神经血管化仿生骨膜原位诱导神经再生及神经-血管网络重建促进骨再生研究

难治性骨缺损一直是骨科巨大挑战，植骨材料单独使用疗效不佳。国内外和本团队近年发现，天然骨膜富含的神经及神经血管网络，为启动和诱导骨再生提供了重要的微环境。而目前骨再生的研究多是从成骨/成血管角度，对神经调控成骨的重要性才初步认识，亦未构建出能原位诱导神经再生、重建神经血管网络的仿生骨膜。.本课题从神经、神经血管网络的角度研究成骨。在长期从事组织诱导材料原位诱导骨和神经再生的基础上，以源于天然的具有良好神经/血管再生活性的神经脱细胞基质和小肠粘膜下层脱细胞基质为基材，同轴电纺获得定向微纳纤维结构和更好力学强度，负载NGF、VEGF和特异性核酸适配体，获得能诱导内源性背根神经节神经纤维和血管内皮祖细胞靶向募集、定向迁移、定向分化的神经血管化仿生骨膜。.通过对神经再生、神经血管网络重建、神经-血管-骨交互对话机制的探讨，为原位诱导骨再生提供理想微环境，亦将丰富近年才起步的神经调控成骨的理论体系。

Refractory bone defects have always been a great challenge for orthopedics, and independent bone grafts can hardly achieve satisfactory effects to cure them. Domestic and international and our team have recently reported that the nerve and neurovascular network rich in natural periosteum can provide a crucial microenvironment for initiating and inducing bone regeneration. However, major of current studies on bone defect repair remain focused on osteogenesis/angiogenesis, but the importance of nerve on regulating osteogenesis is just preliminarily recognized, along with no constructed biomimetic periosteum able to induce in situ nerve regeneration and neuron-vascular network reconstruction.. Based on our long term researches on tissue inducing materials for in situ bone and nerve regeneration, this project focuses on investigating bone regeneration from the perspective of nerve and neuron-vascular networks. To develop an innovative neurovascularized biomimetic periosteum that can induce endogenous dorsal root ganglion fibers/endothelial progenitor cells targeted recruitment, directional migration and differentiation, natural decellularized nerve matrix with good neurogenesis activity and small intestinal submucosa with good angiogenesis activity are selected as substrates, which are then constructed by coaxial electrospinning to achieve an oriented micro-/nano- fiber structure with stronger mechanical strength, along with incorporation of NGF, VEGF and specific aptamers respectively.. By investigating the mechanism of nerve regeneration, neuron-vascular network reconstruction and cross-talks among nerve-vascular-bone, an ideal microenvironment is explored for inducing in situ bone regeneration, which will yet enrich the recently started theoretical system of neuroregulation on osteogenesis.