药物负载型氟化石墨烯增强透明质酸在关节滑液中的摩擦学性能研究

Lubrication deficiency induced abrasion of articular cartilage at joint surface and inflammation is one of the most important causes for osteoarthritis. Hyaluronic acid (HA) has been considered as the first choice material for joint lubrication due to its special viscoelasticity, rheology and biocompatibility. However, the disadvantages of insufficient compressive strength under low frequency and high load, poor wear resistance, and fast decomposition of HA in human body greatly limit its further application and development. Based on our previous work, this project will choose fluorinated graphene (FG) nanosheets to reinforce HA by taking advantage of its high mechanical strength, self-lubrication and good biocompatibility. By employing molecular control and surface modification techniques, FG and HA will be covalently linked to raise the friction-reduction and anti-wear as well as the anti-decomposition properties. Moreover, in order to lower the impact of inflammation induced free radicals for HA decomposition and extend the lubrication time, anti-inflammatory drugs will be loaded onto the surface of FG by using its high surface area and strong electronegativity of fluorine atoms. Then the tribological behaviors of FG reinforced HA in synovial fluid will be systematically studied, and the structure-function relationship between covalent function, drug loading, and tribological properties will be studied. Meanwhile, the principle of anti-wear and friction reducing performance and mechanism for lubrication improvement will be investigated and illuminated detailedly. The successful implementation of this project will provide theoretical reference and technical support for the study of tribological behavior and mechanism FG reinforced HA in synovial fluid.

润滑不充分引起的关节软骨磨损与炎症是导致关节炎产生的重要原因，透明质酸（HA）优异的粘弹性、流变性及生物相容性，使之成为关节润滑的首选材料。但HA在低频高载时抗压强度不足、耐磨性差、降解速度快等问题制约了其进一步应用。在前期研究基础上，本项目拟利用机械强度高、自润滑与生物相容性能好的氟化石墨烯（FG）纳米片来增强HA，借助分子调控与表面修饰技术，以共价键方式实现两者有效结合，进而提高HA抗磨减摩与抗酶解性能。利用FG高的比表面积与氟元素强的电负性，设计负载治疗关节炎的药物，降低炎症产生的自由基对HA的降解作用，进一步延长其润滑作用时间。在此基础上开展FG增强HA在关节滑液中的摩擦学性能研究，建立共价修饰方式、药物负载与摩擦学行为之间的构效关系，阐明其抗磨减摩性能提高的作用原理与润滑机制，为新型FG增强HA在关节滑液中的摩擦学行为与机制研究提供理论借鉴与技术支持。

关节软骨磨损与炎症是导致关节炎产生的重要原因，本项目针对关节润滑材料透明质酸（HA）在关节炎治疗过程中存在的抗压强度不足、耐磨性差、降解速度快等问题，采用机械强度高、自润滑与生物相容性能好的氟化石墨烯（FG）来增强HA，借助分子调控与表面修饰技术，以共价键方式实现了两者有效结合，显著提高了HA在仿生关节滑液中的抗磨减摩性能与使用寿命。利用FG高的比表面积与氟元素强的电负性，设计负载了治疗关节炎的药物，利用FG良好的光热转换性能，实现了药物的响应性释放，降低了炎症产生的自由基对HA的降解作用。在此基础上开展了FG增强HA在关节滑液中的摩擦学性能研究，建立了共价修饰方式、药物负载与摩擦学行为之间的构效关系，阐明了其抗磨减摩原理与润滑机制，为新型FG增强HA在关节滑液中的摩擦学行为与机制研究提供了理论借鉴与技术支持。主要研究成果如下：（1）建立了FG纳米片、FG量子点等纳米材料制备和元素含量调控方法，系统研究了材料制备、表面共价修饰、尺寸调控技术，从微观结构、化学组成、荧光、光热转换等方面研究了其理化性能。（2）系统研究了不同材料对消炎药物的可控负载、可视化监控与近红外光响应性释放等性能，评价了其细胞毒性，研究了其炎症治疗效果和对软骨细胞的保护性能。（3）系统研究了不同FG润滑材料在多种工况下的摩擦学行为，发展了具有长效润滑寿命与药物缓释性能的关节滑液添加剂，详细研究了摩擦前后表面微观结构与组成变化，揭示了其在关节润滑中的抗磨减摩机制。