Abstract

Objectives: To evaluate the repair effect of adipose-derived mesenchymal stem cells (ADSC-EVs) on birth trauma, and to explore its application potential as an innovative regenerative strategy for vaginal laxity patients. In light of the current clinical demand for minimally invasive regenerative therapies in the fields of aesthetic and functional gynecology, this study further explores the translational prospects of EVs in early intervention and tissue repair. Introduction: Childbirth-associated mechanical stress is the pathological basis for vaginal laxity. Our previous study confirmed the presense of ECM disintegration in the vaginal wall of Simulated Birth Injury (SBI) rats, which reduced tissue tensile strength, and elasticity..ADSC-Evs are rich in various bioactive molecules and circumvent risks associated with cell transplantation, . This study evaluates the therapeutic effects and mechanisms of PEG hydrogel-loaded ADSC-EVs in SBI rat, providing preclinical evidence for regenerative therapies and aesthetic translational applications for vaginal laxity. Materials / method: Primary human vaginal fibroblasts and rat ADSCs were isolated and cultured. ADSC-EVs were harvested ,An SBI rat model was established using transurethral vaginal balloon dilation for 2 hours. Rats were then randomly divided into four groups receiving local injections of: PBS, blank hydrogel, free ADSC-EVs, or PEG@EVs hydrogel. Vaginal wall tissues were collected 7 days post-modeling for comprehensive histological (Masson's trichrome, EVG staining), immunohistochemical, and molecular analyses. Results: Analysis revealed that mechanical injury significantly induced oxidative stress, ECM disorganization, and inflammatory activation in pelvic floor tissues. Hydrogen peroxide induced ROS accumulation, apoptosis, mitochondrial damage, and ferroptosis in vaginal fibroblasts, while simultaneously suppressing collagen I and III expression and upregulating MMP2 and MMP9. ML385 substantially attenuated the protective effects of the EVs. Conclusion: ADSC-EVs effectively counteract these pathological processes and significantly improve the injuries, thereby offering potential therapeutic benefits for pelvic floor dysfunction disorders such as vaginal laxity. This research not only deepens the understanding of pelvic floor injury mechanisms but also aims to provide a solid scientific foundation for the future development of a minimally invasive, highly effective treatment for vaginal laxity and rejuvenation.