超顺磁性/荧光纳米HA晶体在内置磁场协同作用下成骨示踪研究

The quality of new bone reconstruction and osseointegration plays a pivotal role in long-term stability of dental implant, and further improvement of the speed and quality of new bone reconstruction is still the technical and clinical problems to be solved. In this project, hydroxyapatite (HA) nanocrystals doped with iron (Fe) ions inside and lanthanide (Ln) ions outside, or with Ln inside and Fe outside will be prepared by a two-step hydrothermal synthesis method, which have good osteogenic bioactivity, superparamagnetism as well as fluorescence tracking performance. The biological and osteogenic effects of the doping crystals (named HA:Fe/Ln) will be explored by the synergistic action of small magnet in titanium implant and HA:Fe/Ln crystals, and be traced by the fluorescence of the crystals. Under magnetic field, the orientation and surface environment of HA:Fe/Ln crystal will be changed，and the magnetic force will also exert stress stimulation on the new bone tissue, both will influence the osteogenesis behavior. The mechanism of material-cell and material-tissue interactions will be revealed by techniques such as molecular biology, histology, fluorescence imaging and micro-CT. It is expected to make breakthroughs in synergistic osteogenesis promotion of magnetic field-superparamagnetic HA crystals, material-cell/material-tissue interactions, and biomaterial tracking. It can also provide new material, method and support for future biomedical research and dental medicine.

口腔牙种植过程中，新骨重建和骨整合质量是种植体长期稳定存在的基础，进一步提高新骨重建速度和质量依然是有待解决的科技和临床难题。本项目用分步水热法制备内部含铁离子、外部含稀土离子的纳米羟基磷灰石晶体（HA:Fe/Ln），或采用先Ln后Fe的合成方法，使其同时具备成骨生物活性、超顺磁性和荧光示踪性能。通过在钛种植体内部安置小磁体并与HA:Fe/Ln晶体协同作用，来探索晶体的生物学效应和促进成骨作用，并通过该晶体的荧光特性示踪其成骨过程与效果。在磁场作用下，HA:Fe/Ln晶体的排列及表面环境将发生改变，所受磁作用力也会赋予重建新骨应力刺激，进而协同影响其成骨行为。借助分子生物学、组织学、荧光成像和显微CT重建等技术揭示材料-细胞和材料-组织相互作用机制。期待在磁场-超顺磁性HA晶体协同促进成骨、材料与细胞和组织相互作用、生物材料示踪研究等方面取得创新突破，为生物医学研究提供新材料和新方法，为口腔临床提供科学数据支撑。

口腔牙种植过程中，新骨重建和骨整合质量是种植体长期稳定存在的基础，进一步提高新骨重建速度和质量依然是有待解决的科技和临床难题。本研究设计和制备了镱、钬离子和铁离子分步掺杂的超顺磁性/上转换荧光HA纳米晶体（HYH-Fe），以及设计制备了可提供局部静磁场的内置可移除磁棒的钛种植体（mTi），考察拥有局部静磁场的mTi种植体与超顺磁HYH-Fe纳米材料的促成骨作用。研究表明，mTi种植体(静磁场)和超顺磁HA纳米材料的协同作用，可以有效提升细胞增殖和成骨基因表达，并显著促进种植体的早期成骨和骨整合。借助HYH-Fe材料的多模态成像能力可以长期示踪材料在新骨重建和修复过程中的分布和降解情况，为长期示踪植入材料并评价其修复效果提供了可行性。本项目研制的mTi新型种植体、超顺磁HYH-Fe纳米材料以及示踪技术，具有广阔的生物医学应用前景。