BONE REGENERATION AROUND DENTAL IMPLANTS WITH LOCAL ADMINISTRATION OF BISPHOSPHONATES

双膦酸盐(BPS)已成为治疗骨质疏松症的有效药物。磷酸二苯酯与骨骼中的磷酸钙化学结合，抑制破骨细胞的激活。此外，BP通过直接促进破骨细胞凋亡来抑制骨吸收。FT-IR分析表明，BP与羟基磷灰石(HAP)发生化学结合。为建立目前全身给药的局部给药方法，研究了羟基磷灰石(HAP)作为载体的有效性。通过改变烧结温度，制备了粒度为300~500μm、具有不同物化性质的羟基磷灰石颗粒。为了确定HAP颗粒的物理化学性质，用X射线衍射仪测定了其结晶度，用扫描电子显微镜观察了其表面形貌，并测定了其比表面积和钙的溶解情况。随后制备了不同的BPS-HAP复合材料，并测量了这些复合材料中BPS的释放浓度。此外，还观察了BPS-HAP复合材料对破骨细胞存活率的影响。结果表明：1)羟基磷灰石的溶解度依赖于烧结温度；2)以羟基磷灰石为载体的羟基磷灰石的释放浓度可以通过调节烧结温度来控制；3)羟基磷灰石-羟基磷灰石复合材料中释放的羟基磷灰石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释放系统局部应用于骨吸收区域。此外，通过在Ca-EDTA/胺络合物的乙醇溶液中添加二丁基偏磷酸铵盐制备分子前驱体溶液，建立具有DDS的钛-HAP支架。采用分子前驱体法在钛支架上沉积含碳酸盐的羟基磷灰石，这是一种制备金属氧化物薄膜的新技术。

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.