BONE REGENERATION AROUND DENTAL IMPLANTS WITH LOCAL ADMINISTRATION OF BISPHOSPHONATES

双膦酸盐（Bps）是治疗骨质疏松症的有效药物。Bps与骨中的磷酸钙化学结合并抑制破骨细胞的活化。此外，Bps还可通过直接促进破骨细胞凋亡来抑制骨吸收，FT-IR分析表明Bps与羟基磷灰石（HAp）发生化学结合。羟基磷灰石（HAp）作为载体的有效性进行了研究，以建立一种局部给药的双膦酸盐（Bps），目前已全身给药的方法。通过改变烧结温度，制备了粒径为300-500 μm的具有不同物理化学性质的HAp颗粒。为了确定HAp颗粒的物理化学性质，使用X射线衍射评估其结晶度，在扫描电子显微镜下检查表面形态，并评价比表面积和钙溶解。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。还评价了Bps-HAp复合物对破骨细胞存活率的影响。结果表明：1）HAp的溶解度与烧结温度有关; 2）通过调节HAp作为载体的烧结温度可以控制Bps的释放浓度; 3）Bps-HAp复合材料释放的Bps减少破骨细胞的数量。在此基础上，将二丁基偏磷酸铵盐加入到Ca-EDTA/胺复合物的乙醇溶液中，制备了分子前体溶液，构建了含DDS的钛-HAp支架。采用分子前驱体法在钛支架表面沉积含碳酸根的羟基磷灰石，这是一种新型的金属氧化物涂层技术。

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.