microRNA-222在骨组织工程中促神经化的研究及机制探讨

在大块骨的组织再生中，缺乏有效的血管神经网络是影响新生骨组织中心部位营养代谢和骨再生质量的重要原因。神经在骨形成过程中起到控制血流、调节代谢以及分泌神经营养因子等作用，对于新骨形成至关重要。本课题组前期研究显示miR-222具有促进人骨髓间充质干细胞的神经向分化潜能。据此，本研究将进一步探讨miR-222在分子水平对骨髓间充质干细胞的神经化促进作用，并通过深入研究 miR-222经Notch1和Wnt等通路的作用靶点，研究促神经化分子机制及神经化在骨再生中的作用。利用长期缓释miRNA的温敏纳米凝胶，本研究将miR-222缓释应用于动物骨缺损模型，观察骨缺损区域的成神经、成血管和成骨状况，进一步揭示促神经化对血管新生和骨再生的调控作用，进而获得骨组织工程中接近仿生效果的血管神经化新生骨。骨组织工程中促神经化的研究有望优化大块骨缺损的修复，也有助于应用到骨感知、应力反馈调节等多个研究领域。

During a large bone graft tissue regeneration process, the lack of efficient neuralized vascular network in the center bone area hinders the nutrient metabolism, thus jeopardizing the outcome of newly generated bone quality. Nerve tissue plays a vital role in the formation of bone via controlling the blood flow, regulating the bone metabolism as well as secreting of neurotrophic factors and so forth.Our previously study firstly discovered that miR-222 has the potential to enable hBMSCs to differentiate into neuro-like cells . In the subsequent study, we will further explore the neuro-differentiating effect of miR-222 on human bone marrow mesenchymal stem cells at the molecular level and the molecular mechanism by finding out the target gene of Notch 1and Wnt pathways so as to clarify the positive role of neuralization in bone regengeration. A thermosensitive nanoparticle hydorgel gene delivery system loaded with miR-222 will be applied in animal mandibular defects model in vivo.The nerve growth ,neovascularization and osteogensis will be analyzed and also the regulatory role of nerve in new bone formation would be revealed in this study in oder to acquire better innervated and more vascularized bionic functioning bone tissue. This study of neuralization in bone tissue engineering will make it possible for the repair of large bone defects, and it will also provide thoughts for various research fields such as osseoperception and feedback regulation of stress.