氟化生物源性羟基磷灰石溶解平衡与促进成骨的机制研究

生物源性羟基磷灰石是口腔临床应用最广泛的骨组织替代材料，但由于其缺乏骨诱导性，学者们试图对其改性以更好地满足骨缺损修复的临床需求。离子掺杂是磷灰石材料改性研究的热点，氟是参与骨改建中促进成骨的微量元素，因此氟离子植入被认为可能提高磷灰石材料的成骨性能。我们在过往的研究中以高温化合置换法对生物源性羟基磷灰石(猪骨)进行氟离子植入，制备完成氟化生物源性羟基磷灰石（FBHA），后续研究发现FBHA具有良好生物相容性且能促进细胞成骨分化，但其促进成骨的机制尚不明确。本项目拟在前期研究基础上，运用固体滴定和激光散射监测技术测定FBHA的等温溶解线并监测溶解平衡过程中离子动态变化；评估材料表面细胞行为和动物体内成骨性能；研究FBHA溶解平衡中氟离子影响细胞微环境并启动促进细胞成骨分化的相关信号通路机制。本课题是基于前期研究基础的深入性机制探讨，将加深对磷灰石无机材料促进成骨作用机制的理解。

Bio-derived hydroxyapatite is the most widely used bone substitute clinically in dentistry. However, due to the lack of osteoinductivity, there is still neccessity to further improve its osteogenesis capability to meet the clinical needs of reconstruction of bone defects. Ions incorporation is one of the popular methods for apatite modification. Fluorine is the trace element involved in bone remodeling in promoting osteogenesis. And therefore, fluoride ion incorporation to hydroxyapatite has been suggested to adjust the physicochemical properties of bone substitute material and promote osteogenesis. In our previous study, the high temperature chemical substitution reaction was explored to incorporate fluoride ions into bio-derived hydroxyapatite(porcine bone), and the fluorinated bio-derived hydroxyapatite(FBHA) was successfully prepared. In the follow-up study, FBHA has been confirmed to show good biocompatibility and promote osteogenic differentiation of osteoblast. However, the mechanism how FBHA promoted osteogenesis was still not understood. Based on preliminary studies, the solubility isotherm of FBHA would be determined with our innovative method, solid titration and laser-scattering end-point detection approach. The dynamic changes of ions would be analyzed with ion chromatography. The osteogenesis capability of FBHA would be evaluated both by cell culture in vitro and by animal studies in vivo. And the mechanism how dissolved fluoride ions from FBHA affect cellular microenvironment and further initiate cell signaling pathways to promote osteogenic differentiation would be investigated. This study aims to further discuss the mechanism how the equilibruim of FBHA affect promotion of osteogenesis, which could help to better understand the mechanism how inorganic materials promoted osteogenesis.