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揭示宫腔粘连的病理图景:机制洞察与外泌体-生物材料治疗创新

Unveiling the Pathological Landscape of Intrauterine Adhesion: Mechanistic Insights and Exosome-Biomaterial Therapeutic Innovations.

作者信息

Qin Zhimin, Yu Qicheng, Long Yan

机构信息

Department of Obstetrics and Gynecology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.

Emergency Department of Xuanwu Hospital, Capital Medical University, Beijing, 100053, People's Republic of China.

出版信息

Int J Nanomedicine. 2025 Aug 5;20:9667-9694. doi: 10.2147/IJN.S527637. eCollection 2025.

Abstract

Intrauterine adhesion (IUA) is a fibrotic disorder caused by endometrial injury, characterized by structural damage and functional impairment of the endometrium, which severely impacts female reproductive health. The core pathology of IUA revolves around aberrant fibrosis, driven by intricate interactions among inflammation, epithelial-mesenchymal transition (EMT), and dysregulated cellular processes such as autophagy and ferroptosis. Inflammation acts as a pivotal initiator, directly activating fibrotic pathways or inducing EMT, thereby exacerbating fibrosis. Recent studies highlight the dual roles of autophagy and ferroptosis in IUA progression, where their dysregulation either mitigates or aggravates fibrotic outcomes, underscoring the complexity of its pathogenesis. Current treatments, such as transcervical resection of adhesions (TCRA), offer short-term anatomical restoration but fail to address high recurrence rates and insufficient endometrial regeneration. Exosomes have emerged as a promising cell-free therapeutic strategy, leveraging their bioactive cargo to modulate fibrosis, inflammation, and EMT. However, research on exosome-based therapies for IUA remains limited, particularly in targeting autophagy, ferroptosis, and their integration with biomaterials. Biomaterial-assisted exosome delivery systems, such as hydrogels and scaffolds, enhance therapeutic efficacy by enabling sustained release and localized action. Despite preclinical progress, clinical translation faces challenges, including standardized protocols and long-term safety validation. This review synthesizes the pathological mechanisms of IUA, explores the therapeutic potential of exosomes and biomaterials, and discusses future directions to bridge the gap between mechanistic insights, therapeutic strategy development and clinical applications.

摘要

宫腔粘连(IUA)是一种由子宫内膜损伤引起的纤维化疾病,其特征是子宫内膜的结构破坏和功能受损,严重影响女性生殖健康。IUA的核心病理围绕异常纤维化展开,由炎症、上皮-间质转化(EMT)以及自噬和铁死亡等细胞过程失调之间的复杂相互作用驱动。炎症作为关键的启动因素,直接激活纤维化途径或诱导EMT,从而加剧纤维化。最近的研究强调了自噬和铁死亡在IUA进展中的双重作用,它们的失调要么减轻要么加重纤维化结果,凸显了其发病机制的复杂性。目前的治疗方法,如宫腔镜粘连切除术(TCRA),可提供短期的解剖结构恢复,但无法解决高复发率和子宫内膜再生不足的问题。外泌体已成为一种有前景的无细胞治疗策略,利用其生物活性成分来调节纤维化、炎症和EMT。然而,基于外泌体的IUA治疗研究仍然有限,特别是在针对自噬、铁死亡及其与生物材料的整合方面。生物材料辅助的外泌体递送系统,如水凝胶和支架,通过实现持续释放和局部作用来提高治疗效果。尽管临床前取得了进展,但临床转化面临挑战,包括标准化方案和长期安全性验证。本综述综合了IUA的病理机制,探讨了外泌体和生物材料的治疗潜力,并讨论了未来的方向,以弥合机制见解、治疗策略开发和临床应用之间的差距。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0779/12335249/e3fe92fa43c9/IJN-20-9667-g0001.jpg

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