石墨烯水凝胶负载EPCs来源外泌体调控PI3K-AKT通路修复颌骨缺损的研究

颌骨缺损重建是颌面外科领域亟待解决的问题，组织工程骨的应用是解决该问题的有效手段。前期课题组成功制备生物相容性优良的新型骨组织工程材料——自撑式石墨烯水凝胶（SGH），并首次揭示其良好的骨诱导性，但其成血管能力并不理想。缺乏充足的血供不仅影响种子细胞增殖分化，甚至会使组织工程骨失效。改善血管化实验中我们观察到内皮祖细胞外泌体能促进血管新生，故本项目拟将该外泌体与石墨烯水凝胶复合形成可促血管化的组织工程骨（SGH-exo），通过下列研究来探讨其血管化成骨能力及可能机制：1）构建上述组织工程骨，观察其体外接种间充质干细胞后的成骨成血管能力；2）研究SGH-exo负载和释放外泌体能力，采用RNA-Seq分析差异表达基因和富集通路，并验证其在成骨成血管过程中对PI3K-AKT通路的调控作用；3）将其应用于大鼠颌骨缺损修复，评估其体内血管化成骨能力；以期为组织工程骨应用面临的血管化问题提供改进方案。

Reconstruction of jaw defects is an urgent problem to be solved in the field of oral and maxillofacial surgery, and the application of tissue engineering bone is an effective means to solve this obstacle. In our previous study, we have successfully prepared novel biocompatible graphene tissue engineering scaffolds (Self-Supporting Graphene Hydrogel，SGH) ,and revealed its good osteoinductive properties, but it is not the ideal time in the body into blood vessels. The lack of adequate blood supply not only affects the proliferation and differentiation of seed cells, and even make the transplanted tissue engineering bone impossible to work effectively. We observed that exosome secretion of endothelial progenitor cells can promote angiogenesis in improvement of vascularization experiments, so this project was designed to explore the vascularized osteogenic potential of vascularized tissue engineering bone (SGH-exo) and its possible mechanism by creating exosomes and graphene hydrogel complex: 1) to construct the above-mentioned tissue-engineered bone and observe the osteogenic ability of mesenchymal stem cells in vitro; 2) to investigate the ability of SGH-exo to load and release exosomes, and verify its regulation of PI3K-AKT pathway in osteogenic process by using RNA-Seq analysis on differentially expressed genes and enrichment pathways; 3) to apply it to the repair of rat mandibular defect and evaluate its ability to vascularize osteogenesis in vivo that providing an improved solution to the problem of vascularization facing the application of tissue engineering bone.