股骨头坏死（ONFH）发病率高、后果严重，且存在持续性恶化问题，至今机制不清、治疗困难。已知ONFH均伴有缺血缺氧，缺血缺氧可直接导致组织坏死，而组织坏死又会加重缺血缺氧。在ONFH区域诱导血管再生非常困难且再生速度太慢，故该策略的治疗效果并不好。结合我们在可控释氧和骨组织工程的工作基础及文献调研，本课题假设如下：通过可控释氧组织工程能打破ONFH局部“坏死/缺氧”的恶性循环，也可促进种子细胞存活；联合移植的成骨细胞和内皮祖细胞可分别促进新骨质形成以代偿坏死骨组织以及促进血管新生以尽快恢复供血供氧。本课题首先将通过体内外实验探明缺氧在ONFH发生与发展中的作用及相关机制，为通过供氧或调控缺氧相关信号通路防治ONFH提供依据；进而联合可控释氧材料与干细胞源性成骨细胞和内皮祖细胞探索新型组织工程技术治疗ONFH，希望从预防和治疗两个方面为解决ONFH的持续恶化和治疗困难的问题提供新策略。

The osteonecrosis of femoral head (ONFH) is a serious clinical problem which tends to aggravate continuously and has no effective therapeutic strategies up to now. It is well known that the ONFH is accompanied by ischemia and hypoxia. Ischemia and hypoxia can directly lead to tissue necrosis, which in turn aggravates ischemia and hypoxia. Due to the angiogenesis in the necrotic areas of femoral head is difficult and slow, the treatment effect of targeting vascular regeneration is not satisfactory. Based on our previous works on the controlled oxygen releasing biomaterials(CORB) and bone tissue engineering, we draw a hypothesis for this project: delivering CORB into the ONFH can break the vicious circle of necrosis/hypoxia which may alleviate the necrotic process and improve the survival rate of seeding cells. The seeding cells of osteoblasts and endothelial progenitor cells can facilitate osteogenesis and angiogenesis by which to replace the lost bone tissue and rebuild the blood supply as soon as possible. For this purpose, the potential roles of hypoxia in the occurrence and development of ONFH and its related mechanisms will be explored through in vivo and in vitro experiments. Furthermore, a novel tissue engineering strategy for treating ONFH will be developed by combining CORB and double-seeding cells (stem cell-derived osteoblasts and endothelial progenitor cells). Overall, present project aims to illustrate the role of hypoxia in the ONFH and explore a prospective strategy for treating ONFH by preventing the deterioration as well as accelerating the recovery.