腱-骨连接处是由梯度渐变的肌腱、纤维软骨、矿化纤维软骨和骨等组织构成，其发病率高且再生修复困难，使腱-骨愈合成为运动医学中的一大难题。支架的拓扑结构既能影响种子细胞的分化，又能调节巨噬细胞的极化，但鲜有研究关注两者的相互作用。基于此，本课题创新性地以巨噬细胞极化为切入点，提出了支架的取向性与巨噬细胞共同影响肌腱干细胞（TSCs）的分化及后续功能。据此，本课题拟通过反向旋转挤出技术制备不同取向的胶原纤维支架（CMs），首先研究取向性CMs对巨噬细胞极化状态的影响；再以CMs诱导的分泌物作为条件培养基，探究巨噬细胞极化对TSCs分化的影响。最后，体内考察CMs的炎症功能调节作用和分级取向支架的腱-骨愈合效果，全面解析仿生支架、巨噬细胞极化以及TSCs分化三者的相互作用。本项目的成功实施将极大地丰富仿生支架与腱-骨组织相互作用的研究内容，为腱-骨组织工程理想支架的制备提供了一条新的途径。

The healing of injured tendon-bone insertions, remains a formidable challenge due to the gradient regions which consist of tendon, fibrocartilage calcified fibrocartilage and bone tissues, and are featured with high incidence and difficulty in regeneration. It has been widely shown that the topography of scaffolds can affect cell differentiation and also affect macrophage polarization. However, few attentions have been paid to their interactions. Therefore, this project innovatively proposed that fiber orientations of the scaffold and macrophage polarization from them will affect the differentiation of tendon stem cells (TSCs) and even their subsequent functions. To realize this goal, we employed counter-rotating extrusion technology to fabricate collagen fiber membranes (CMs) of various orientations. The effects of various CMs on the macrophage polarization are first investigated. Then, CMs - induced secretion was used as the conditioned medium to investigate the effect of macrophage polarization on TSCs differentiation. Finally, the in-vivo inflammatory regulation of CMs and the in-situ repair of tendon-bone by scaffolds with graded orientations are further investigated. And the interactions among biomimetic scaffolds, CMs-induced macrophage polarization and TSCs differentiation are comprehensively analyzed. The success of this project will expand the scope of biomimetic scaffold and tendon-bone, and provide a new approach to construct scaffolds for tendon-bone tissue engineering.