大段骨缺损与人工置换、脊柱融合等对骨修复材料的临床需求量十分巨大。但目前材料与宿主相互作用在骨形成过程中的关键调控机理并不完全清楚。一些文献和我们前期工作表明，细胞应激与稳态维持的关键调控基因与相关信号通路对成骨分化具有调控作用。我们提出“骨修复材料植入早期应激与稳态维持过程中miRNAs和DNA甲基化等表观遗传学机制参与了对骨形成的调控作用”假设。本项目结合生物学与材料学技术方法，重点研究应激与稳态维持的重要转录因子对干/祖细胞生存、增殖与分化的相关miRNAs调控作用。探讨miRNAs调控网络介导不同信号通路之间交叉串话的机理，以揭示细胞应激与稳态机制及其对迁移至材料中骨形成细胞生存、增殖与分化的调控机理。本项目如能成功实施将助于阐明生物材料与宿主相互作用的生物学机制，不仅可为生物活性骨修复材料的设计提供理论依据，并可设计制备具有生物活性且更适合临床的骨修复材料。

The clinical demands of bone repair materials are huge for massive bone loss, artificial bone replacement and spinal fusion. However, it is not entirely clear to understand the key regulatory mechanisms of interaction between bone repair materials and host in the process of bone regeneration. Literatures and our previous study suggested that some key regulatory genes and signaling pathways of cellular stress response and homeostasis are associated with the regulation of osteoblastic differentiation. We put forward the hypothesis that the epigenetic mechanisms such as DNA methylation and miRNAs are involved in the regulation process of bone formation during cellular stress response and homeostasis in the early phase of bone repair materials implantation. The project, using scientific technology and methodology from biology and biomaterials, focuses on relevant miRNAs to control cellular stress response and homeostasis of stem/progenitor cells for cell survival, proliferation and differentiation. We investigate the mechanisms of miRNAs regulatory networks mediated crosstalk between different signaling pathways in the regulatory mechanism of cellular stress response and homeostasis when stem/progenitor cells are migrated into materials. The successful implementation of the project will help to elucidate the biological mechanisms of interactions between host and biological materials. We will provide a theoretical basis in the design of bioactive bone repairing materials for more suitable bone repair materials for clinical use.