自组装短肽-纳米羟基磷灰石复合生物活性材料的制备及骨修复机制研究

Bone defects, especially weight-bearing bone defects and large bone defects, have become ubiquitous and are hard to treat in clinical application. Although there are many material scaffolds that are being studied or applied in clinical treatment, it is difficult to coordinate their features of good bioactivity and mechanical stress for bone healing. Under certain conditions, self-assembly peptides can spontaneously assemble into three-dimensional scaffolds mimicing extracellular matrices, and many studies have revealed their promotion to cell function and tissue repair, especially when using functional motifs-modified peptides. It is believed that nano-hydroxyapatite can be combined with peptide-formed matrices to significantly increase the mechanical stress of hybrid composite. This project is intended to integrate the properties of functional motif, self-assembly peptide and nano-hydroxyapatite, which can provide some theoretical support for our hypothesis: hybrid composite consisting of self-assembly peptide and nano-hydroxyapatite can significantly induce bone repair. In order to identify it, we will fabricate this hybrid composite in the best ratio of two components through physical and chemical analysis, mechanics of materials, control release and degradation efficiency. Its impact on bone repair and bone healing can be explored by cell culture, neo-bone formation under the skin and within the muscle. The related mechanisms are possibly associated with ERK and MAPK-mediated regulation, and they are the most important and difficult parts of this project. This project has significant influence on the fabrication of material scaffolds for bone repair and the research of related mechanisms.

骨缺损，尤其是负重部位骨缺损和大段骨缺损临床常见且处理棘手。尽管临床或在研的骨修复材料众多，但其生物活性和力学性能很难兼顾。自组装短肽在适当的条件下可形成类细胞外基质的三维支架，实验证实其对细胞功能及组织修复有重要作用。且功能基序修饰后的短肽可提高支架的生物活性。肽支架引进纳米羟基磷灰石后可增强材料的力学性能。本研究旨在整合功能基序、短肽和纳米羟基磷灰石的生物活性和力学性能为一体。因此，我们提出"自组装短肽-纳米羟基磷灰石复合生物活性材料对骨修复具有良好的促进作用"的假说。为证实这一假说，课题组通过理化性质分析、材料力学、控制释放和降解效率来探索并研发出最佳材料组分配比的骨修复材料，并从细胞培养、皮下组织袋和肌袋内骨形成层面来探索该复合材料对骨形成与骨修复的作用，揭示其骨修复机制，ERK介导的信号通路和MAPK信号通路是我们研究的重点。本课题对骨修复材料的制备和骨修复机制的研究有重要影响。

随着建筑交通事故频发、老年化加剧，骨缺损患者数量巨大，尤其部分患者遭受骨延迟愈合、骨不连等。很多骨缺损患者都需要植骨，由于自体骨取骨量有限及相关并发症，研究兼有优良成骨能力和足够力学强度的复合材料迫在眉睫。本课题组采用多孔纳米羟基磷灰石/聚酰胺66复合自组装肽制备复合生物骨修复材料，生物环境下理化性质稳定，可作为生长因子缓释的满意载体；对细胞增殖和成骨分化有重要促进作用，且其成骨作用与P38 MAPK信号通路有关；进一步通过动物骨缺损模型证实复合材料对骨修复的显著应用价值。