近红外响应型microRNA纳米智能传递系统复合可注射功能化丝蛋白多肽水凝胶用于腔隙型骨缺损修复的研究

口腔颌面部不规则腔隙型骨缺损的微创治疗一直是临床上亟待解决的难题，可注射水凝胶材料为微创手术提供了新思路。本课题在前期研究的基础上，将功能化丝蛋白自组装多肽水凝胶与microRNA纳米运输系统相结合形成近红外响应型可注射复合水凝胶体系。首先将E7多肽引入到丝蛋白多肽（SF16）序列中，制备并检测自组装多肽水凝胶（E7/SF16）的材料学特性；而后构建以聚多巴胺（PDA）纳米颗粒为载体的近红外响应型miR-181a纳米运输系统，评价其对miR-181a的细胞内转运效率；最终将miR-181a纳米运输系统当作生物学信号负载于多肽水凝胶中（E7/SF16-PDA/miR-181a），验证其光热响应性及生物学活性，进一步通过兔上颌窦提升模型评估复合水凝胶的成骨效果。本研究所构建的可注射型复合水凝胶结合了外部刺激和内部响应的设计，有望成为治疗口腔颌面部不规则腔隙型骨缺损的新型骨再生修复材料。

Minimally invasive therapy of oral and maxillofacial irregular lacuna bone defect has always been a difficult problem remaining to be solved in clinic, for which injectable hydrogel can provide new thoughts. Based on the preliminary studies, this project will establish a near-infrared response injectable composite hydrogel system by combining the functionalized self-assembling silk fibroin peptide hydrogel with the microRNA nano-delivery system. Firstly, E7 peptide will be introduced into silk fibroin peptide (SF16), and the self-assembled peptide hydrogel（E7/SF16）will be prepared and tested; then, a near-infrared responsive miR-181a nano-delivery system based on PDA nanoparticles will be constructed, and its intracellular transport efficiency will be evaluated; finally, the miR-181a nano-delivery system is used as a biological signal to load in the peptide hydrogel system（E7/SF16-PDA/miR-181a）, verifing their photothermal response and biological activity, and the osteogenic effect of the composite hydrogel will be further evaluated by the rabbit maxillary sinus elevation model. The injectable composite hydrogel to be constructed in this study combines the design of both external stimulation and internal response，which is expected to provide new biomaterials for the treatment of irregular lacuna bone defect.