Development of polypeptide scaffold for anti-endometrial invasion and ordered myometrial recovery in uterine diverticulum.

Uterine diverticulum (UD) is characterized by localized thinning of the uterine myometrium, leading to the formation of recessed structures. While its mechanisms remain undefined, UD, often an aftermath of cesarean sections, mandates subsequent surgical intervention, highlighting the critical need for intraoperative prevention. Drawing inspiration from the natural anatomical structure of the uterus, we developed biomimetic, anisotropic, multi-channel silk fibroin-based uterine bioscaffolds (BSBs). The BSBs, characterized by aligned fibrous structures and hollow channels, significantly promoted the orderly directional growth of uterine smooth muscle cells and enhanced the infiltration of human umbilical vein endothelial cells. Single-cell RNA sequencing (scRNA-seq) analysis of endometrial tissue affected by UD suggested that ectopic invasion of the endometrial tissue might contribute to UD formation. The BSBs incorporated bioactive polypeptides identified through scRNA-seq with exosomes derived from autologous menstrual blood stem cells, creating a composite scaffold (BSBs@exo@poly) designed to avert UD onset. In a rat model of uterine injury, treatment with BSBs@exo@poly effectively suppressed ectopic endometrial tissue invasion, guided the organized reconstruction of muscle fibers, and supported endometrial regeneration, thereby accelerating the restoration of normal uterine morphology and attenuation of inflammation. Therefore, BSBs@exo@poly presents an innovative and promising therapeutic strategy for the treatment of uterine damaged conditions.