DEVELOPMENT OF DENTAL IMPLANTS FOR IMPROVING OSTEOPOROSIS -ENHANCEMENT OF OSTEOGENISIS BY SURFACE MODIFICATION-

开发用于改善骨质疏松症的牙种植体 -通过表面修饰增强成骨作用 -

• 批准号: 10671845
• 负责人: YOSHINARI Masao
• 金额: $ 1.22万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671845/
• 关键词: Dental implant; Osteoporosis; Calcium phosphate; Titanium; Thin film; Bisphosphonate; Ion beam mixing; Rapid heating

Thin calcium-phosphate coatings prduced by the ion beam mixing method instead of the plasma spraying method were amorphous, resulting in films that easily dissolved in simulated body fluid. These costings crystallized with conventional heat treatment in an electric furnace but tended to crack easily. Therefore, this study aimed to find a suitable heat treatment that controls the solubility of Ca-P coations without weakening adhesion to titanium substrate. Thin coatings (approximately 1 μm) were coated onto the titanium substrates, followed by heat-treatment with conventional furnace heating and rapid heating of infrared radiation and laser radiation. These data indicate that rapid, homogeneous, and comparatively low temperature heating such as defocused infrared radiation around 600℃ controls Ca-P solubility and ensures the adherence of the coatings.Bisphosphonates are a new class of drugs that have developed for use in treating several diseases related to bones, teeth, and calcium met … More abolism. These compounds are potent inhibitors of bone resorption, and inhibit soft tissue calcification in vivo. The efficiency of surface modifications on the immobilization of bisphoshonates on titanium was investigated with Ca-ion implantation, thin hydroxyapatite coatings and β-tricalcium phosphate coatings. The ALP activity of osteoblastic cells and the inhibitory effects on the initial adherence of P. gingivalis were also evaluated using bisphosphonate-immobilized titanium. X-ray photoeletron spectroscopy analysis suggested that titianium surfaces modified with Ca-ion implantation and thin hydroxyapatite coatings caused the immobilization of bisphosphonate on titanium plates.The ALP activity of osteoblastic cells cultured on plates immobilized with bisphosphonate was almost same as that of cells cultured on titanium plates, indicating that the bisphosphonate-immobilization showed no toxic effect on osteoblastic cels, and that it provides a favorable micro-enviroment with osteogenetic ability. Data of the adherence of oral bacteria showed that a bisphosphonate-immobilized titanium surface inhibited the initial adherence of P. gingivalis. These results indicate that the immobilization of bisphosphonates on titanium modified with Ca-ion implantation and thin hydroxyapatite coatings are useful for dental implants.Activity of osteoblastic cells, which were isolated from calvariae of rats, decreased on the Ca-P surface with high dissolution rate in vitro. The surfaces of Cp-titanium of 3.0mm in diameter were modified with (1) titanium-blast + acid etching, Ca-implantation, thin HA coating of 0.5μm in thickness using an ion beam dynamic mixing (IBDM) method, and hisphosphonate-treating at a bone tissue/implant interface, (2) making a hole with pore size of 100 μm at a soft tissue/implant surface with 0.5mm and 1.5mm wide,and (3) F-implantation and alumina coating of 1μm in thickness at surfaces exposed to oral cavity. These implants were implanted into Beagle dogs, and then carried out with histopathological examination at 4 an 8 weeks after implantation. Even though a detailed analysis was not yet done, ossointegration was observed on comparative early stage after implantation. Less

用离子束混合法而不是等离子喷涂法制备的钙磷薄膜为非晶态，易溶于模拟体液。这些成本在电炉中用传统的热处理结晶，但容易破裂。因此，本研究旨在寻找一种合适的热处理工艺，在不削弱与钛基材的附着力的情况下控制钙磷涂层的溶解度。在钛衬底上涂覆薄涂层(约1μm)，然后用传统的炉子加热和红外线和激光辐射的快速加热进行热处理。这些数据表明，快速、均匀和相对低温的加热，如600℃左右的散焦红外辐射，控制了Ca-P的溶解度，并确保了涂层的附着力。双膦酸盐是一种新型药物，已开发用于治疗几种与骨骼、牙齿和钙相关的疾病Met…更多新陈代谢。这些化合物是有效的骨吸收抑制剂，并在体内抑制软组织钙化。用钙离子注入、薄层羟基磷灰石涂层和β-磷酸三钙涂层研究了表面改性对钛表面固定双磷酸盐的效果。用双膦酸钛固定成骨细胞，观察成骨细胞碱性磷酸酶的活性及对牙龈假单胞菌初始黏附的抑制作用。X-射线光电子能谱分析表明，钛表面经钙离子注入和薄层羟基磷灰石涂层处理后，双膦酸盐在钛板上的固定化效果良好，其成骨细胞的碱性磷酸酶活性与钛板上培养的细胞几乎相同，说明双膦酸盐固定化对成骨细胞无毒性作用，具有良好的成骨微环境。口腔细菌黏附数据显示，双膦酸盐固定的钛表面抑制了牙龈假单胞菌的初始黏附。这些结果表明，钙离子注入改性钛表面和薄层羟基磷灰石涂层固定化双膦酸类化合物可用于牙种植体。体外分离的大鼠颅骨成骨细胞在钙磷表面活性降低，溶出率高。对直径3.0 mm的CP钛进行表面改性处理：(1)喷钛+酸蚀、钙离子注入、离子束动态混合法制备0.5μm厚的HA涂层、在骨组织/种植体界面处进行组磷酸盐处理；(2)在0.5 mm和1.5 mm宽的软组织/种植体表面打孔；(3)口腔暴露表面F-离子注入和氧化铝涂层1μm厚。将这些种植体植入Beagle犬体内，分别于植入后4周和8周进行组织病理学检查。尽管还没有进行详细的分析，但在种植后的相对早期就观察到了骨整合。较少

项目成果

宮山直也,吉成正雄 ほか: "ドライプロセスによるインプラント用チタンの表面改質-表面の特性評価-"歯科材料・器材. 18・2. 109-121 (1999)

Naoya Miyayama、Masao Yoshinari 等：“干法种植体钛的表面改性 - 表面特性的评估 -”牙科材料和设备 18・2（1999）。

Ayukawa,Y., et al.: "An immunocytochemical microscopic locarization of noncollagenous bone protein (osteocalcin and osteopontin) at the bone-titanium interface"J Biomed Mater Res. 41・2. 111-119 (1998)

Ayukawa，Y.，等人：“骨-钛界面处非胶原骨蛋白（骨钙蛋白和骨桥蛋白）的免疫细胞化学显微定位”J Biomed Mater Res 41·2（1998）。

吉成正雄 ほか: "ハイドロキシアパタイトコーティング・インプラント材の溶解特性"生体材料. 16・3. 133-144 (1998)

Masao Yoshinari 等：“羟基磷灰石涂层植入材料的溶解特性”Biomaterials 16・3（1998）。

Ayukawa, Y., et al.: "An immunocytochemical microscopic locarization of noncollagenous bone protein(osteocalcin and osteopontin)at the bone-titanium interface"J Biomed Mater Res. 41・2. 111-119 (1998)

Ayukawa，Y.，等人：“骨-钛界面处非胶原骨蛋白（骨钙蛋白和骨桥蛋白）的免疫细胞化学显微定位”J Biomed Mater Res 41·2（1998）。

Ikeda,H., Yamaza,T., Yoshinari,M., Ohsaki,Y., Ayukawa,Y., Kido,M.A., INOUE,T., Sshimono,M., Koyano,K., Tanaka,T.,: "Ultrastructural and immunoelectron microscopic studies of the peri-implant epithelium-implant (Ti-6Al-4V) interface of rat maxilla"Journal

池田，H.，山座，T.，吉成，M.，大崎，Y.，鲇川，Y.，木户，M.A.，井上，T.，志物野，M.，小矢野，K.，田中，T.，：