BONE REGENERATION AROUND DENTAL IMPLANTS WITH LOCAL ADMINISTRATION OF BISPHOSPHONATES

局部使用双膦酸盐促进牙种植体周围的骨再生

• 批准号: 15592065
• 负责人: YOSHINARI Masao
• 金额: $ 2.05万
• 依托单位: TOKYO DENTAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15592065/
• 关键词: Dental implant; Bisphosphonate; Bone regeneration; Hydroxyapatite; Drug delivery system; Sintering temperature; Local administration; Crystallinity

Bisphosphonates (Bps) have been used as an effective drug for patients suffer from osteoporosis. The Bps chemically binds to the calcium phosphate in the bone and suppresses the activation of osteoclasts. In addition, Bps is known to inhibit bone resorption by directly facilitating osteoclast apoptosis.It was revealed that the Bps chemically binds to the hydroxyapatite (HAp) by FT-IR analysis. The efficacy of hydroxyapatite (HAp) as a carrier was investigated in order to establish a method of local administration of bisphosphonates (Bps), which has currently been administered systemically. HAp granules 300-500 μm in size were prepared with different physicochemical features by altering the sintering temperature. To ascertain the physicochemical properties of the HAp granules, their crystallinity was assessed using X-ray diffraction, the surface morphology was examined under scanning electron microscopy, and the specific surface area and calcium dissolution were evaluated. Different Bps-HAp composites were subsequently prepared and the concentration of Bps released from these composites was measured. The influence of Bps-HAp composites on the rate of osteoclast survival was also evaluated. The results revealed that 1) HAp solubility depends on the sintering temperature ; 2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier ; and 3) Bps released from Bps-HAp composites reduced the number of osteoclasts. These findings indicated that Bps-HAp composites could be locally administered as a drug delivery system to areas with bone resorption.Furthermore, the molecular precursor solution was prepared by the addition of dibutylammonium metaphosphate salt into the ethanol solution of Ca-EDTA/amine complex to establish the titanium-HAp scaffold with DDS. Carbonate-containing hydroxyapatite was deposited onto titanium scaffold using molecular precursor method, which was novel technique for coating metal oxide film.

双膦酸盐（Bps）已被用作治疗骨质疏松症患者的有效药物。 Bps 与骨中的磷酸钙发生化学结合，抑制破骨细胞的活化。此外，已知 Bps 可通过直接促进破骨细胞凋亡来抑制骨吸收。通过 FT-IR 分析表明，Bps 与羟基磷灰石 (HAp) 发生化学结合。研究羟基磷灰石（HAp）作为载体的功效，以建立目前已全身给药的双膦酸盐（Bps）的局部给药方法。通过改变烧结温度，制备出具有不同理化特性的300-500 μm尺寸的HAp颗粒。为了确定 HAp 颗粒的物理化学性质，使用 X 射线衍射评估了它们的结晶度，在扫描电子显微镜下检查了表面形态，并评估了比表面积和钙溶解度。随后制备了不同的 Bps-HAp 复合材料，并测量了从这些复合材料中释放的 Bps 浓度。还评估了 Bps-HAp 复合材料对破骨细胞存活率的影响。结果表明：1）HAp溶解度取决于烧结温度； 2）通过调节HAp作为载体的烧结温度可以控制释放的Bps浓度； 3) Bps-HAp 复合材料释放的 Bps 减少了破骨细胞的数量。这些结果表明，Bps-HAp复合材料可以作为药物递送系统局部给药至骨吸收区域。此外，通过将偏磷酸二丁基铵盐添加到Ca-EDTA/胺复合物的乙醇溶液中来制备分子前体溶液，以用DDS建立钛-HAp支架。采用分子前驱体法将含碳酸盐的羟基磷灰石沉积在钛支架上，这是一种涂覆金属氧化物薄膜的新技术。

项目成果

Molecular precursor method for thin calcium phosphate coating on titanium

钛表面磷酸钙薄膜的分子前体法

• 发表时间: 2005
• 期刊: Thin Solid Films 484,1-2
• 作者: Takahashi K;Hayakawa T;Yoshinari M;Hara H;Mochizuki C;Sato M;Nemoto K
• 通讯作者: Nemoto K

Matsuzaka K, Yoshinari M, Shimono M, Inoue T: "Effects of multi-grooved surfaces on osteoblast-like cells in vitro : Scanning electron microscopic observation and mRNA expression of ostopontin and osteocalcin"J Biomed Mater Res. 68A. 227-234 (2004)

Matsuzaka K，Yoshinari M，Shimono M，Inoue T：“多凹槽表面对体外成骨细胞样细胞的影响：扫描电子显微镜观察和骨桥蛋白和骨钙素的 mRNA 表达”J Biomed Mater Res。

Effects of multi-grooved surfaces on osteoblast-like cells in vitro : Scanning electron microscopic observation and mRNA expression of ostopontin an osteocalcin

多孔表面对体外成骨样细胞的影响：扫描电镜观察和骨桥蛋白和骨钙素的mRNA表达

• 发表时间: 2004
• 期刊: J Biomed Mater Res 68A
• 作者: Matsuzaka K;Yoshinari M;Shimono M;Inoue T.
• 通讯作者: Inoue T.

平成15年度産業化を目指す健康医療メカトロニクスの新技術シーズと社会ニーズに関する調査研究報告

2003年面向产业化的健康医疗机电一体化新技术种子及社会需求研究报告

• 发表时间: 2004
• 作者: Seshima H;Yoshinari M;Takemoto S;Hattori M;Kawada E;Inoue T;Oda Y;吉成正雄(分担執筆);吉成正雄(分担執筆);山根隆志;吉成正雄(分担執筆)
• 通讯作者: 吉成正雄(分担執筆)

Effects of multigrooved surfaces on fibroblast behavior.

• DOI: 10.1002/jbm.a.10521
• 发表时间: 2003-06
• 期刊: Journal of biomedical materials research. Part A
• 作者: M. Yoshinari;K. Matsuzaka;T. Inoue;Y. Oda;M. Shimono