TSG6‐Exo@CS/GP Attenuates Endometrium Fibrosis by Inhibiting Macrophage Activation in a Murine IUA Model

Abstract

Intrauterine adhesion (IUA), commonly known as Asherman's syndrome, is a disease characterized by the formation of fibrous scar tissue within the uterine cavity, which can lead to severe clinical complications and significantly compromise the reproductive health and fertility of women. Unfortunately, severe cases of IUA currently lack effective treatment. This study presents a novel approach that utilizes TSG6‐modified exosomes (Exos) in conjunction with an injectable thermosensitive hydrogel (CS/GP) to mitigate the occurrence of IUA by reducing endometrium fibrosis in a mouse IUA model. The findings of this study demonstrate that TSG6‐modified Exos effectively inhibit the activation of inflammatory M1‐like macrophages during the initial stages of inflammation and maintains the balance of macrophage phenotypes (M1/M2) during the repair phase. Moreover, TSG6 inhnibits the interaction between macrophages and endometrial stromal fibroblasts, thereby preventing the activation of stromal fibroblasts into myofibroblasts. Furthermore, our research indicates that CS/GP facilitates the sustained release of TSG6‐modified Exos, leading to a significant reduction in both the manifestations of IUA and the extent of endometrium fibrosis. Collectively, through the successful construction of CS/GP loaded with TSG6‐modified Exos, we have achieved a reduction in the occurrence and progression of IUA by mitigating endometrium fibrosis. Consequently, this approach holds promise for the treatment of IUA.This article is protected by copyright. All rights reserved