Jing-Qi Zhang, Jiong-Yan Gu, Kiyoshi Koyano, Yasunori Ayukawa, Replacement Process of Carbonate Apatite by Alveolar Bone in a Rat Extraction Socket, Materials, 10.3390/ma14164457, 14, 16, 4457-4457, 2021.08, The objective of this study was to investigate a bone graft substitute containing carbonate apatite (CO3Ap) to analyze bone replacement and the state of bone formation in vitro and in vivo compared with autogenous bone (AB) or control. An osteoclast precursor cell line was cultured with AB or CO3Ap, and morphological analysis using scanning electron microscopy and a tartrate-resistant acid phosphatase activity assay were performed. The right maxillary first and second molars of Wistar rats were extracted and compensated by AB or CO3Ap granules. Following implantation, the bone formation state was evaluated after 3, 5, 7, 14, and 28 days of surgery by micro-computed tomography and immunohistostaining. The osteoclast-like cell morphology was typical with many cell protrusions in the AB and CO3Ap groups. Additionally, the number of osteoclast-like cells formed in the culture increased in each group; however, there was no significant difference between the AB and CO3Ap groups. Five days after tooth extraction, osteoclasts were observed near CO3Ap. The bone thickness in the CO3Ap group was significantly increased than that in the control group and the bone formation in the CO3Ap group increased by the same level as that in the AB group. CO3Ap is gradually absorbed by osteoclasts in the extraction socket and is easily replaced by alveolar bone. The process of bone replacement by osteoclasts is similar to that of autologous bone. By observing the process of bone replacement in more detail, it may be possible to gain a better understanding of the bone formation and control the amount of bone after surgery..
19. Ikiru Atsuta, Ikue Narimatsu, Taichiro Morimoto, Chi-Hsiang Cheng, Kiyoshi Koyano, Yasunori Ayukawa, Assessment of the Soft-Tissue Seal at the Interface between the Base of the Fixed Denture Pontic and the Oral Mucosa., Materials (Basel, Switzerland), 10.3390/ma14143997, 14, 14, 2021.07, Fixed dentures (bridges) are often selected as a treatment option for a defective prosthesis. In this study, we assess the contact condition between the base of the pontic and oral mucosa, and examine the effect of prosthetic preparation and material biocompatibility. The molars were removed and replaced with experimental implants with a free-end type bridge superstructure after one week. In Experiment 1, we assessed different types of prosthetic pre-treatment: (1) the untreated control group (Con: mucosa recovering from the tooth extraction); (2) the laser irradiation group (Las: mucosa recovering after the damage caused by a CO2 laser); and (3) the tooth extraction group (Ext: mucosa recovering immediately after the teeth extraction). In Experiment 2, five materials (titanium, zirconia, porcelain, gold-platinum alloy, and self-curing resin) were placed at the base of the bridge pontic. Four weeks after the placement of the bridge, the mucosa adjacent to the pontic base was histologically analyzed. In Experiment 1, the Con and Las groups exhibited no formation of an epithelial sealing structure on the pontic base. In the Ext group, adherent epithelium was observed. In Experiment 2, the sealing properties at the pontic interface were superior for titanium and the zirconia compared with those made of porcelain or gold-platinum alloy. In the resin group, a clear delay in epithelial healing was observed..
20. Kohei Kinoshita, Yoichiro Ogino, Kyosuke Oki, Yo Yamasaki, Yoshihiro Tsukiyama, Yasunori Ayukawa, Kiyoshi Koyano, A Prospective Comparative Study of Mastication Predominance and Masticatory Performance in Kennedy Class I Patients., Healthcare (Basel, Switzerland), 10.3390/healthcare9060660, 9, 6, 2021.06, Mastication predominance in Kennedy class I (KC I) patients has not been well defined. This study aimed to investigate mastication predominance and masticatory performance in KC I patients, including the significance of remaining posterior teeth and removable partial-denture (RPD) treatment. KC I patients who had differences in the number of posterior teeth between left and right sides (D+) and KC I patients who had no differences (D-) were enrolled. Healthy dentate (HD) subjects were also registered as a positive control. Mastication predominance, defined by mastication predominance index (MPI; range 0-100%) calculated from electromyogram activities during voluntary chewing, and masticatory performance were evaluated at pre- and post-RPD treatment. Pre-MPI in KC I D+ was significantly higher than in HD. RPD treatment could significantly improve MPI and masticatory performance in both KC I groups. However, there were significant differences in masticatory performance between each KC I group and HD, regardless of RPD treatment. It was considered that the mastication predominance in KC I patients was affected by the difference in the number of remaining posterior teeth. RPD treatment could improve mastication predominance and masticatory performance in KC I patients, although the latter was not similar to HD group..
21. Kyosuke Oki, Yoichiro Ogino, Yuriko Takamoto, Mikio Imai, Yoko Takemura, Yasunori Ayukawa, Kiyoshi Koyano, The Significance of Posterior Occlusal Support of Teeth and Removable Prostheses in Oral Functions and Standing Motion., International journal of environmental research and public health, 10.3390/ijerph18136776, 18, 13, 2021.06, The purpose of this study was to evaluate the effect of posterior occlusal support of natural teeth and artificial teeth on oral functions and standing motion. Patients who had been treated with removable prostheses were enrolled as the subjects. Their systemic conditions (body mass index (BMI) and skeletal muscle mass index (SMI)) were recorded. The subjects were classified into two groups according to a modified Eichner index: B1-3 (with posterior occlusal support) and B4C (without posterior occlusal support). Maximum occlusal force (MOF), masticatory performance (MP), and standing motion (sway and strength) were evaluated for cases with and without removable prostheses. There were no significant differences in BMI and SMI between the B1-3 group and the B4C group. The subjects with removable prostheses demonstrated significantly higher values in MOF, MP, and sway and strength than the subjects without removable prostheses. The comparison of oral functions between the B1-3 group and the B4C group revealed that the positive effect of posterior occlusal support of natural teeth and removable prostheses and the significant positive effects of posterior occlusal support on standing motion were partly observed in these comparisons. Posterior occlusal support of natural teeth and even of removable prostheses may contribute to the enhancement of oral functions and standing motion..
22. Akihiro Furuhashi, Yasunori Ayukawa, Ikiru Atsuta, Yunia Dwi Rakhmatia, Kiyoshi Koyano, Soft Tissue Interface with Various Kinds of Implant Abutment Materials., Journal of clinical medicine, 10.3390/jcm10112386, 10, 11, 2021.05, Various materials, such as titanium, zirconia and platinum-gold (Pt-Au) alloy, have been utilized for dental implant trans-mucosal parts. However, biological understanding of soft tissue reaction toward these materials is limited. The aim of this study was to compare the response of cell lines and soft tissue to titanium, zirconia and Pt-Au substrata. The surface hydroxyl groups and protein adsorption capacities of the substrata were measured. Next, gingival epithelial-like cells (Sa3) and fibroblastic cells (NIH3T3) were cultured on the materials, and initial cell attachment was measured. Immuno-fluorescent staining of cell adhesion molecules and cytoskeletal proteins was also performed. In the rat model, experimental implants constructed from various materials were inserted into the maxillary tooth extraction socket and the soft tissue was examined histologically and immunohistochemically. No significant differences among the materials were observed regarding the amount of surface hydroxyl groups and protein adsorption capacity. Significantly fewer cells of Sa3 and NIH3T3 adhered to the Pt-Au alloy compared to the other materials. The expression of cell adhesion molecules and a well-developed cytoskeleton was observed, both Sa3 and NIH3T3 on each material. In an animal model, soft tissue with supracrestal tissue attachment was observed around each material. Laminin-5 immuno-reactivity was seen in epithelia on both titanium and zirconia, but only in the bottom of epithelia on Pt-Au alloy. In conclusion, both titanium and zirconia, but not Pt-Au alloy, displayed excellent cell adhesion properties..
23. Keishu Tachibana, Ikiru Atsuta, Yoshihiro Tsukiyama, Rika Kuwatsuru, Takehiro Morita, Hiroya Yoshimatsu, Yasuyuki Matsushita, Ikue Narimatsu, Yasunori Ayukawa, Yoshinori Sawae, Kiyoshi Koyano, The need for polishing and occlusal adjustment of zirconia prostheses for wear on antagonist teeth., Dental materials journal, 10.4012/dmj.2020-190, 40, 3, 650-656, 2021.05, The attrition of enamel when opposed by ceramics is of great concern. The purpose of this study was to evaluate enamel wear against high translucent zirconia (Zr), lithium disilicate (LD), gold (Au), and enamel (E) with different surface and contact conditions. The materials were divided into two groups: polished and ground (n=8 each). Two-body wear tests were performed against human enamel with vertical and horizontal, horizontal, and vertical repetitive movements as experiments 1 to 3 respectively. The surface roughness of all materials except Zr changed throughout the experiments. In experiment 1, Zr and Au showed less antagonist wear when polished than when ground. In experiment 2, polished groups showed less antagonist wear than ground groups in all materials. In experiment 3, Zr and LD exerted greater antagonist wear than E, regardless of Ra. These findings confirm the importance of polishing and occlusal adjustment of zirconia..
24. Masafumi Kihara, Yoichiro Ogino, Yasuyuki Matsushita, Takehiro Morita, Yoshinori Sawae, Yasunori Ayukawa, Kiyoshi Koyano, In Vitro Assessment of the Effect of Implant Position on Biomechanical Behaviors of Implant-Supported Removable Partial Dentures in Kennedy Class II Condition., Materials (Basel, Switzerland), 10.3390/ma14092145, 14, 9, 2021.04, The purpose of this study was to investigate the effects of implant position and loading position on biomechanical behaviors using implant-supported removable partial denture (ISRPD) models in a simulated Kennedy class Ⅱ partially edentulous mandible. Three types of Kennedy class Ⅱ mandibular acrylic resin models (a conventional RPD without support by an implant-CRPD; models with an implant placed at first molar (#46)-MP-ISRPD- and second molar (#47)-DP-ISRPD) were used to measure vertical displacement of the RPD, mesio-distal displacement of the abutment tooth, and bending moment of the abutment tooth and implant under one-point loading. The variables at three respective loading points (#45, #46 and #47) were compared statistically. Vertical displacement was suppressed in ISRPDs compared to the CRPD, and significant effects were identified under loading at the implant position. The largest meiso-distal displacement was observed in MP-ISRPD under #47 loading. Bending moments of the abutment tooth and implant were significantly higher in MP-ISRPD than in DP-ISPRD. In MP-ISRPD, a higher bending moment of the abutment tooth under #45 and #47 loading was detected, although the bending moment in DP-ISRPD was almost zero. The results of this study suggested that MP-ISRPD shows the specific biomechanical behaviors, although DP-ISRPD might provide biomechanical benefits under all one-point loading conditions..
25. Hiroki Suzuki, Yasunori Ayukawa, Yoko Ueno, Ikiru Atsuta, Akio Jinnouchi, Kiyoshi Koyano, Relationship between Maximum Tongue Pressure Value and Age, Occlusal Status, or Body Mass Index among the Community-Dwelling Elderly., Medicina (Kaunas, Lithuania), 10.3390/medicina56110623, 56, 11, 2020.11, Background and objectives: In an aging society, the maintenance of the oral function of the elderly is of importance for the delay or prevention of frailty and long-term care. In the present study, we focused on the maximum tongue pressure (MTP) value and analyzed the relationship between MTP and age, occlusal status, or body mass index (BMI). Materials and Methods: This one-center observatory study was conducted using a cohort consisting of 205 community-dwelling outpatients over 65 years old. The MTP values of all subjects were measured using a commercially available tongue pressure measurement device and statistically analyzed. In addition, the correlation between MTP value and BMI was analyzed. Results: The MTP value decreased with age, especially in subjects classified as Eichner B and C. The difference in occlusal status did not show any statistically significant influence on MTP value. The correlation between BMI and MTP value was indicated in the tested groups other than an age of 65-74 and Eichner A groups. Conclusions: Although MTP value decreased with age, the difference in occlusal status did not have an impact on MTP value. The correlation between BMI and MTP value was not shown in the youngest group or a group with sufficient occlusal units. The results presented in the present study may imply that, even if MTP is low, younger age and/or better occlusal status compensate for the inferior MTP value in the cohort studied..
26. Yasunori Ayukawa, Ikiru Atsuta, Yasuko Moriyama, Yohei Jinno, Kiyoshi Koyano, Localization of Integrin Beta-4 Subunit at Soft Tissue-Titanium or Zirconia Interface., Journal of clinical medicine, 10.3390/jcm9103331, 9, 10, 2020.10, Currently, along with titanium (Ti), zirconia is widely used as an abutment material for dental implants because it makes it possible to avoid gingival discoloration; however, the epithelial sealing capability of zirconia remains unknown. The purpose of the present study is to elucidate the localization of integrin β4 subunit (Inβ4), one of the main proteins in the attachment structure between gingival junctional epithelial (JE) cells and substrata. Maxillary first molars were extracted from rats, and implants were placed with Ti or zirconia transgingival parts; then, the localization of Inβ4 was observed. Morphological and functional changes in rat oral epithelial cells (OECs) cultured on a culture dish (Dish) and Ti and zirconia plates were also evaluated with Inβ4 immunofluorescence histochemistry and Western blotting. After four weeks of implant placement, the morphology of the peri-implant epithelium (PIE) and the localization of Inβ4 around the Ti and zirconia transgingival parts were similar. However, both exhibited markedly shorter Inβ4-positive bands in the PIE than in the JE around natural teeth. Decreased expression levels of Inβ4 were observed in OECs cultured on Ti and zirconia plates compared with those cultured on Dish. In conclusion, although inferior to natural teeth, zirconia implants are thought to have epithelial sealing properties comparable to those of titanium..
27. 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
28. 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..
29. 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..
30. 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..
31. 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 & gerontology international, 10.1111/ggi.13911, 20, 6, 607-614, 2020.06, 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 
32. 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..
33. 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, 5620-5620, 2020.03, 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..
34. 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..
35. 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..
36. 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..
37. 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 (60N). Among the three experimental groups, those receiving 40N 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 40N group, implying existence of a loading threshold for peri-implant bone formation and resorption..
38. 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 & engineering, 10.1021/acsbiomaterials.9b00499, 5, 10, 4976-4984, 2019.10, 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..
39. 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 & 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..
40. 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..
41. 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..
42. 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 (Basel, Switzerland), 10.3390/ma12172748, 12, 17, 2019.08, 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 β4, 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..
43. Ikiru Atsuta, 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, 107, 7, 1379-1385, 2019.07, 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. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019..
44. 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, 2019.07, 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..
45. 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..
46. 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. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 815-827, 2019..
47. 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..
48. 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..
49. 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..
50. 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..
51. 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..
52. 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..
53. Haomiao Zhang, Yasuko Moriyama, Yasunori Ayukawa, Yunia Dwi Rakhmatia, Yoko Tomita, 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..
54. Yasunori Ayukawa, The Influence Of Topographical And Chemical Properties Of Dental Implants On Soft Tissue Integration., Journal of Indian Prosthodontic Society, 10.4103/0972-4052.244585, 18, Suppl 1, S5, 2018.10.
55. Urata Mariko, Kokabu Shoichiro, Matsubara Takuma, Sugiyama Goro, Nakatomi Chihiro, Takeuchi Hiroshi, Hirata-Tsuchiya Shizu, Aoki Kazuhiro, Tamura Yukihiko, Moriyama Yasuko, Ayukawa Yasunori, Matsuda Miho, Zhang Min, Koyano Kiyoshi, Kitamura Chiaki, Jimi Eijiro, A peptide that blocks the interaction of NF-B p65 subunit with Smad4 enhances BMP2-induced osteogenesis, JOURNAL OF CELLULAR PHYSIOLOGY, 10.1002/jcp.26571, 233, 9, 7356-7366, 2018.09.
56. 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..
57. Yunia Dwi Rakhmatia, Yasunori Ayukawa, Akihiro Furuhashi, Kiyoshi Koyano, Carbonate Apatite Containing Statin Enhances Bone Formation in Healing Incisal Extraction Sockets in Rats., Materials (Basel, Switzerland), 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..
58. 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, 2018.07, 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..
59. 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.
60. 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.
61. 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.
62. Katsuhiro Tsuruta, Yasunori Ayukawa, Tatsuya Matsuzaki, Masafumi Kihara, Kiyoshi Koyano, The influence of implant-abutment connection on the screw loosening and microleakage., International journal of implant dentistry, 10.1186/s40729-018-0121-y, 4, 1, 11-11, 2018.04, BACKGROUND: There are some spaces between abutment and implant body which can be a reservoir of toxic substance, and they can penetrate into subgingival space from microgap at the implant-abutment interface. This penetration may cause periimplantitis which is known to be one of the most important factors associated with late failure. In the present study, three kinds of abutment connection system, external parallel connection (EP), internal parallel connection (IP), and internal conical connection (CC), were studied from the viewpoint of microleakage from the gap between the implant and the abutment and in connection with the loosening of abutment screw. METHODS: We observed dye leakage from abutment screw hole to outside through microgap under the excessive compressive and tensile load and evaluated the anti-leakage characteristics of these connection systems. RESULTS: During the experiment, one abutment screw for EP and two screws for IP, out of seven samples in each group, were fractured. After the 2000 cycles of compressive tensile loadings, removal torque value (RTV) of abutment screw represented no statistical differences among three groups. Standard deviation was largest in the RTV of EP and smallest in that of CC. The results of microleakage of toluidine blue from implant-abutment connection indicated that microleakage generally increased as loading procedure progressed. The amount of microleakage was almost plateau at 2000 cycles in CC, but still increasing in other two groups. The value of microleakage greatly scattered in EP, but the deviation of that in CC is significantly smaller. At 500 cycles of loading, there were no significant differences in the amount of microleakage among the groups, but at 1000, 1500, and 2000 cycles of loading, the amount of microleakage in CC was significantly smaller than that in IP. Throughout the experiment, the amount of microleakage in EP was largest, but no statistical difference was indicated due to the high standard deviation. CONCLUSIONS: Within the limitation of the present study, CC was stable even after the loading in the RTV of abutment screw and it prevented microleakage from the microgap between the implant body and the abutment, among the three tested connections..
63. 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.
64. 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.
65. 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..
66. 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..
67. Miya Kanazawa, Ikiru Atsuta, Yasunori Ayukawa, Takayoshi Yamaza, Ryosuke Kondo, Yuri Matsuura, Kiyoshi Koyano, The influence of systemically or locally administered mesenchymal stem cells on tissue repair in a rat oral implantation model., International journal of implant dentistry, 10.1186/s40729-017-0112-4, 4, 1, 2-2, 2018.01, BACKGROUND: Multipotent mesenchymal stem cells (MSCs) are used clinically in regenerative medicine. Our previous report showed systemically injected MSCs improved peri-implant sealing and accelerated tissue healing. However, the risks of systemic MSC administration, including lung embolism, must be considered; therefore, their local application must be assessed for clinical safety and efficacy. We investigated differences in treatment effect between local and systemic MSC application using a rat oral implantation model. METHODS: Rat bone marrow-derived MSCs were isolated and culture-expanded. The rat's right maxillary first molars were extracted and replaced with experimental titanium implants. After 24 h, MSCs (1 × 106/ml) were systemically or locally injected into recipient rats via the tail vein (systemic group) or buccal subcutaneous tissue (local group), respectively. Rats treated in the absence of MSCs were included as a control (control group). The maxillary epithelium was assessed histologically after 4 weeks to evaluate laminin-332 (Ln-332) distribution and horseradish peroxidase invasion, as indicators of peri-implant epithelium (PIE) formation and PIE sealing to the implant surface, respectively. The effect of MSCs on rat oral epithelial cell (OEC) morphology was determined by coculture. RESULTS: Systemic group MSCs accumulated early at the peri-implant mucosa, while local group MSCs were observed in various organs prior to later accumulation around the implant surface. PIE formation and Ln-332-positive staining at the implant interface were enhanced in the systemic group compared with the local and control groups. Furthermore, OEC adherence on implants was reduced in high-density compared with low-density MSC cocultures. CONCLUSIONS: Local MSC injection was more ineffective than systemic MSC injection at enhancing PIE sealing around titanium implants. Thus, although local MSC administration has a wide range of applications, further investigations are needed to understand the exact cellular and molecular mechanisms of this approach prior to clinical use..
68. 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..
69. 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. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2465-2475, 2017..
70. 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 mu m in pore diameter) or commercially available macro-porous titanium mesh (1700 mu m 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 (mm(3)), percentage of new bone volumes in the total defect volumes (bone ratio: %), and new bone area (mm(2)) through morphometric evaluation were found on the novel membranes with 50-mu m-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-mu m-diameter pores were effective for guided bone regeneration in the early stage of healing..
71. 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..
72. 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..
73. 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.
74. 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, 10.1016/j.jpor.2016.01.004, 60, 4, 229-230, 2016.10.
75. 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.
76. 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..
77. Matsuura Y, Atsuta I, Ayukawa Y, Yamaza T, Kondo R, Takahashi A, Ueda N, Oshiro W, Tsukiyama Y, Koyano K, Therapeutic interactions between mesenchymal stem cells for healing medication-related osteonecrosis of the jaw., Stem cell research & therapy, 10.1186/s13287-016-0367-3, 7, 1, 119-119, 2016.08.
78. Shimizu H, Jinno Y, Ayukawa Y, Atsuta I, Arahira T, Todo M, Koyano K, Tissue Reaction to a Novel Bone Substitute Material Fabricated With Biodegradable Polymer-Calcium Phosphate Nanoparticle Composite., Implant dentistry, 10.1097/ID.0000000000000447, 25, 5, 567-574, 2016.08.
79. State-of-the-art of the Surface Modification of Oral Implants.
80. Atsuta I, Ayukawa Y, Kondo R, Oshiro W, Matsuura Y, Furuhashi A, Tsukiyama Y, Koyano K, Soft tissue sealing around dental implants based on histological interpretation., Journal of prosthodontic research, 10.1016/j.jpor.2015.07.001, 60, 1, 3-11, 2016.01.
81. "Occlusal consideration for fixed implant prosthesis in mandibular posterior region"
Clinical guidelines or definitive criteria for "Occlusal consideration for fixed implant prosthesis in mandibular posterior region" have not been established yet although the dental implant is an essential treatment option for current prosthetic dentistry. This position paper aimed to propose a critical recommendation and consequently indicate a tentative practice guideline. In this paper, the first and second molar missing in the mandible was assumed as the most typical partial edentulous jaw. A panel of clinical experts concerning dental implant practice was selected from the members of the Japan Prosthodontic Society, and a meeting was held to collect clinical data obtained from daily practice and to estimate expert opinions. As a result, general remarks were presented regarding shapes of prostheses, position and number of occlusal contact points, occlusal contact during lateral excursion, displacement of periodontal ligament, and materials of occlusal surface. However, the expert opinions described above have not been supported by clinical evidence. Moreover, neither the effect of those therapies nor long-term prognosis has been thoroughly investigated. Thus, further study for collecting the clinical evidences is required to formulate the clinical guideline..
82. 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.
83. 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.
84. Yasunami N, Ayukawa Y, Furuhashi A, Atsuta I, Rakhmatia YD, Moriyama Y, Masuzaki T, Koyano K, 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 (Bristol, England), 10.1088/1748-6041/11/1/015001, 11, 1, 15001-015001, 2015.12.
85. Tanaka H, Toyoshima T, Atsuta I, Ayukawa Y, Sasaki M, Matsushita Y, Hiraoka R, Koyano K, Nakamura S, 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, 2015.12.
86. 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.
87. 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.
88. Toyoshima T, Tanaka H, Ayukawa Y, Howashi M, Masuzaki T, Kiyosue T, Koyano K, Nakamura S, Primary Stability of a Hybrid Implant Compared with Tapered and Cylindrical Implants in an Ex Vivo Model., Clinical implant dentistry and related research, 10.1111/cid.12205, 17, 5, 950-956, 2015.10.
89. 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.
90. 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.
91. Oshiro W, Ayukawa Y, Atsuta I, Furuhashi A, Yamazoe J, Kondo R, Sakaguchi M, Matsuura Y, Tsukiyama Y, Koyano K, Effects of CaCl2 hydrothermal treatment of titanium implant surfaces on early epithelial sealing., Colloids and surfaces. B, Biointerfaces, 10.1016/j.colsurfb.2015.04.025, 131, 141-147, 2015.04.
92. 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..
93. 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.
94. 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.
95. Yoichiro Ogino, Yasunori Ayukawa, Yoko TOMITA, Kiyoshi Koyano, Prosthetic aspects in adult osteoporosis, Journal of Prosthetic Dentistry, 2014.10.
96. 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.
97. Yoichiro Ogino, Yasunori Ayukawa, Yoko Tomita, Kiyoshi Koyano, PROSTHETIC ASPECTS IN ADULT OSTEOPETROSIS, JOURNAL OF PROSTHETIC DENTISTRY, 10.1016/j.prosdent.2014.04.007, 112, 4, 736-740, 2014.10, Osteopetrosis (OP) is a rare condition characterized by skeletal sclerosis caused by dysfunctional osteoclasts. Though many reports have described severe infantile-malignant autosomal recessive OP, few have described the prosthetic management of adult OP. This report discusses the prosthetic treatment of adult OP. Although prosthodontists should try to reconstruct occlusal function as much as possible, a conservative prosthodontic approach may be a reasonable and recommended treatment option for minimizing the risk of further osteomyelitis and osteonecrosis..
98. Howashi M, Tsukiyama Y, Ayukawa Y, Isoda-Akizuki K, Kihara M, Imai Y, Sogo M, Koyano K, 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 and related research, 10.1111/cid.12261, 18, 1, 107-16, 2014.09.
99. Yunia Dwi Rakhmatia, Yasunori Ayukawa, Akihiro Furuhashi, Kiyoshi Koyano, Microcomputed Tomographic and Histomorphometric Analyses of Novel Titanium Mesh Membranes for Guided Bone Regeneration: A Study in Rat Calvarial Defects, INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS, 10.11607/jomi.3219, 29, 4, 826-835, 2014.07, Purpose: The objective of this study was to evaluate the optimal thickness and porosity of novel titanium mesh membranes to enhance bone augmentation, prevent soft tissue ingrowth, and prevent membrane exposure. Materials and Methods: Six types of novel titanium meshes with different thicknesses and pore sizes, along with three commercially available membranes, were used to cover surgically created calvarial defects in 6-week-old Sprague-Dawley rats. The animals were killed after 4 or 8 weeks. Microcomputed tomographic analyses were performed to analyze the three-dimensional bone volume and bone mineral density. Soft tissue ingrowth was also evaluated histologically and histomorphometrically. Results: The novel titanium membranes used in this study were as effective at augmenting bone in the rat calvarial defect model as the commercially available membranes. The greatest bone volume was observed on 100-mu m-thick membranes with larger pores, although these membranes promoted growth of bone with lower mineral density. Soft tissue ingrowth when 100-mu m membranes were used was increased at 4 weeks but decreased again by 8 weeks to a level not statistically significantly different from other membranes. Conclusion: Membrane thickness affects the total amount of new bone formation, and membrane porosity is an essential factor for guided bone regeneration, especially during the initial healing period, although the final bone volume obtained is essentially the same. Newly developed titanium mesh membranes of 100 mu m in thickness and with large pores appear to be optimal for guided bone regeneration..
100. 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.
101. 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, 10.1016/j.jpor.2013.11.001, 58, 2, 127-131, 2014.04, Patients: Dental implant treatment in patients with complicated systemic disease has been discussed, especially in the context of achieving osseointegration. However, some patients with no pre-existing systemic disease develop it later, during their implant maintenance periods. Organ transplants, and the lifelong administration of immunosuppressants that follows, are also of relevance to post-implant oral health. Thus, strategies to maintain the health of pen-implant tissue in these patients should be considered. Here, we present the case of a patient receiving a living-donor lung transplant during her implant follow-up period. The condition of the lung is affected by that of the oral cavity, so the maintenance is of utmost importance. Throughout the follow-up period, we provided periodical professional maintenance care.
Discussion and conclusion: The patient experienced no complications, alterations in her radiographic findings, or worsening of periodontal indices, despite being extensively medicated with immunosuppressants, steroids and bisphosphonate. (C) 2013 Japan Prosthodontic Society. Published by Elsevier Ireland. All rights reserved..
102. 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.
103. 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.
104. Rakhmatia YD, Ayukawa Y, Atsuta I, Furuhashi A, Koyano K, Fibroblast attachment onto novel titanium mesh membranes for guided bone regeneration., Odontology / the Society of the Nippon Dental University, 10.1007/s10266-014-0151-8, 103, 2, 218-226, 2014.03.
105. 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, 10.1038/labinvest.2013.152, 94, 3, 286-296, 2014.03, Mesenchymal stem cells (MSCs) have potential to differentiate into multiple cell lineages. Recently, it was shown that MSCs also have anti-inflammatory and immunomodulatory functions. In this report, we investigated the regulatory function of MSCs in the development of inflammatory bone destruction in rats with adjuvant-induced arthritis (AA rats). MSCs were isolated from rat bone marrow tissues, expanded in the presence of basic FGF, and intraperitoneally injected into AA rats. MSC administration significantly suppressed inflammatory parameters: swelling score, swelling width, and thickness of hind paw. Radiographic evaluation indicated that MSC significantly suppressed bone destruction. Histological analysis showed that administration of MSCs markedly suppressed osteoclastogenesis in AA rats. To further delineate their effects on osteoclastogenesis, MSCs were added to in vitro bone marrow cultures undergoing osteoclastogenesis. MSCs significantly suppressed osteoclastogenesis in this system. Chemokine receptor expression in MSCs was assessed by RT-PCR, and a chemotactic assay was performed using a transwell culture system. MSCs showed significant chemotaxis to MIP-1 alpha (CCL3) and SDF-1 alpha (CXCL12), chemokines preferentially expressed in the area of inflammatory bone destruction. Furthermore, MSCs expressed IL-10 and osteoprotegerin, cytokines that suppress osteoclastogenesis. These data suggest that recruitment of MSC to the area of bone destruction in AA rats could suppress inflammatory bone destruction and raise the possibility that MSCs may have potential for the treatment of inflammatory bone destruction in arthritis..
106. 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.
107. 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, 24, 12, 1310-1315, 2013.12, Objectives: To investigate bacterial adhesion to various abutment materials. Material and methods: Thirty volunteers participated in this study. Resin splints were fabricated, and five types of disks were fabricated from pure titanium, gold-platinum alloy, zirconia, alumina, and hydroxyapatite with uniform surface roughness and attached to the buccal surface of each splint. After 4 days of use by the subjects, the plaque accumulated on the disk surfaces was analyzed. The bacterial community structure was evaluated using 16S rRNA gene profiling with terminal restriction fragment length polymorphism analysis. The total bacterial count on each disk was estimated using quantitative polymerase chain reaction. Results: Terminal restriction fragment length polymorphism profiles were more similar between tested materials than between subjects, suggesting that the bacterial community structures on the abutment material were influenced more by the individuals than by the type of material. However, the total number of bacteria attached to a disk was significantly different among five materials (P 
108. 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.
109. Atsuta I, Ayukawa Y, Yamaza T, Furuhashi A, Koyano K, The role of phosphoinositide 3-kinase in adhesion of oral epithelial cells to titanium., Archives of oral biology, 10.1016/j.archoralbio.2013.07.013, 58, 11, 1696-1708, 2013.11.
110. Atsuta I, Ayukawa Y, Yamaza T, Furuhashi A, Koyano K, The role of phosphoinositide 3-kinase in adhesion of oral epithelial cells to titanium., Archives of oral biology, 10.1016/j.archoralbio.2013.07.013, 58, 11, 1696-1708, 2013.11.
111. 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.
112. ATSUTA IKIRU, AYUKAWA Yasunori, Furuhashi Akihiko, Yamaza Takayoshi, TSUKIYAMA Yoshihiro, KOYANO Kiyoshi, Promotive effect of insulin-like growth factor-1 for epithelial sealing to titanium implants, J Biomed Mater Res A, 10.1002/jbm.a.34608, 101, 10, 2896-2904, 2013.10.
113. ATSUTA IKIRU, AYUKAWA Yasunori, Furuhashi Akihiko, Yamaza Takayoshi, TSUKIYAMA Yoshihiro, KOYANO Kiyoshi, Promotive effect of insulin-like growth factor-1 for epithelial sealing to titanium implants, J Biomed Mater Res A, 10.1002/jbm.a.34608, 101, 10, 2896-2904, 2013.10.
114. Bone regeneration of tibial defects in rats with enzymatic hydrogelation of gelatin derivative and recombinant human platelet-derived growth factor-BB complex..
115. 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.
116. 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.
117. Takahashi A, Kukita A, Li YJ, Zhang JQ, Nomiyama H, Yamaza T, Ayukawa Y, Koyano K, Kukita T, Tunneling nanotube formation is essential for the regulation of osteoclastogenesis., Journal of cellular biochemistry, 10.1002/jcb.24433, 114, 6, 1238-1247, 2013.06.
118. Takahashi A, Kukita A, Li YJ, Zhang JQ, Nomiyama H, Yamaza T, Ayukawa Y, Koyano K, Kukita T, Tunneling nanotube formation is essential for the regulation of osteoclastogenesis., Journal of cellular biochemistry, 10.1002/jcb.24433, 114, 6, 1238-1247, 2013.06.
119. 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.
120. 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.
121. ATSUTA IKIRU, AYUKAWA Yasunori, Furuhashi Akihiko, OGINO YOICHIRO, Moriyama Yasuko, Tsukiyama Yoshihiro, Koyano Kiyoshi, In Vivo and In Vitro Studies of Epithelial Cell Behavior around Titanium Implants with Machined and Rough Surfaces, Clin Implant Dent Relat Res, 10.1111/cid.12043, 16, 5, 772-81, 2013.02.
122. ATSUTA IKIRU, AYUKAWA Yasunori, Furuhashi Akihiko, OGINO YOICHIRO, Moriyama Yasuko, Tsukiyama Yoshihiro, Koyano Kiyoshi, In Vivo and In Vitro Studies of Epithelial Cell Behavior around Titanium Implants with Machined and Rough Surfaces, Clin Implant Dent Relat Res, 10.1111/cid.12043, 16, 5, 772-81, 2013.02.
123. Rakhmatia YD, Ayukawa Y, Furuhashi A, Koyano K, Current barrier membranes: titanium mesh and other membranes for guided bone regeneration in dental applications., Journal of prosthodontic research, 10.1016/j.jpor.2012.12.001, 57, 1, 3-14, 2013.01.
124. 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, 1-4, 27-27, 2012.12.
125. 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, 1-4, 27-27, 2012.12.
126. 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.
127. Daisuke Esaki, Yasuyuki Matsushita, Yasunori Ayukawa, Nobuo Sakai, Yoshinori Sawae, Kiyoshi Koyano, Relationship between magnitude of immediate loading and peri-implant osteogenesis in dogs, CLINICAL ORAL IMPLANTS RESEARCH, 10.1111/j.1600-0501.2011.02305.x, 23, 11, 1290-1296, 2012.11, Objectives The purpose of this study was to investigate the influence of the magnitude of immediate loading on peri-implant bone in an animal model of dental implantation. Material and methods Eight weeks after the extraction of maxillary and mandibular premolars, three implants were inserted bilaterally in the mandibles of six Beagle dogs. One implant was unloaded (UL) as a control, and two implants were loaded immediately with 10N (mild loading: ML) or 50N (excessive loading: EL) laterally using a cyclic loading device twice a week for 3weeks. Fluorescent bone markers were injected to examine bone formation around the implants. The animals were sacrificed 3weeks after implantation. Peri-implant osteogenesis was assessed by histomorphometric procedures, i.e., measuring bone-implant contact (BIC) and bone density (BD). Results The UL and ML groups had no peri-implant infection, and newly formed bone was observed over a wide area from the implant neck toward the tip, and in direct contact with the implant surface. In contrast, in the EL group, newly formed bone was rarely observed around the implant neck and there were signs of infection. Both BIC and BD in the ML group were significantly greater than those in the other groups. BIC and BD in the EL group were significantly lower than those in the other groups. Conclusion A suitable magnitude of load applied immediately after dental implantation promotes peri-implant osteogenesis..
128. Daisuke Esaki, Yasuyuki Matsushita, Yasunori Ayukawa, Nobuo Sakai, Yoshinori Sawae, Kiyoshi Koyano, Relationship between magnitude of immediate loading and peri-implant osteogenesis in dogs, CLINICAL ORAL IMPLANTS RESEARCH, 10.1111/j.1600-0501.2011.02305.x, 23, 11, 1290-1296, 2012.11, Objectives The purpose of this study was to investigate the influence of the magnitude of immediate loading on peri-implant bone in an animal model of dental implantation. Material and methods Eight weeks after the extraction of maxillary and mandibular premolars, three implants were inserted bilaterally in the mandibles of six Beagle dogs. One implant was unloaded (UL) as a control, and two implants were loaded immediately with 10N (mild loading: ML) or 50N (excessive loading: EL) laterally using a cyclic loading device twice a week for 3weeks. Fluorescent bone markers were injected to examine bone formation around the implants. The animals were sacrificed 3weeks after implantation. Peri-implant osteogenesis was assessed by histomorphometric procedures, i.e., measuring bone-implant contact (BIC) and bone density (BD). Results The UL and ML groups had no peri-implant infection, and newly formed bone was observed over a wide area from the implant neck toward the tip, and in direct contact with the implant surface. In contrast, in the EL group, newly formed bone was rarely observed around the implant neck and there were signs of infection. Both BIC and BD in the ML group were significantly greater than those in the other groups. BIC and BD in the EL group were significantly lower than those in the other groups. Conclusion A suitable magnitude of load applied immediately after dental implantation promotes peri-implant osteogenesis..
129. 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.
130. 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.
131. 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.
132. 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., Clin Oral Implants Res, 10.1111/j.1600-0501.2011.02203.x, 23, 7, 832-826, 2012.07.
133. Furuhashi A, Ayukawa Y, Atsuta I, Okawachi H, Koyano K, The difference of fibroblast behavior on titanium substrata with different surface characteristics., Odontology / the Society of the Nippon Dental University, 10.1007/s10266-011-0029-y, 100, 2, 199-205, 2012.07.
134. 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., Clin Oral Implants Res, 10.1111/j.1600-0501.2011.02203.x, 23, 7, 832-826, 2012.07.
135. Furuhashi A, Ayukawa Y, Atsuta I, Okawachi H, Koyano K, The difference of fibroblast behavior on titanium substrata with different surface characteristics., Odontology / the Society of the Nippon Dental University, 10.1007/s10266-011-0029-y, 100, 2, 199-205, 2012.07.
136. 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.
137. 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.
138. 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.
139. Atsuta I, Ayukawa Y, Ogino Y, Moriyama Y, Jinno 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.
140. 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.
141. 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.
142. 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.
143. 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 properties: a rodent study., Acta biomaterialia, 10.1016/j.actbio.2009.10.045, 6, 4, 1610-1618, 2010.04.
144. 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, 10.1016/j.biomaterials.2010.01.016, 31, 12, 3327-3334, 2010.04.
145. 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, J Oral Rehabil, 10.1111/j.1365-2842.2009.02011.x, 37, 2, 123-130, 2010.02.
146. 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, J Oral Rehabil, 10.1111/j.1365-2842.2009.02011.x, 37, 2, 123-130, 2010.02.
147. 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.
148. Moriyama Y, Ayukawa Y, Kabemura K, Matsushita Y, Kihara M, Tsukiyama Y, Todo M, Takao Y, Koyano K, The alternation of peri-implant bone response exposed to static lateral load, J Biomech Sci Eng, 10.1299/jbse.4.326, 4, 3, 326-335, 2009.09.
149. Moriyama Y, Ayukawa Y, Kabemura K, Matsushita Y, Kihara M, Tsukiyama Y, Todo M, Takao Y, Koyano K, The alternation of peri-implant bone response exposed to static lateral load, J Biomech Sci Eng, 10.1299/jbse.4.326, 4, 3, 326-335, 2009.09, In the present study, peri-implant tissue alteration was studied histologically, and then differences in the gene expression pattern of certain proteins were analyzed using cDNA microarray analysis, under the influence of static lateral load. Beagle dogs were divided into two groups: control and load. Three months after the extraction of mandibular premolars, two implants were placed in each side of the mandible. Each group was further divided into subgroups for loading times of 1, 7 and 14 days. Immediately after the implant installation, a loading device was adhered between the abutments of neighboring implants. Afterward, the expansion screw of the load group was activated by 360-degree rotation, resulting in 0.7 mm horizontal expansion. After sacrificing the dogs, peri-implant tissue was collected, then microarray analysis for the detection of gene expression was performed, as well as histology. Histology indicated that the peri-implant tissue broke down under the influence of the load. Microarray analysis demonstrated the presence of load-sensitive gene expression even after 1 day. Differences in gene expression patterns in concert with static lateral load were demonstrated, even at an early stage post-operation. Further study may help in the diagnosis of pathological overload..
150. 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.
151. 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.
152. 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.
153. 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.
154. 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.
155. 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.
156. 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.
157. Akira Okamura, Yasunori Ayukawa, Shinji Iyama, Kiyoshi Koyano, Effect of the difference of bone turnover on peri-titanium implant osteogenesis in ovariectomized rats., Journal of biomedical materials research. Part A, 70, 3, 497-505, 2004.09, High and low bone turnover situations, both of which are typically observed as postmenopausal and senile osteoporosis, were created by ovariectomy (OVX), and then an investigation of whether or not the difference of bone turnover affected peri-titanium (Ti) implant osteogenesis in rats was conducted. Female rats were divided into four groups. The experimental and control groups underwent OVX or sham operations at 15 or 27 weeks of age, as high or low bone turnover groups, respectively. Ti implants were inserted into the tibiae at 30 weeks, then fluorochromes were injected 10 or 20 days after the implantation for histometry. The implants were retained for 30 days and then ground sections were prepared. Afterward, the cortical bone growth rate, bone contact ratio (BCR) of the implant in both the cortical bone area and medullary canal area, and the average trabecular bone thickness around the implant were evaluated. Biochemical markers of bone turnover were also measured. Biochemical measurements indicated both increasing osteocalcin production in OVX rats and decreasing tartrate-resistant acid phosphatase activity in the low-turnover group. Histometrical measurements showed decreasing cortical growth and low BCR in the medullary canal of the low-turnover group. The high-turnover group demonstrated BCR as high as that of the control group. There was no significant difference in the average trabecular bone thickness around the implant among the groups. As a result, two types of osteoporotic situations were confirmed and it was shown that the difference of bone turnover was clearly due to the diverse osteogenesis around the Ti implant..
158. Akira Okamura, Yasunori Ayukawa, Shinji Iyama, Kiyoshi Koyano, Effect of the difference of bone turnover on peri-titanium implant osteogenesis in ovariectomized rats., Journal of biomedical materials research. Part A, 70, 3, 497-505, 2004.09, High and low bone turnover situations, both of which are typically observed as postmenopausal and senile osteoporosis, were created by ovariectomy (OVX), and then an investigation of whether or not the difference of bone turnover affected peri-titanium (Ti) implant osteogenesis in rats was conducted. Female rats were divided into four groups. The experimental and control groups underwent OVX or sham operations at 15 or 27 weeks of age, as high or low bone turnover groups, respectively. Ti implants were inserted into the tibiae at 30 weeks, then fluorochromes were injected 10 or 20 days after the implantation for histometry. The implants were retained for 30 days and then ground sections were prepared. Afterward, the cortical bone growth rate, bone contact ratio (BCR) of the implant in both the cortical bone area and medullary canal area, and the average trabecular bone thickness around the implant were evaluated. Biochemical markers of bone turnover were also measured. Biochemical measurements indicated both increasing osteocalcin production in OVX rats and decreasing tartrate-resistant acid phosphatase activity in the low-turnover group. Histometrical measurements showed decreasing cortical growth and low BCR in the medullary canal of the low-turnover group. The high-turnover group demonstrated BCR as high as that of the control group. There was no significant difference in the average trabecular bone thickness around the implant among the groups. As a result, two types of osteoporotic situations were confirmed and it was shown that the difference of bone turnover was clearly due to the diverse osteogenesis around the Ti implant..
159. 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.
160. 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.
161. 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.
162. Dental Implant-bone Interface -Influence of the Surface Geometry-.
163. F Takeshita, K Murai, S Iyama, Y Ayukawa, T Suetsugu, Uncontrolled diabetes hinders bone formation around titanium implants in rat tibiae. A light and fluorescence microscopy, and image processing study, JOURNAL OF PERIODONTOLOGY, 69, 3, 314-320, 1998.03, THIS STUDY EXAMINED THE INFLUENCE of diabetes mellitus on bone formation around cylindrical titanium (Ti) implants (1.0 mm in diameter and 1.5 mm in length) inserted transcortically and extending into the medullary canal of rat tibiae using light and fluorescence microscopies and image processing. Forty-eight male Wistar King A rats (age 5 weeks) were used in this experiment. Streptozotocin was injected intraperitoneally to induce diabetes and the serum glucose concentration was checked to ensure the induction of diabetes prior to implant placement and at the time of sacrifice. The animals were sacrificed 7, 28, 56, or 84 days after placement. Toluidine blue-stained undecalcified sections were prepared for histological observation and image analysis. The Ti implants in the control group became increasingly encapsulated with a bone layer. The implants in the diabetes-induced (DI) group were also surrounded with a thin bone layer. Abundant adipocytes were observed in the DI group as compared with the control group. Quantitative evaluation indicated that the control group showed a significantly higher percent of bone contact, and thickness of surrounding bone and area than the DI group. Consequently, the present study suggests that uncontrolled diabetes would hinder bone formation around Ti implants in rats..
164. F Takeshita, K Murai, S Iyama, Y Ayukawa, T Suetsugu, Uncontrolled diabetes hinders bone formation around titanium implants in rat tibiae. A light and fluorescence microscopy, and image processing study, JOURNAL OF PERIODONTOLOGY, 69, 3, 314-320, 1998.03, THIS STUDY EXAMINED THE INFLUENCE of diabetes mellitus on bone formation around cylindrical titanium (Ti) implants (1.0 mm in diameter and 1.5 mm in length) inserted transcortically and extending into the medullary canal of rat tibiae using light and fluorescence microscopies and image processing. Forty-eight male Wistar King A rats (age 5 weeks) were used in this experiment. Streptozotocin was injected intraperitoneally to induce diabetes and the serum glucose concentration was checked to ensure the induction of diabetes prior to implant placement and at the time of sacrifice. The animals were sacrificed 7, 28, 56, or 84 days after placement. Toluidine blue-stained undecalcified sections were prepared for histological observation and image analysis. The Ti implants in the control group became increasingly encapsulated with a bone layer. The implants in the diabetes-induced (DI) group were also surrounded with a thin bone layer. Abundant adipocytes were observed in the DI group as compared with the control group. Quantitative evaluation indicated that the control group showed a significantly higher percent of bone contact, and thickness of surrounding bone and area than the DI group. Consequently, the present study suggests that uncontrolled diabetes would hinder bone formation around Ti implants in rats..
165. 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)41:13.0.CO;2-Q, 41, 1, 111-119, Vol.41,pp.111-119, 1998.01.
166. 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.
167. 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.
168. F Takeshita, S Iyama, Y Ayukawa, T Suetsugu, M Oishi, Abscess formation around a hydroxyapatite-coated implant placed into the extraction socket with autogenous bone graft. A histological study using light microscopy, image processing, and confocal laser scanning microscopy, JOURNAL OF PERIODONTOLOGY, 68, 3, 299-305, 1997.03, THE PURPOSE OF THIS STUDY was to evaluate the radiologic, histologic, and histometric findings for a retrieved hydroxyapatite (HA)-coated implant which had been placed into a fresh extraction socket with autogenous bone graft 3 months previously. A periapical radiograph disclosed a vertical bone loss around the implant cervix. Examination of histologic sections disclosed that granulation tissue including bone chips around the cervix, and newly-formed bone tissue around the grafted bone tissue on the HA coated surface. In the confocal laser scanning microscopic findings toluidine blue-negative bone tissue showed autofluorescence. Histometric analysis indicated that the average percent bone contact was 29.2% (ranged 26.4% to 34.1%). Suspected reasons for failure were an early exposure of the barrier membrane, its early removal, the implant placement into an infected site, inadequate antibiotic premedication, and/or poor control of infections around teeth prior to implant surgery and around implants before and after placement of barrier membrane..
169. F Takeshita, S Iyama, Y Ayukawa, T Suetsugu, M Oishi, Abscess formation around a hydroxyapatite-coated implant placed into the extraction socket with autogenous bone graft. A histological study using light microscopy, image processing, and confocal laser scanning microscopy, JOURNAL OF PERIODONTOLOGY, 68, 3, 299-305, 1997.03, THE PURPOSE OF THIS STUDY was to evaluate the radiologic, histologic, and histometric findings for a retrieved hydroxyapatite (HA)-coated implant which had been placed into a fresh extraction socket with autogenous bone graft 3 months previously. A periapical radiograph disclosed a vertical bone loss around the implant cervix. Examination of histologic sections disclosed that granulation tissue including bone chips around the cervix, and newly-formed bone tissue around the grafted bone tissue on the HA coated surface. In the confocal laser scanning microscopic findings toluidine blue-negative bone tissue showed autofluorescence. Histometric analysis indicated that the average percent bone contact was 29.2% (ranged 26.4% to 34.1%). Suspected reasons for failure were an early exposure of the barrier membrane, its early removal, the implant placement into an infected site, inadequate antibiotic premedication, and/or poor control of infections around teeth prior to implant surgery and around implants before and after placement of barrier membrane..
170. Histopathologic Observations of Tissue Reaction to Three Kinds of Membrane Placed on the Bone Defects around Implants
The purpose of this study was to investigate the tissue reaction to three kinds of membranes, Gore-Tex Augmentation Material (GTAM), Vicryl, and Dura Mater, placed on bone defects around the titanium implants. Nine adult dogs weighing 15kg were used in this study. The dogs were sacrificed either 2, 4, or 12 weeks after placement. Vicryl was exposed 2 weeks after placement. Histologically, it was found that Vicryl was completely resorbed, Dura Mater was replaced with connective tissue at 12 weeks, and bone defects using GTAM and Dura Mater but not Vicryl were partially filled with newly-formed bone tissue. Active bone formation was observed in the space between membranes and pre-existing bone tissue..
171. F Takeshita, S Iyama, Y Ayukawa, H Akedo, T Suetsugu, Study of bone formation around dense hydroxyapatite implants using light microscopy, image processing and confocal laser scanning microscopy, BIOMATERIALS, 18, 4, 317-322, 1997.02, The bone reaction to hydroxyapatite (HA) implants inserted transcortically and extending into the medullary canal of rat tibiae was quantitatively assessed using light microscopy, confocal laser scanning microscopy and an image processing system. Sixty-five male rats (6 weeks old) were divided into two groups, 60 for histological observation and image analysis and five for time-labelling. In the histological observation, control sections of 168 days showed a few bone trabeculae in the fatty bone marrow, and Ti implants had become gradually encapsulated with a thick bone tissue layer; however, HA implants became almost completely encapsulated with a thin bone tissue layer during the 168 day experimental period. Histometrical analysis of the percent bone contact revealed that Ti implants showed a continuous increasing curve, and HA implants showed rapid increase in the initial healing period up to 14 days, with 96% bone contact reaching a plateau at 84 days after operation. There was a significant difference in the percent of bone contact between Ti and HA implants throughout the experimental period. Confocal laser scanning microscopic observations revealed the presence of calcein at the 14th day and only slight alizarin colour layer in the bone tissue at the 28th day, both indicating bone formation. These findings suggest that the activity of bone formation was higher at the 14th day than at the 28th day. Also, the percentage of bone contact of HA is superior to titanium throughout the experimental period, and the ascending patterns of both implants are quite different to each other. (C) 1997 Elsevier Science Limited. All rights reserved..
172. F Takeshita, S Iyama, Y Ayukawa, H Akedo, T Suetsugu, Study of bone formation around dense hydroxyapatite implants using light microscopy, image processing and confocal laser scanning microscopy, BIOMATERIALS, 18, 4, 317-322, 1997.02, The bone reaction to hydroxyapatite (HA) implants inserted transcortically and extending into the medullary canal of rat tibiae was quantitatively assessed using light microscopy, confocal laser scanning microscopy and an image processing system. Sixty-five male rats (6 weeks old) were divided into two groups, 60 for histological observation and image analysis and five for time-labelling. In the histological observation, control sections of 168 days showed a few bone trabeculae in the fatty bone marrow, and Ti implants had become gradually encapsulated with a thick bone tissue layer; however, HA implants became almost completely encapsulated with a thin bone tissue layer during the 168 day experimental period. Histometrical analysis of the percent bone contact revealed that Ti implants showed a continuous increasing curve, and HA implants showed rapid increase in the initial healing period up to 14 days, with 96% bone contact reaching a plateau at 84 days after operation. There was a significant difference in the percent of bone contact between Ti and HA implants throughout the experimental period. Confocal laser scanning microscopic observations revealed the presence of calcein at the 14th day and only slight alizarin colour layer in the bone tissue at the 28th day, both indicating bone formation. These findings suggest that the activity of bone formation was higher at the 14th day than at the 28th day. Also, the percentage of bone contact of HA is superior to titanium throughout the experimental period, and the ascending patterns of both implants are quite different to each other. (C) 1997 Elsevier Science Limited. All rights reserved..
173. Histometric Study of Bone Formation around Titanium Implants Inserted into the Tibiae of Diabetes-Induced Rats : A Pilot Study
The influence of diabetes on the implant-bone interface of titanium (Ti) implants, inserted transcortically and extending into the medullary canal of rat tibiae, was examined, and the differences in bone reaction were quantitatively assessed using an image processing system. Thirty male Wister King A rats (aged 5 weeks) were used in this experiment, and they were divided into 2 groups, 15 for the control and 15 for the diabetes-induced (DI) group. They were sacrificed 7, 28 and 84 days after implant placement. Toluidine blue-stained undecalcified sections were prepared for histological observation and image analysis. The Ti implants in the bone marrow area had been almost encapsulated in a thick bone layer. The Ti implants in the DI group had been partially surrounded by a thin bone layer, but the thickness of the surrounding bone had decreased. Quantitative evaluation indicated that the control group showed an increase of the percent of bone contact, the thickness of surrounding bone and the area of surrounding bone throughout the experimental period, while the DI group showed a decrease of the thickness of surrounding bone and the area of surrounding bone except for the percent of bone contact..
174. 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)37:23.0.CO;2-D, 37, 2, 235-242, Vol.37,pp.235-242, 1997.01.
175. 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.
176. 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.
177. 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.
178. 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.
179. K Murai, F Takeshita, Y Ayukawa, T Kiyoshima, T Suetsugu, T Tanaka, Light and electron microscopic studies of bone-titanium interface in the tibiae of young and mature rats, JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 30, 4, 523-533, 1996.04, Bone-titanium contact was examined in young and mature rats on various days after insertion of pure titanium into the tibia. Under light microscopy, on the 14th day, lamellar mature bone was initially formed, and was seen to make direct contact with the titanium in both groups. In young rats on the 28th day, bone-titanium contact was greater than that in mature animals. On 1-mu m sections, an amorphous zone 0.5-1.0 mu m thick was found around the titanium, and a slender cell layer lay parallel to the implant, forming the superficial layer of the amorphous zone. Ultrastructurally, these slender cells were identified as osteoblastlike cells and made direct contact with the implant via a 20-50-nm thin amorphous zone. Below this cell layer, a collagen-containing, poorly mineralized zone was present and bordered by lamellar bone with a lamina limitans-like structure. However, this cell layer was absent in places, and therefore the thick amorphous zone without slender cell layer consisted ultrastructurally of a 20-50-nm thin amorphous zone and a poorly mineralized zone bordered by the lamellar bone. Sometimes this poorly mineralized zone was absent, and in such cases, the lamellar bone contacted the titanium by the thin amorphous zone formed on the lamina limitans-like structure. Thus, although bone was seen to make contact with the titanium implant, ultrastructurally a 20-50-nm thin amorphous zone, a slender cell layer, and/or a poorly mineralized zone were interposed between the bone and titanium. (C) 1996 John Wiley & Sons, Inc..
180. K Murai, F Takeshita, Y Ayukawa, T Kiyoshima, T Suetsugu, T Tanaka, Light and electron microscopic studies of bone-titanium interface in the tibiae of young and mature rats, JOURNAL OF BIOMEDICAL MATERIALS RESEARCH, 30, 4, 523-533, 1996.04, Bone-titanium contact was examined in young and mature rats on various days after insertion of pure titanium into the tibia. Under light microscopy, on the 14th day, lamellar mature bone was initially formed, and was seen to make direct contact with the titanium in both groups. In young rats on the 28th day, bone-titanium contact was greater than that in mature animals. On 1-mu m sections, an amorphous zone 0.5-1.0 mu m thick was found around the titanium, and a slender cell layer lay parallel to the implant, forming the superficial layer of the amorphous zone. Ultrastructurally, these slender cells were identified as osteoblastlike cells and made direct contact with the implant via a 20-50-nm thin amorphous zone. Below this cell layer, a collagen-containing, poorly mineralized zone was present and bordered by lamellar bone with a lamina limitans-like structure. However, this cell layer was absent in places, and therefore the thick amorphous zone without slender cell layer consisted ultrastructurally of a 20-50-nm thin amorphous zone and a poorly mineralized zone bordered by the lamellar bone. Sometimes this poorly mineralized zone was absent, and in such cases, the lamellar bone contacted the titanium by the thin amorphous zone formed on the lamina limitans-like structure. Thus, although bone was seen to make contact with the titanium implant, ultrastructurally a 20-50-nm thin amorphous zone, a slender cell layer, and/or a poorly mineralized zone were interposed between the bone and titanium. (C) 1996 John Wiley & Sons, Inc..
181. 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, JOURNAL OF PERIODONTOLOGY, 67, 2, 86-92, 1996.02, A CLINICAL STUDY WAS CONDUCTED of 59 patients treated with 78 hydroxyapatite (HA)-coated blade implants from August 1986. Five implants in 5 patients were broken at the neck portion, and one implant in one patient was removed from the jaw bone. The histological findings around a broken implant which was removed from the mandible are presented, These sections showed good adaptation of the bone to the implant without a fibrous layer. Histomorphometric evaluation of bone-to-implant contact showed 73.5%. The scanning electron microscopy image of the fractured surface revealed a fatigue fracture. The suspected cause of the fracture was stress concentration at the cervix portion, because of excessive mobility or deleterious change of abutment teeth. Consequently, the osseointegration/biointegration implants should not be connected with natural teeth..
182. 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, JOURNAL OF PERIODONTOLOGY, 67, 2, 86-92, 1996.02, A CLINICAL STUDY WAS CONDUCTED of 59 patients treated with 78 hydroxyapatite (HA)-coated blade implants from August 1986. Five implants in 5 patients were broken at the neck portion, and one implant in one patient was removed from the jaw bone. The histological findings around a broken implant which was removed from the mandible are presented, These sections showed good adaptation of the bone to the implant without a fibrous layer. Histomorphometric evaluation of bone-to-implant contact showed 73.5%. The scanning electron microscopy image of the fractured surface revealed a fatigue fracture. The suspected cause of the fracture was stress concentration at the cervix portion, because of excessive mobility or deleterious change of abutment teeth. Consequently, the osseointegration/biointegration implants should not be connected with natural teeth..
183. 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.
184. 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.
185. 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.
186. K. Murai, F. Takeshita, Y. Ayukawa, T. Kiyoshima, T. Suetsugu, T. Tanaka, Light and electron microscopic studies of bone-titanium interface in the tibiae of young and mature rats, J Biomed Mater Res, 10.1002/(SICI)1097-4636(199604)30:43.0.CO;2-I, 30, 4, 523-533, Vol.30,pp.523-533, 1996.01.