羟基磷灰石晶体结构的缺陷构建及铝、氟对骨代谢的作用与调控研究

Trace elements induce the defect structure of hydroxyapatite and influence the biochemical function in hard tissue of human body. In recent years, the incidence of abnormal bone metabolism caused by excessive accumulation of trace elements such as Aluminum-induced Bone Disease, Skeletal Fluorosis and Al-F Combined Toxicosis is increasing. To study the effects of Al and F elements in bone hydroxyapatite minerals, and to reveal the pathogenesis of the related diseases is an important issue in the field of clinical treatment and medical biomaterials. Based on the opposite effects of Al and F on crystallization behavior of hydroxyapatite, the project will take Al, F doped and Al-F co-doped hydroxyapatite as the research object; study and establish the relationship among crystal structure–properties–bone metabolism; regulates bone metabolism in a double-edged way by construction of crystal defects in hydroxyapatite. (1) Synthesis, structural characterization and physicochemical properties of Al, F doped and Al-F co-doped hydroxyapatite will be studied. (2) The crystal structure, electronic structure and stability of Al, F doped and Al-F co-doped hydroxyapatite will be investigated by the First Principle. (3) The effects of defect structure of Al, F doped and Al-F co-doped hydroxyapatite on human bone tissue metabolism will be studied, and the biological effects of Al, F in human bone tissue will be elucidated. Finally, the project will provide the scientific foundation for prevention and treatment of bone metabolic diseases, and design, preparation, structure and performance regulationof bone implant materials.

微量元素引起羟基磷灰石缺陷结构并影响在人体硬组织中的生化功能。由微量元素过量累积或缺失造成的铝骨病、氟骨症和铝氟联合中毒的发病率日益增高，研究铝、氟元素对骨羟基磷灰石矿物的作用，揭示发病机制问题，是临床治疗和医用材料领域的一个重要课题。基于铝、氟对羟基磷灰石结晶行为的相反作用，本项目拟以铝、氟和铝氟共掺杂羟基磷灰石为研究对象，建立铝氟掺杂羟基磷灰石的晶体结构—物化性质—骨代谢之间的构效关系，通过羟基磷灰石缺陷结构构建，实现对骨代谢的双向调控。（1）研究铝氟掺杂羟基磷灰石的制备、结构表征及其物化性质。（2）利用第一性原理研究铝氟掺杂羟基磷灰石晶体结构、电子结构和稳定性。（3）研究铝氟掺杂羟基磷灰石缺陷结构对人体骨组织代谢的作用，阐明铝氟元素在人体骨组织中的关联生物学效应。为骨代谢疾病预防和治疗以及植入体材料的设计、制备、结构和性能调控提供相关理论依据并奠定科学基础。

微量元素引起羟基磷灰石（HA）缺陷结构并影响在人体硬组织中的生化功能。研究微量元素对骨羟基磷灰石矿物的作用是临床治疗和医用材料领域的一个重要课题。本项目制备了铝、氟等微量元素掺杂羟基磷灰石粉体、陶瓷和等离子喷涂涂层，研究了其组分、晶体结构以及生物学效应，揭示了微量元素掺杂羟基磷灰石的晶体结构和性能之间的构效关系。（1）微量F掺杂HA（F0.02）的晶体结构中存在的缺陷数量明显高于HA及大量F掺杂HA样品。Ca缺陷的存在使F0.02晶体结构中形成生物反应活性中心，使之兼具优异的成骨活性和抗菌性。（2）Al掺杂在HA中引起配位缺陷，引起周围O原子的电荷转移和再分配，导致配位O原子的负电荷增加。这些O原子通过静电和氢键作用进一步成为溶菌酶分子的对接位点，进而赋予羟基磷灰石抗菌性。（3）铝掺杂导致羟基磷灰石晶格畸变，使羟基磷灰石更容易被降解，过量铝掺杂羟基磷灰石涂层植入体表现出新骨组织薄且存在大量骨吸收陷窝，微量铝掺杂羟基磷灰石涂层植入体可适度刺激破骨作用，与成骨作用保持平衡，从而促进骨形成。（4）通过在空气中简单的热处理策略，在HA中引入微量Mn3+和H空位（V'H）对，实现羟基磷灰石高抗菌活性和生物活性。（5）揭示了Sr掺杂对HA晶体结构的各向异性膨胀效应。c轴方向的相对膨胀率约为a轴方向的2.22倍。Sr优先取代Ca(1)位，SrO6构型中的Sr-O键长度比Ca(1)O6构型中的Sr-O键长度增加，由于该构型在不同方向上的投影长度不同，导致晶格各向异性膨胀。本项目研究揭示了微量元素在骨羟基磷灰石中的生物学效应，为羟基磷灰石生物材料的设计、制备、结构和性能调控提供相关理论依据并奠定科学基础。