肩袖损伤发病率较高且临床治疗效果需进一步提高。近年来很多研究者尝试使用蚕丝组织工程肌腱来促进肩袖的修复，但是蚕丝支架在体植入以后力学丢失过快，导致修复效果不佳。申请人前期研究发现，蚕丝支架周围侵入的巨噬细胞M1活化是导致蚕丝力学丢失的主要原因。我们推测不同的巨噬细胞亚型，对于蚕丝力学的丢失以及组织的长入会产生不同的效应；通过调控巨噬细胞的亚型，可以调控蚕丝在体的力学丢失和组织长入速度，实现肩袖损伤组织的快速再生。随后我们证实，蚕丝支架中载荷胰岛素样生长因子（IGF-1）能促进巨噬细胞从M1向M2亚型转变。本项目拟进一步通过体内和体外研究，阐明蚕丝支架中载荷IGF-1，能促进巨噬细胞表型转换，延缓蚕丝支架的力学丢失，促进肌腱组织的长入；并深入阐明IGF-1激活PI3K/AKT信号通路的分子机制。本项目将构建出一种可以兼顾力学稳定性以及组织长入，具有临床转化潜能的新型肩袖蚕丝支架。

Rotator cuff injury is a common clinical disease and the clinical treatment effect needs to be further improved.. In recent years, many researchers have begun to use silk tissue engineering tendons to promote the repair of rotator cuffs. However, the mechanical loss of the silk scaffold after implantation is fast, which is a problem that needs to be solved before the clinical transformation of tissue engineering tendon/ligament. In our early study, we confirmed that M1 macrophages around silk fibers are mainly responsible for the mechanical loss of the silk scaffold after implantation. We speculate that different macrophage subtypes have different effects on silk mechanics loss and tissue ingrowth. By regulating the subtypes of macrophages, it is possible to regulate the mechanical loss of silk and the rate of tissue ingrowth, and achieve rapid regeneration of rotator cuff injury tissue. Subsequently, we confirmed that the loading of insulin-like growth factor (IGF-1) in silk scaffolds can promote the transformation of macrophages from M1 to M2 subtype. This project intends to further clarify the molecular mechanism how IGF-1 loaded in the silk scaffold can promotes the phenotypic transformation of macrophages, delays the mechanical loss of the silk scaffold, and promotes the molecular mechanism of the growth of tendon tissue, and clarified the molecular mechanism of IGF-1 activation of PI3K/AKT signaling pathway. This project will construct a new type of IGF-1 sustained-release silk scaffold that can balance mechanical stability and tissue growth, which provides new possibilities for the design and clinical transformation of silk tissue engineering scaffolds.