大段骨缺损的修复是骨科面临的巨大挑战之一。组织工程技术为骨缺损治疗带来了希望，但移植物的早期血管化仍是制约其疗效的瓶颈问题。课题组前期证实BMSCs（骨髓间充质干细胞）和ECs（内皮细胞）协同调节缺损部位微环境，加速血管新生。申请人近期发现BMSCs诱发ECs骨架重塑并增强其迁移和成血管能力。TMT定量蛋白组学和预实验表明BMSCs来源的外泌体Nidogen-1（巢蛋白1）是关键效应分子。文献和前期结果提示其可能通过整合素介导的FAK/Rho-GTP信号发挥作用。据此，本项目拟通过体外共培养和体内成血管、骨缺损修复等实验，旨在：1）验证Nidogen-1对ECs成血管的调控作用；2）筛选Nidogen-1的整合素受体，明确FAK/Rho-GTP通路与血管再生的关系；3）评价Nidogen-1在组织工程骨血管化和骨修复中的应用效果。本研究将为组织工程移植物的血管化策略提供新靶点和新思路。

The repairment of large segmental bone defects is one of the giant challenges in orthopaedics. Tissue engineering techniques have offered promising approaches for treatments of bone defects. However, early vascularization of the graft is still a bottleneck restricting bone regeneration. Our previous study confirmed that BMSCs (bone marrow mesenchymal stem cells) and ECs (endothelial cells) regulated the microenvironment of bone defect regions synergistically and accelerated neovascularization. Recently, we further found that BMSCs induced skeleton remodeling of ECs, and enhanced their migration and tube formation. Moreover, the data of TMT proteomics and in vitro experiments supported BMSCs derived exosome Nidogen-1 as a key modulator. Both the previous studies and our preliminary results suggested that Nidogen-1 regulated vascularization of ECs via intergrin-mediated FAK/Rho-GTP signaling pathway. Accordingly, this project, performed with in vivo and in vitro experiments, intends to confirm the regulation of exosome Nidogen-1 on endothelial vascularization firstly, and further elucidate the role of FAK/Rho-GTP pathway in neovascularization mediated by Nidogen-1. At last, the effects of Nidogen-1 on vascularization and repairment of tissue engineered bone will be evaluated. This research aims to provide a newsight for the construction and application of early vascularized tissue engineered grafts.