表面接枝含RGD聚多肽的纳米羟基磷灰石制备及在骨组织工程中的应用

Hydroxyapatite/polymer nanocomposites have been widely used in bone tissue engineering, however, the phase compatibility between HA and polymer is poor, the HA particles could aggregate easily in the polymer matrix, in addition, the HA composites are lack of biofunctional groups that can tune cell interaction，all these reasons will limits its final applications in clinic. In this project, HA was firstly grafted by polypeptide with alkynyl groups via the ring openging polymerization of NCA monomers of different amino acids, and then RGD peptides, which can recognize integrin, are conjugated to the polypeptide chains via "Click" reaction, and thus endow the biorecognization funcation onto HA. the poylpeptide chanins may prevent the aggregation of HA nanoparticles and enhance the phase compatibility between HA and polymer matrix， on the other hand, RGD may improve the cell adhesion and proliferation ablity of HA. the affection of surface modification on the properties of HA were evaluated by cell experiments, and the properties of modified HA/PLGA scaffolds were evaluated both in vitro and in vivo. On the whole, Investigations in this project may be helpful to understand the relationship between the surface properties of HA and its biofunctions, meantime, it is expected to obtain bone tissue engineering scaffolds with excellent properties.

羟基磷灰石/聚合物纳米复合材料在骨组织工程领域得到广泛研究，但是，纳米羟基磷灰石（HA）与聚合物界面相容性差、纳米HA易聚集，复合材料缺乏调控调细胞相互作用的智能单元，这些缺点将限制其在临床的应用。本项目利用NCA开环聚合的方法，在纳米羟基磷灰石表面接枝含炔基的聚多肽，然后通过"Click"反应，将对整合素具有特异识别功能的RGD短肽键合在聚多肽侧基上，赋予纳米羟基磷灰石生物识别功能。一方面，聚多肽分子链的存在，可以阻碍纳米羟基磷灰石的聚集，增强其与聚合物的相容性；另一方面，RGD的存在可以增强纳米羟基磷灰石对细胞的粘附能力、促进细胞的增殖。利用细胞实验，评价表面改性对羟基磷灰石性能的影响规律；并从体外、体内等不同层次评价了改性纳米羟基磷灰石/PLGA组织工程支架的性能。本项目的研究有助于了解表面性质与纳米材料性能的关系，同时，有望开发出性能优良的骨组织工程支架材料。

羟基磷灰石/聚合物纳米复合材料在骨组织工程中具有很好的应用前景，但是纳米羟基磷灰石（HA）与聚合物界面相容性差、纳米HA易聚集，复合材料缺乏调控调细胞相互作用的智能单元。在国家基金的资助下，我们制备了表面接枝聚多肽的改性纳米羟基磷灰石，实现了HA在有机体系（如氯仿溶剂、聚乳酸基体）中的均匀分散。制备了改性纳米羟基磷灰石/聚乳酸多孔支架材料，并从体外评价了支架材料的生物相容性和生物活性；体内实验进行了大鼠颅骨和股骨的修复实验，8周后的骨修复实验结果表明表面接枝聚多肽的改性纳米羟基磷灰石/聚乳酸能够很好的促进骨组织再生。此外，通过电纺丝技术将表面接枝聚合物的羟基磷灰石、纳米氧化锌、富勒烯、聚合物胶束等纳米体系与PLLA、PLGA等高分子结合获得了复合纳米纤维，并研究了其作为组织工程支架和药物载体的应用前景，该方法能够同时将不同性质（如亲水性和疏水性）的药物负载在同一纤维体系，实现多级控释；采用贻贝仿生方法，制备了具有抗菌功能的含银组织工程支架和表面接枝RGD的组织工程支架，体外抗菌实验及细胞毒性实验表明所制备的组织工程支架具有良好的生物相容性及抗菌性能。