Hongbo Fei, Zhuoran Wang, Yujiao Li, Hongchen Sun, Xiuping Meng, Hongbing Lin
Periodontitis, a chronic inflammatory disorder, results in tooth loss and adversely affects oral and systemic health. Current therapies fail to effectively regenerate bone loss caused by inflammation. Human stem cell-derived exosomes have emerged as important mediators of tissue regeneration and inflammation modulation in periodontitis, yet their clinical use faces ethical and technical challenges. Non-human-derived exosomes present a viable alternative, leveraging their ability to enhance tissue repair, reduce inflammation, and stimulate regeneration. This review synthesizes recent advances (2020-2025) in non-human-derived exosome applications, emphasizing their roles in immunomodulation, angiogenesis, and periodontal regeneration, while evaluating clinical translation prospects.