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

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.