针对现有口腔局部用药存在患区停留时间短、浓度低、释药速度及给药时机难以控制等缺陷，本研究在引入具有良好骨诱导活性的NaCas-CaCO3微球的基础上，构建磁性CaCO3/Fe3O4纳米复合颗粒，利用环糊精的拓扑结构形成包结络合物，搭载米诺环素等模型药物，采用层层自组装技术被覆I型胶原/硫酸软骨素多层涂层，设计一种新型的具有磁靶向性、长效控缓释、酶识别响应的骨诱导性药物微胶囊。利用磁性种植基台引导药物在穿龈区浓集滞留，并由炎症相关因子组织蛋白酶-K和MMP-8反馈调控其释放水平；用人间充质干细胞体外研究载药系统的生物相容性、抑菌效应、磁靶向性能和成骨相关基因（CBFA1、 COLI、 ALP）表达水平变化，建立比格犬种植体周围炎模型评价体内药物代谢行为、抑菌效果和骨再生性。本课题构建的磁靶向智能控缓释系统兼具磁场和体内生物酶的双向调控性能，可望为种植体周围炎等多种疾病提供新型的载药模板。

Based on the fact of short duration, low concentration, and inaccurate administration during topical medication in oral cavity, we prepare the magnetic CaCO3/Fe3O4 hybrid nanoparticles with osteoinductive NaCas-CaCO3 microspheres and cyclodextrin. After incorporating the minocycline with these magnetic carriers with layer-by-layer self-assembly, the particles are functionalized with multi-coating Collagen Type I and Chondroitin Sulfate. This novel microcapsuled drug is characterized with magnetism, sustained and controlled release, enzyme-response, and osteoinduction. The drugs retardation at the transmucosal area is created by the magnetic abutment, and is regulated by the feedback of inflammation-related factors, Cathepsin-K and MMP-8. To analyze the biocompatibility, antibacterial effect, magnet-targeted ability, and expression of osteogenesis-related genes (CBFA1, COLI, and ALP) in vitro, we culture human mesenchymal stem cells with these microcapsuled drugs; to test the metabolism, antibacterial efficacy and bone regeneration ability in vivo, we establish a ligature-induced peri-implantitis model using magnetic abutments in beagle dogs. The current project will develop a smart magnetic controlled released drug delivery system that can be bidirectionally regulated by magnetic field and enzyme, which is promising in acting as a novel drug-loaded module in peri-implantitis and other diseases.