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The impact of extracellular vesicles derived from adipose\u2010derived mesenchymal stem cells (ADSC\u2010EVs) on pelvic floor tissue injury remains unclear. Due to their short half\u2010life and rapid clearance in vivo, ADSC\u2010EVs lose efficacy quickly. To address this, an injectable tetra\u2010PEG hydrogel to encapsulate ADSC\u2010EVs (PEG@EVs) is developed. The hydrogel is formed by tetra\u2010PEG\u2010NH<jats:sub>2<\/jats:sub> and tetra\u2010PEG\u2010NHS through an ammonolysis reaction, leading to the formation of amide bonds within seconds. Vaginal wall tissue from POP patients shows disruption in the extracellular matrix, lipid peroxidation, and inflammation. In vitro, ADSC\u2010EVs significantly reduce H\u2082O\u2082\u2010induced oxidative stress, lipid oxidation, and apoptosis, while enhancing the expression of Nrf2 and its downstream targets\u2014CAT, NQO1, HO\u20101, and SOD2. ADSC\u2010EVs also upregulate GPX4 and SLC7A11, reducing mitochondrial damage and mitigating ferroptosis. The Nrf2 inhibitor ML385 reverses these protective effects. In a rat model of childbirth injury, PEG@EVs treatment promotes Nrf2 nuclear translocation, induces the M1\u2010to\u2010M2 macrophage conversion, reduces inflammation, and stimulates collagen deposition, thereby accelerating vaginal wall repair. The findings of this study may serve as a foundation for early targeted intervention in POP, representing a promising therapeutic approach.<\/jats:p>","DOI":"10.1002\/adhm.202405259","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T06:10:56Z","timestamp":1744783856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Extracellular Vesicles from Adipose\u2010Derived Mesenchymal Stem Cells Combined with PEG Hydrogel Alleviate Maternal Simulated Birth Injury in a Rat Model"],"prefix":"10.1002","volume":"14","author":[{"given":"Qing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Peking University People's Hospital  No.11, Xi\u2010Zhi\u2010Men South Street, Xi Cheng District Beijing 100044 China"},{"name":"Pelvic Floor Disorders Research Center of Peking University Health Science Center  Beijing 100044 China"},{"name":"Research 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