介孔羟基磷灰石微球的设计合成及其负载药物用于骨髓炎性治疗研究

Treatment of osteomyelitis and repair of bone are the research hotspots and problems for clinical orthopedic. The mesoporous materials possess unique surface/interface effect and cooperative properties which are different from those of individual nanocrystals and bulk counterparts. Hydroxyapatite (HA), as one of the artificial bone materials, exhibits excellent biocompatibility and osteoinduction. In addition, the introduction of meso-structure can provide abundant attachment sites for bioactive molecules or proteins/cells and others, which is expected to solve the application bottlenecks facing traditional drug-loading materials, including weak biocompatibility, low loading efficiency and high cost, etc. In this project, novel and efficient method combining interface assembly and soft-templating synthesis techniques will be explored to synthesize mesoporous HA microspheres. Amphiphilic block copolymers with unique properties will be designed and used as soft templates to co-assembly of functionalized-HA nanoparticles and synthesize mesoporous microspheres with good biocompatibility and high porosity. These novel microspheres will be applied in efficiently loading and controllable in situ release of antibiotics for inhibition of osteomyelitis. The interaction between HA nanoparticles and templates can be tunable through engineering HA nanoparticles with specific characteristics (surface properties, size, morphology, etc). These HA-based mesoporous microsphere materials are expected to open up great possibility for the HA materials to be used in clinical trials of osteomyelitis and bone tissue regeneration.

骨髓炎治疗及骨修复是当前临床骨科的研究热点和难题。介孔结构材料拥有不同于纳米颗粒和块体材料的独特表/界面效应和协同性能。羟基磷灰石（HA）作为人工骨骼材料之一，具有较高的生物相容性和骨诱导性，而介孔结构的引入可为活性因子或蛋白/细胞等提供丰富的附着点，有望解决传统载药材料的生物相容性差、负载效率低及成本高的瓶颈。本课题拟结合溶剂挥发诱导聚集共组装、软模板合成等技术，采用两亲性嵌段共聚物为模板，通过模板剂与表面修饰的HA纳米颗粒协同组装，合成生物相容性的介孔HA微球，并将其用于骨髓炎治疗药物—抗生素的负载-原位释放。通过调控、设计和构筑具有可调表面性质的HA纳米颗粒，诱导HA纳米颗粒与模板剂相互作用。本项目有望实现HA介孔微球的高效可控合成及其用于抗生素负载、药物的原位释放以及骨诱导生长应用，为骨髓炎及骨组织再生临床治疗提供新的药物载体和治疗依据。

活性生物材料是一类极具发展前景的功能材料，在活性生物材料中引入介孔结构将赋予其独特的理化性质，包括光响应性、磁响应性等。通过磁性微球表面包覆技术实现不同功能组分材料的集成，从而为骨髓炎疾病治疗和临床药物递送提供重要参考。本项目围绕骨髓炎治疗的活性药物负载及均匀可控的介孔材料精准制备展开了系列深入的研究，系统总结和概述了介孔生物活性材料在骨髓炎治疗、药物负载领域的应用进展，制备出具有高活性和实用价值的介孔生物活性材料。发展了界面诱导共组装、“bottom-up自下而上”共组装等超分子化学和界面化学合成策略，成功创制了一批具有高比表面积、开放连通的介孔孔道和可调控的磁响应/药物负载量的功能介孔材料，实现了材料理化性质的调控、微纳结构的设计及其在骨髓炎治疗领域的性能优化，并将其应用于生物医疗、药物递送及骨科疾病治疗等领域。相关研究成果发表于Adv. Mater.、Angew. Chem. Int. Ed.等材料化学顶级期刊，共计40篇SCI论文，同时授权中国发明专利4项。该项目研究成果推动了介孔生物活性材料及骨科的发展，为新型介孔生物医用材料的开发奠定了理论基础。