骨缺损修复是骨科面临的十分棘手的挑战。若能根据骨修复的需求，调控骨髓间充质干细胞(BMSCs)的增殖、定向分化及骨缺损周围血管的形成，即可促进骨缺损的修复、愈合。我们前期研究证明，Notch通路可以调控BMSCs的增殖与分化, Cell Sheet作为组织工程骨膜可以促进结构性异体骨修复骨缺损。近期报道，甲状旁腺素(PTH)不仅可以促进骨折愈合，而且可以促进骨活跃区的血管生成，但其调控机制尚不明确。因此，我们拟在体外靶向Notch配体Jagged1激活BMSCs Notch通路，获取稳定扩增、维持分化潜能的BMSCs，培养成Cell Sheet, 探讨靶向激活Notch通路的Cell Sheet作为组织工程骨膜联合PTH促进异体骨修复骨缺损的作用及分子机制。同时，通过体内、体外实验，明确和归纳PTH调控骨重建过程中血管形成与分布的机制。本课题为骨缺损修复的研究及治疗提供了崭新的思路和方法。

Critical sized bone defects is still a major challenge in the field of orthopaedic surgery. Theoretically，if the chondrogenic, osteogenic and angiogenesis property of bone-marrow derived stromal cells (BMSCs) could be enhanced in the bone remodeling, bone defect healing during skeletal repair can be promoted. In our previous study, we illustrate the ability of BMSCs sheets to act as an engineered periosteum that promotes bone callus formation during allograft healing and integration in a preclinical mouse model of critical sized femoral allograft. Additionally, it is reported that intermittent PTH could increase not only the bone mass but also small vessels in the sites of new bone formation, but the biology mechanisms by which PTH induced angiogenesis remain unclear. Therefore，our study try to determine whether transient Jagged1-mediated NOTCH signaling could promote human BMSCs (hBMSCs) maintenance and expansion in vivo, while preserving their skeletogenic differentiation capacity, and explore the effect of allografts wrapped with NOTCH-mediated hBMSCs Sheet combined with PTH on the allograft healing. Specially, both vitro and vivo experiments will be conducted to clarify the molecular and signaling mechanism underlying the role of PTH on angiogenesis in the process of bone healing. The accomplishment of our study will provide a favorable approach and insight for the treatment of massive allograft healing.