乳腺癌骨转移是女性生命的重要威胁，其机理尚不明晰。我们推测癌细胞骨转移的部位与骨微环境中的微纳结构及其组装有关。基于自然骨多级有序的结构，其工程化体外模型一直难以构建。本项目基于组织工程和生物矿化的基本原理，以自组装胶原纤维为模板，细胞为矿化加工主体，形成具有特定微纳结构的矿化胶原细胞外基质；同心卷轴或层层叠加构建多级有序微纳结构的3D骨微环境。并以此为模型，采用成骨细胞、破骨细胞和乳腺癌细胞多细胞培养体系，从细胞生物学和分子生物学角度开展乳腺癌骨转移研究，探讨骨组织中多级有序微纳结构对乳腺癌骨转移的影响极其相关机制。开展特征微纳结构的动物骨体外模型研究，分析工程化模型和动物骨模型的一致性和差异性，了解乳腺癌骨转移与人体解剖部位的相关性，为乳腺癌治疗提供理论依据；并在一定程度上完善癌细胞归巢的结构因素。

Bone is the most common site of metastasis for breast cancer, however the reasons for this remain unclear. We hypothesise that the parts of breast cancer metastasis would be related to the micro/nano structure and its hierarchical assembed orgnization of bone microenvironment.Due to a hierarchical structure of nature bone, engineered in vitro model as breast cancer metastasis is difficult to be constructed. Base on the principle of tissue engineering and biomineralization, extracellular matrix maninly containing aligned mineralized collagen fiber will produced by the mineralization of osteoblast on self-assembled collagen fiber template. A three-dimensional tisse engineered bone microenvorinment with hierarchical micro/nano structure is to be constructed via layer-laryer rolling-up or overlying. In the model, tri-culture of oseteoblast, osteoclast and MDA-AB-231 will be developed in order that the study of breast cancer metastasis to bone will analysis from views of Cell biology and molecular biology. The effctes of the hierarchical micro/nano structure of bone microenvorinment on breast cancer metastasis to bone are to dectect and its related mechanism is to be analysised. Animal bone model also is designed to the study of breast cancer metastasis for the consistency and otherness between animal bone model and engineered model will be discussed, further the correlation between parts of body and cancer metastasis will be predicted for the breast cancer treatment. The results also will provide information about the effect of architecture on cancer cell homming.