Yue Su, Yinyi Song, Fan Xue, Hanbing Wang, Zitong Zeng, Yourong Jiang
Oral submucous fibrosis (OSF) is a chronic, potentially malignant oral mucosal disease driven by areca nut chewing. It is characterized by progressive collagen deposition and debilitating symptoms such as trismus and burning sensation, which severely impair quality of life and confer a risk of malignant transformation. Given the limited efficacy of current therapies, this review aims to provide a comprehensive and critical appraisal of the evolving therapeutic landscape for OSF. We summarize conventional strategies, including pharmacological, surgical and physical approaches, alongside emerging therapeutic strategies, through a comprehensive literature review and screening of historical periodicals. The analysis reveals that established treatments have inherent limitations, whereas emerging approaches, including biomaterial-based delivery systems, nucleic acid and cell-based therapies, drug-loaded microneedle patches, and preventive interventions, show promise by overcoming poor mucosal retention, limited epithelial penetration and rapid salivary clearance. Mechanistic insights and the therapeutic potential of these strategies are discussed based on preclinical evidence. We conclude that current OSF therapies have limited efficacy, underscoring the need for innovative approaches. Emerging biomaterial-based systems and targeted drug delivery hold substantial potential, but further clinical research is essential to validate their safety and effectiveness for patient care.